A five-year-old boy presented to our emergency department with severe posterior neck pain that was exacerbated upon neck movement. Cervical spine radiography revealed calcification in the cervical intervertebral disk 3–4.Pediatric idiopathic intervertebral disk calcification is a benign, rare condition that might be complicated by associated severe neurological symptoms. In this case, the symptoms gradually subsided with conservative management alone. A five-year-old male with a history of asthma presented with complaints of neck pain that had persisted for one month. The pain exacerbated on bowing or exercising. Physical examination revealed that pain was elicited on performing neck movements, especially flexion-extension; neurological symptoms were not noted. Cervical spine radiograph was obtained .Pediatric idiopathic intervertebral disk calcification (PIIVDC) is a rare cause of neck pain in children, especially boys, 5–12 years of age, and is attributed to calcification of the intervertebral disks.2Neurological complications develop when the calcification herniates and compresses the nerve root or spinal cord.What do we already know about this clinical entity?Pediatric idiopathic intervertebral disk calcification (PIIVDC) is a benign, rare condition with unclear etiology.What is the major impact of the image(s)?PIIVDC is easily diagnosed with a plain radiograph. We should consider cervical spine radiograph as the initial test for children with neck pain.How might this improve emergency medicine practice?Emergency physicians should consider PIIVDC in their differential diagnosis of children with neck pain.


Pseudoaneurysm formation is known to complicate arteriovenous haemodialysis access. Ultrasound guided thrombin injection is a recognised treatment option, but is not possible in pseudoaneurysms with no measurable neck. Balloon assisted techniques have been described in such cases, which transiently obstruct flow out of the pseudoaneurysm and thereby prevent non-target embolization during ultrasound guided percutaneous thrombin injection. We describe a balloon assisted technique for the treatment of a radial artery pseudoaneurysm, via retrograde access from the draining cephalic vein of an arteriovenous fistula.A 61-year-old male with a radio-cephalic fistula was found on duplex ultrasound to have a large radial artery pseudoaneurysm with no measurable neck, as well as a juxta-anastomotic cephalic vein stenosis. Endovascular treatment was selected over open surgery. Retrograde cephalic venous access was established, which allowed for concurrent treatment of both the venous stenosis and the arterial pseudoaneurysm. After balloon dilation of the juxta-anastomotic stenosis, a percutaneous transluminal angioplasty balloon catheter was advanced across the arteriovenous anastomosis and inflated across the neck of the radial artery pseudoaneurysm, to transiently obstruct blood flow. This allowed for safe injection of thrombin into the pseudoaneurysm by direct ultrasound guided sac puncture; thereby achieving thrombosis.Balloon assisted ultrasound guided thrombin injection is an endovascular treatment option that can obviate the need for open surgery in cases involving pseudoaneurysms with no measurable neck. The technique described allowed both concurrent treatment of a juxta-anastomotic venous stenosis and treatment of an arterial pseudoaneurysm from a single venous puncture. This technique avoided arterial access and its inherent complications. Pseudoaneurysm formation is a recognised complication affecting arteriovenous haemodialysis access. Cases that are not suitable for open surgical repair are often treated with minimally invasive techniques including ultrasound guided thrombin injection (UGTI) , using balloon-assisted UGTI with retrograde access from the cephalic vein draining the AVF. The procedure was undertaken on an outpatient basis, concurrently with venoplasty to treat a juxta-anastomotic cephalic vein stenosis.A 61-year-old male with a left radio-cephalic fistula presented with a low haemodialysis flow rate of 270ml/min; measured using a Transonic® flow-QC device . Duplex ultrasound (DUS) demonstrated a 24mm diameter pseudoaneurysm arising directly from the radial artery. Whilst the neck of the pseudoaneurysm was narrow, there was no measurable neck length, increasing the risk of non-target embolization with standard thrombin injection techniques , with good angiographic result.A 7 × 40mm Sterling Balloon (Boston Scientific) was then advanced over the wire and positioned across the neck of the pseudoaneurysm under ultrasound guidance. The balloon was sized to match the diameter of the radial artery, which measured 7mm on DUS. The pseudoaneurysm was punctured with a 21-guage needle under ultrasound guidance. The 7 × 40mm Balloon was then inflated, covering the pseudoaneurysm neck. 2mls of Thrombin was injected under ultrasound guidance, filling the pseudoaneurysm. The balloon was then deflated.After balloon deflation, DUS demonstrated a small amount of residual perfusion within the largely thrombosed pseudoaneurysm sac. This appeared to have resolved following ultrasound guided manual compression of the pseudoaneurysm. Follow up DUS 72 h later demonstrated a persistent 8mm area of perfusion within the pseudoaneurysm. A repeat procedure was therefore undertaken, employing the same technique as the initial procedure, requiring a further 1mls of thrombin to achieve complete thrombosis.No complications occurred during or immediately after either procedure. Both procedures were undertaken as day cases. A follow up ultrasound scan 72 h after the second procedure demonstrated complete thrombosis of the pseudoaneurysm with volume flow of 1400mls/min recorded in the brachial artery Fig. . SuccessWe present a case of a radial artery pseudoaneurysm treated with balloon assisted UGTI with retrograde venous access via an ipsilateral radio-cephalic AVF. Whilst balloon assisted techniques for pseudoaneurysm embolization have been described previously (Mary et al. Our patient presented due to low haemodialysis flow and it is likely that resultant venepuncture difficulties caused the pseudoaneurysm, which lay immediately deep to the venous needling site. The position of the pseudoaneurysm also left it susceptible to further injury from inadvertent puncture during subsequent AVF cannulation.The location of the pseudoaneurysm in the mid/upper forearm made open surgery a technically difficult, higher risk treatment option. The radial artery lies deep to pronator teres at this position and the draining cephalic vein directly overlying the pseudoaneurysm would have needed to be mobilised. The patient also wished to avoid an overnight admission due to social circumstances.Treatment with a covered stent was considered and would have been attempted had balloon-assisted thrombin injection failed. The endovascular approach via the draining vein of the AVF also allowed concomitant treatment of the juxta-anastomotic stenosis; improving flow within the fistula.Arterial pseudoaneurysms in patients with radio-cephalic AVFs have previously been treated with balloon assisted techniques via a retrograde puncture of the distal radial artery (Aytekin et al. Residual filling of the pseudoaneurysm was identified by DUS following the first attempt at Thrombin injection and a second procedure was required to achieve sustained thrombosis. DUS follow up post procedure is essential to ensure thrombosis with no re-perfusion. At the time of writing the patient continues to dialyse successfully with no further complications. Clinical surveillance continues with physical examination of the AVF and regular measurement of volume flow on dialysis.This case demonstrates the feasibility of treating AVF related arterial pseudoaneurysms with no measurable neck with balloon assisted UGTI. Venous access in these cases may be preferable as it allows for concurrent treatment of AVF stenoses and carries a low risk of puncture site complications. The technique is adaptable for different anatomy and type of AVF and offers a minimally invasive treatment option as an alternative to open surgery.


Gluten sensitivity can manifest with a spectrum of neurological dysfunction including ataxia, encephalopathy and neuropathy with or without associated coeliac disease (CD). Gluten sensitivity can also present with central nervous system (CNS) hyperexcitability and cortical myoclonus which is often accompanied with refractory CD. CNS hyperexcitability can also be associated with Glutamic Acid Decarboxylase (GAD) antibodies or much less commonly with Glycine Receptor Antibodies (GlyR-Abs) but the direct pathogenic roles of these antibodies remain debatable. We have previously reported a link between gluten sensitivity and anti-GAD associated ataxia which improves with the adoption of gluten-free diet. It is unclear if a similar link exists between gluten driven CNS hyperexcitability and the presence of GlyR-Abs. We report two cases of CD presenting with CNS hyperexcitability and associated GlyR-Abs. Apart from ataxia and cortical myoclonus, one patient had refractory CD and died from enteropathy-associated T-cell lymphoma. The other patient not only improved with strict gluten-free diet but also showed serological elimination of circulating GlyR-Abs. We conclude that there is an interaction between gluten sensitivity and GlyR-Abs-associated CNS hyperexcitability and in such patients gluten-free diet is an important therapeutic intervention. The elimination of GlyR-Abs by the adoption of gluten free diet suggests that these antibodies may represent an epiphenomenon rather than being directly implicated in the pathogenesis. Gluten sensitivity represents a spectrum of disorders triggered by the ingestion of gluten . The diaVarious neurological manifestations have been described in the context of gluten sensitivity the commonest of which are ataxia, neuropathy and encephalopathy . Other lStiff person Syndrome (SPS) is a rare autoimmune neurological disorder characterised by axial muscle stiffness and spasms, often accompanied by neuropsychiatric symptoms. SPS is usually associated with glutamic acid decarboxylase (GAD) antibodies found in 70% of cases . VariantWe have previously reported a significant overlap between gluten sensitivity and anti-GAD associated diseases. In our cohort of gluten sensitive patients we found anti-GAD antibodies to be present in a high proportion of patients who also displayed features of stiff person syndrome or ataxia , 11. FurBrain hyperexcitability is also seen in patients with gluten sensitivity with and without CD although patients with persistent cortical myoclonus tend to have refractory CD . It is uThis was a 72-year-old man with a past medical history of hypertension and immune mediated hypothyroidism. He first presented to secondary care with a history of weight loss. His biochemistry profile revealed iron deficiency anaemia, low vitamin D, low folate and normal vitamin B12. CD was suspected and serological testing showed positive tissue transglutaminase antibodies (TTG), gliadin antibodies and endomysium antibodies (EMA). Gastroscopy and duodenal biopsy confirmed villous atrophy, crypt hyperplasia and increased intra-epithelial lymphocytes consistent with CD. He commenced gluten-free diet. Six months later, he presented with worsening mobility and further weight loss and at that point he was noted to have marked ataxia and right facial myoclonus that was speech sensitive. He admitted that he was not adhering to a strict gluten-free diet.Neurophysiological assessment was undertaken with a Natus Quantum amplifier  at a sampling rate of 2048 Hz. The recording included a multichannel electroencephalography (EEG) and surface EMG polygraphy . Data were exported for quantitative EEG/EMG analysis in Spike 2 (version 8.12) software . Somatosensory evoked potential (SEP) recordings were also performed and the possibility of C-reflexes  was assessed with surface EMG electrodes from arms and legs based on previously published methods . The recFurther serological testing revealed positive GlyR-Abs (using a cell based assay) and negative GAD antibodies. Paraneoplastic antibodies were also negative. MRI spectroscopy was markedly abnormal with N-Acetyl-Aspartate to Creatinine (NAA/Cr) ratio of 0.67 from the superior vermis and 0.61 from the cerebellar hemisphere . Reduced NAA/Cr is indicative of cerebellar neuronal dysfunction. PET-CT imaging revealed no malignancy. His neurological symptoms continued to worsen. Further immunohistochemistry on the original duodenal biopsy showed clonal changes supporting a diagnosis of refractory CD type 2 but without any evidence of enteropathy associated lymphoma. The patient was started on budesonide and mycophenolate. Levetiracetam was tried for the myoclonus. He continued to deteriorate clinically primarily due to worsening ataxia and eventually required PEG feeding as well as becoming bed bound. A repeat duodenal biopsy showed enteropathy-associated T-cell lymphoma (EATL). At that point he was deemed unfit for chemotherapy and passed away in hospital shortly after from pneumonia. This was 1 year after his initial presentation.This was a 20-year old man who presented with 8-year history of progressive painful leg spasms and extreme fatigue. He experienced difficulty with running which he used to enjoy. He felt that his muscles were becoming increasingly stiff every time he went for a run. His family also noted cognitive slowing which interfered with his academic performance. Initial investigations by his General Practitioner showed him to be iron deficient. As a result, screening for CD revealed an extremely high level of TTG antibodies, EMA and gliadin antibodies. Duodenal biopsy confirmed CD and he started a gluten-free diet. He was referred to the Gluten sensitivity/neurology clinic in Sheffield UK. Examination revealed ataxic gait, increased tone and stiffness in both lower limbs with hyper-reflexia. He had exaggerated startle response. Imaging of the neural axis did not show any abnormality apart from reduced NAA/Cr ratio of 0.81 from the vermis. The ratio from the right cerebellar hemisphere was 0.9 .EEG/EMG polygraphy undertaken as described in the previous patient did not show evidence of cortically driven myoclonus from the right thigh on cross correlation analysis. There was no abnormality in the SEP study. Exaggerated startle response was noted following presentation of an unanticipated auditory stimuli. Blink reflex excitability studies (implemented as a semiquantitative assessment of brainstem excitability) while using a short inter-stimulus interval between a conditioning and a test stimulus after 160 ms were performed. Single square pulse electrical stimulation of the supraorbital nerve was delivered at 20–25 mA and a 0.2 s pulse width. The blink reflex study was noted to be abnormal with persistence of a well formed R2 component recorded following the test stimulus. This electrophysiological assessment is used as a semiquiantitative assessment of brainstem excitability .GlyR-Abs were positive and anti-GAD negative. After adopting a strict gluten-free diet he noticed gradual improvement in his symptoms. He was now able to run again and resume his academic career. After 2 years on strict gluten-free diet and normalisation of the gluten sensitivity-related antibodies his glycine receptor antibodies became negative. Repeat electrophysiology showed normalisation of the blink reflex study. Repeat brain image showed improvement of the NAA/Cr ratio from the vermis (from 0.81 to 0.88).We have previously identified a link between gluten sensitivity and anti-GAD associated SPS as well as anti-GAD ataxia , 11. HerEvidence of pathogenicity for these antibodies does exist. In vitro and in vivo studies have demonstrated that binding of GAD by anti-GAD antibodies suppresses GABA release with an epitope dependence, leading to the development of cerebellar ataxia, thus suggesting that GAD antibodies may be implicated in the pathophysiology of anti-GAD ataxia . SimilarA clinical spectrum of neurological disease associated with GlyR-Abs has been described . Indeed Brain hyperexcitability can be a prominent feature in some patients with CD and neurological dysfunction . This usWe conclude that a small number of patients with neurological manifestations of CD and in particular those with hyperexcitable brain syndromes may have GlyR-Abs. Gluten-free diet may be an effective therapeutic intervention in such patents. Such diet seems to also result in serological elimination of GlyR-Abs at least in one case reported here. Confirmation of this observation in a larger series would be desirable.


We report the case of a 78-year-old female patient who had a PASCAL device implanted for severe degenerative mitral regurgitation. Intraprocedural echocardiography revealed persistent severe mitral regurgitation due to device dislocation. Implanting another device was not possible. After 8 days, the device was explanted, and the valve was replaced with a biological prosthesis. The PASCAL device and resected mitral valve leaflets were sent for histopathological workup. Transcatheter mitral valve repair is an alternative to surgery in symptomatic patients with secondary mitral valve regurgitation (MR) who are at high risk or deemed inoperable. Transcatheter mitral valve repair is an alternative to surgery in symptomatic patients with secondary mitral valve regurgitation (MR) who are at high risk or deemed inoperable. Percutaneous treatment in degenerative MR is still debated . We presA 78-year-old female patient was diagnosed with severe symptomatic  degenerative MR with posterior prolapse and a flail leaflet in the P2 segment due to chordal rupture. Transthoracic echocardiography showed a calcified mitral annulus, a preserved left ventricular ejection fraction (62%) and no concomitant tricuspid regurgitation. The heart team recommended mitral valve surgery, but the patient refused the operation even though she had no comorbidities (EuroSCORE II 1.86%). She was offered transcatheter intervention with the PASCAL device. Implanting the device was technically uneventful; however, persistent severe MR was observed intraoperatively due to device-leaflet detachment  and Cytosorbents Corp. The other authors have nothing to disclose. Interactive CardioVascular and Thoracic Surgery thanks Lenard Conradi and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.


A 25-year-old woman presented to the emergency department with two weeks of crampy right-flank pain, and urinary urgency and frequency. She was found to have a staghorn calculus filling her entire right renal pelvis on computed tomography imaging.In contrast to ureteral calculi, staghorn calculi are more commonly observed in female patients and typically present with an indolent clinical course. A low threshold for imaging should be maintained, as prompt referral to urology for stone removal or treatment is necessary. Staghorn calculi have a high likelihood of leading to renal failure or urosepsis without treatment. A 25-year-old Hispanic female presented to the emergency department (ED) with two weeks of waxing and waning right-sided flank pain. She described the pain as a cramping discomfort that worsened over the two weeks and was only mildly relieved by acetaminophen. She also reported urinary frequency and urgency without dysuria or hematuria. Physical examination was notable for right upper quadrant and mild right costovertebral angle tenderness. Urinalysis showed nitrite negative, leukocyte esterase positive urine with 685 white blood cells per high power field, 53 red blood cells per high power field, and appreciable bacteria. A computed tomography (CT) from the ED revealed a right staghorn calculus with hydronephrosis along with left nephrolithiasis , 2.Staghorn calculi are the only type of renal stones more commonly observed in female patients as a result of their association with urinary tract infections.What do we already know about this clinical entity?Struvite calculi are composed of magnesium ammonium phosphate (struvite) and calcium carbonate-apatite and are caused by urinary tract pathogens.What is the major impact of the image(s)?This image depicts struvite calculi within the renal pelvis and calyces giving the characteristic “staghorn” formation for which these stones are also named.How might this improve emergency medicine practice?As these stones are notably more insidious in presentation, earlier recognition and urgent referral will hopefully result in better outcomes for patients.


This study examines spouses who are in a caregiving situation to discern how they influence each other’s health. Previous studies reported health concordance and cross-domain effects among caregiver and care-recipient dyads. However, it is less understood of the health dyadic relationships among spouses who are in a caregiving situation. No studies have specifically looked into the relationship between self-rated health (SRH) and cognitive functioning among spousal caregiving dyads over time. In this study we analyzed the longitudinal reciprocal relationships between SRH and cognitive functioning measured by the Telephone Interview for Cognitive Status among older adults and their spousal caregivers, and whether the relationship differed by whether husband or wife was the caregiver. Longitudinal data from the Health and Retirement Study (2010-2016) on 540 dyads were pooled and analyzed using structural equation modeling under an actor-partner interdependence model. Results revealed cognitive concordance among older spouses in which caregivers’ cognition is associated with care-recipients’ cognition subsequently . SRH concordance was not significant. Cross-domain results showed only one significant direction, that is, care-recipients’ cognition in the subsequent time was significantly correlated with caregivers’ SRH, regardless of whether husband  or wife  was the caregiver. Our study found that married couples in a spousal caregiving situation displayed cognitive but not overall health concordance, and cross-domain effects of caregiver’s SRH on spousal care recipient’s cognition subsequently. The reciprocal associations suggest that addressing and improving either partner’s physical health and cognition may benefit both dyad members.


With improved systemic therapy that has limited impact on the intracranial compartment, the incidence of brain metastasis (BM) from solid cancers is rising and negatively impacting patient’s overall survival (OS). Treatment varies based on presentation, however, for patients with <4 symptomatic BMs current clinical practice involves surgical resection followed by stereotactic radiosurgery (SRS) to the resection cavity. Post-operative SRS is associated with increased risk of leptomeningeal disease (LMD) and local recurrence in the follow-up period. We hypothesize that pre-operative SRS will decrease the incidence of LMD as well as local recurrence and increase patient’s OS by delivering a lethal dose of radiation to tumor cells before they are disturbed by surgical resection. In a Phase II clinical trial (NCT03398694) we are treating patients with 1–4 symptomatic BMs with pre-operative SRS while collecting DNA and RNA sequencing data from core and peripheral edges of the resected tumor to examine the genomic effects of SRS on tumor.Post-SRS resected tumor specimens were divided into two groups: ‘center’ and ‘periphery’ with respect to the center of SRS treatment with periphery within 50% isodose line. Previously resected untreated BMs were used as control. DNA and RNA were isolated from all samples for sequencing.Our initial analyses show that pre-treatment with SRS, results in significant genomic changes at DNA and RNA levels throughout the tumor, in both center as well as periphery. Furthermore, significant transcriptomic differences were noted among matched samples between the central and peripheral SRS locations implicating differential effect of SRS dosing within a tumor. Initial gene ontological analysis on non-small cell lung cancer samples demonstrated an overexpression of WNT and BMP signaling pathways . These pathways are typically involved in neuronal development, hinting that adaptation to the brain microenvironment was occurring post SRS treatment.


Pilonidal sinus is an acquired condition caused by irritation to the hair follicles at the natal cleft, presenting with an abscess or chronic infection. It is prevalent in young adults affecting their productive lifestyle with morbidities. There are varieties of treatment options; however, there is no consensus yet for the ideal procedure. Less invasive procedures have evolved to replace the traditional surgical techniques, which cannot significantly reduce the risks of recurrence and wound complications despite extensive surgeries. We aimed to assess the effect of fibrin glue as a primary treatment after cleaning the sinus in pilonidal sinus disease. We searched for articles from PubMed®, Ovid MEDLINE®, Ovid EMBASE®, and Cochrane CENTRAL. Six studies that included 336 patients in total were analyzed. Fibrin glue treatment in these studies reported a quicker return to normal activities postoperatively, a low rate of infection, and an acceptable rate of recurrence. Thus, fibrin glue seems beneficial in the management of pilonidal disease. However, further high-quality studies are essential to support and confirm this evidence. Future research should also evaluate its cost and implications in the ambulatory service. Although there is no precise etiopathogenesis for this disease, the hypothesis is related to the recurrent erosion of hair follicles at the natal cleft  OR ("fibrin"[MeSH Terms] OR "fibrin"[All Fields] OR "fibrins"[All Fields] OR "fibrine"[All Fields]) OR ("fibrinogen"[MeSH Terms] OR "fibrinogen"[All Fields] OR "fibrinogens"[All Fields] OR "fibrinogen s"[All Fields] OR "fibrinogene"[All Fields]) OR ("Fibrin Tissue Adhesive"[MeSH Terms] OR ("fibrin"[All Fields] AND "tissue"[All Fields] AND "adhesive"[All Fields]) OR "Fibrin Tissue Adhesive"[All Fields] OR "tissucol"[All Fields]) OR  OR "calcium chloride"[All Fields] OR "Fibrin Tissue Adhesive"[MeSH Terms] OR ("fibrin"[All Fields] AND "tissue"[All Fields] AND "adhesive"[All Fields]) OR "Fibrin Tissue Adhesive"[All Fields] OR "tisseel"[All Fields] OR "fibrinogen"[MeSH Terms] OR "fibrinogen"[All Fields] OR "fibrinogens"[All Fields] OR "fibrinogen s"[All Fields] OR "fibrinogene"[All Fields] OR "fibrinolysis inhibitor"[All Fields] OR "thrombin human"[All Fields] OR "thrombin"[MeSH Terms] OR "thrombin"[All Fields] OR "thrombin s"[All Fields] OR "thrombine"[All Fields] OR "thrombins"[All Fields]) OR ("Fibrin Tissue Adhesive"[MeSH Terms] OR ("fibrin"[All Fields] AND "tissue"[All Fields] AND "adhesive"[All Fields]) OR "Fibrin Tissue Adhesive"[All Fields] OR "tissel"[All Fields]) OR ("Fibrin Tissue Adhesive"[MeSH Terms] OR ("fibrin"[All Fields] AND "tissue"[All Fields] AND "adhesive"[All Fields]) OR "Fibrin Tissue Adhesive"[All Fields] OR "beriplast"[All Fields]) OR ("Fibrin Tissue Adhesive"[MeSH Terms] OR ("fibrin"[All Fields] AND "tissue"[All Fields] AND "adhesive"[All Fields]) OR "Fibrin Tissue Adhesive"[All Fields] OR "crosseal"[All Fields]) OR ("Fibrin Tissue Adhesive"[MeSH Terms] OR ("fibrin"[All Fields] AND "tissue"[All Fields] AND "adhesive"[All Fields]) OR "Fibrin Tissue Adhesive"[All Fields] OR "transglutine"[All Fields])) AND ) OR  OR "Pilonidal Sinus"[All Fields] OR  OR "pilonidal cyst"[All Fields]) OR )). Table Eligibility CriteriaBoth new and recurrent pilonidal sinus disease were considered in this study. We included articles that reported the outcome of fibrin glue as the primary treatment with the cleaning of the sinus. There was no limitation to the age of patients. Any brand of fibrin sealant, including fibrinogen or a mixture of fibrinogen and thrombin, was studied. The inclusion criteria were articles published within the last ten years (2011-2021), studies related to humans only, and those published in English. We excluded review articles, those published earlier than 2011, and non-English papers. Study Selection ProcessTwo authors independently identified records via databases, followed by the removal of duplicates. Titles and abstracts of studies were then screened. We excluded non-relevant documents. Reports of relevant themes were retrieved to assess their eligibility. We applied the eligibility criteria mentioned above to include great studies in our review. The opinion from the third author was sought when the agreement was not achieved between the two authors throughout the selection process. We also designed a data extraction form to collect the data from the included studies.Risk of Bias and Quality AssessmentWe included six observational studies assessed for bias using the Newcastle-Ottawa Scale (NOS). Two reviewers independently judged the risk of bias in each article. In addition, a discussion with the third author was performed for any variability in the risk of inclination between the two reviewers. ResultsOne hundred and twenty-six articles were retrieved from the searching of databases. Ninety-two duplicates were removed, leaving 34 papers. Six themes were non-relevant after screening the abstracts and titles; therefore, they were excluded from the review. Out of 28 reports, one report could not be recovered. We were able to retrieve 27 articles to be assessed for eligibility. With the careful consideration of inclusion and exclusion criteria, two authors independently assessed the remaining articles and selected six articles finally. This process can be seen in the PRISMA flow diagram, Figure We extracted the data from selected six articles. The demographics such as the author's name, year of publication, location of study, sample size, age, and the number of male patients are presented in Table Table DiscussionThe management of the pilonidal disease can be divided into operative and non-operative management . DespitePost-Procedural InfectionAlmost all of our included studies reported the rate of infection developed after the intervention. Smith et al. reported that the group treated with pit excision and fibrin glue (PEF) had a comparable infection rate managed by lateralizing flap procedure (LFP). The infection rate was seven percent in the group treated with LFP, whereas eight percent in the PEF group. Forty-one children with a mean age of 15 were included in this study. The sealant they injected was TISSEEL  [The comparative study by Saedon et al. evaluated the outcome of those who had cleaning the sinus tract obliterated by fibrin sealant with the other group who had excision of the sinus tract and primary closure. The sample size was 34, with an equal division between the two groups. Those managed with fibrin sealant revealed an infection rate of six percent, while those allocated to have excision and subsequent closure resulted in a 47% postoperative infection rate. There was an outstanding contrast in the infection rate among the groups with a p-value of 0.045. But this evidence was uncertain since the antibiotic was given before the procedure in some patients with infection .Hardy et al. also reported a low rate of infection, which was 11.1%. It was a retrospective study of new and recurrent pilonidal sinus disease in those aged 15-17. It investigated the effect of fibrin glue, TISSEEL, applied in the cleaned sinus tract without giving any prophylactic antibiotic . These studies described non-identical surgical procedures and the application of fibrin glue with diverse brands and volumes. Some of them comprised of small sample size, and none of them was a randomized controlled trial. Two studies focused on only pediatric participants. There was no uniformity in the judgment of the use of pre-operative antibiotics. Due to this variableness among studies, the overall impact of fibrin glue on the rate of infection is inconclusive. This finding is consistent with the previous systematic review conducted by Lund et al. . Recurrence of Pilonidal SinusReturn of the disease is one of the most critical outcomes of interest for both clinicians and patients. The condition is esteemed to have a recurrence if the clinical features reappear and at least one firm or two soft-recurrence criteria are met after the wound has fully healed without any injury to the natal cleft postoperatively . VariousEvery surgical treatment for the pilonidal disease has its recurrence rate, which varies depending on the type of surgical technique and the duration of the follow-up. For example, a low recurrence rate of 0.6% was reported in Limberg & Dufourmentel operations whereas 0.2% in Karydakis & Bascom procedures at 12-month follow-up period. However, primary midline closure was associated with a recurrence rate up to 67.9% 20 years after surgery . FurtherIsik et al., one of these retrospective studies, assessed patients who had a new presentation of a single sinus without previous infection or treatment. They looked into 40 cases. Fibrin glue was used to obliterate the dead space left after the sinus tract was curetted. It reported a recurrence rate of 10% . Sian etThe different range of follow-up and the nature of the pilonidal sinus in participants could be the possible causes of this variability among the studies. The follow-up ranged from four months to 32 months. Generally, the recurrence after fibrin glue therapy does not indicate concern according to the results of included studies. Return to Normal ActivitiesSince the pilonidal disease manifests mainly in the productive age group, the time taken to restart work and school is a significant concern from the socio-economic point of view. Therefore, this factor becomes one of the outcomes of interest. Hardy et al. found that the median time for daily tasks was only three days . Elsey ePatient SatisfactionElsey et al. was the only study that discussed patients' satisfaction rate after having the fibrin glue procedure. This cross-sectional study evaluated the responses of 57 patients who had undergone cleaning of the sinus tract with a surgical scoop followed by fibrin glue injection. Cases were carefully selected, excluding those with acute abscesses and multiple recurrences. 79% of patients were pleased with the outcome due to rapid recovery, less surgical stress, and less pain after receiving this management . The abiWhy Our Study I/s ImportantVarious therapeutic techniques with multiple studies are available to treat the pilonidal disease, which means the ideal one is not recognized yet. According to previously published review articles, the quality of evidence is not strong enough to confirm the impact of fibrin glue on managing pilonidal disease , 23. HowLimitations of Our StudyOur systematic review analyzed six publications, including the recent studies. However, some limitations exist, such as excluding unpublished studies and having no randomized controlled trial to review. Moreover, we had only studies between 2011 and 2021 to focus on the updated information. As a result, the review might not be comprehensive.Our review is to evaluate the therapeutic effect of fibrin glue on pilonidal disease. Although our studies report relatively better outcomes regarding the recurrence rate, infection, and the time to return to normal activities, more extensive studies with proper randomization and longer duration of follow-up are still essential to confirm this weak promising result of fibrin glue. Moreover, none of these studies discussed its cost related to its primary and recurrent therapy. Therefore, the success rate compared to its price is debatable. Since other cost-effective procedures with comparable results are available, future studies should look into them meticulously. It will help discover the most feasible and ideal therapeutic option for pilonidal disease. Further research should also provide more robust evidence for using fibrin glue to fill the sinus tract under local anesthesia in the ambulatory service or general practice among selected patients.


Frostbite (FB) is a severe form of cold injury that may result in significant morbidity. Freezing causes formation of ice crystals and protein denaturation leading to cellular damage and tissue necrosis. Although commonly affecting populations who live and work or become stranded in cold environments, the true prevalence is unknown due to lack of standardized reporting. Dry ice is a solid form of carbon dioxide commonly found in the food industry, that can reach temperatures as cold as -110 degrees Fahrenheit and can be purchased at local department stores. Exposure to dry ice is an unusual cause of FB injury that could occur anywhere, especially in warmer climates. Healthcare professionals practicing in warmer climates may be unprepared to assess and treat patients with such injuries.We describe a case of self-inflicted FB injury to the bilateral lower extremities (BLE) following intentional submersion in dry ice who presented to a Southern U.S. Burn Unit.A 20-year-old man with self-diagnosed Body Integrity Identity Disorder (BIID) sustained a 12% TBSA FB injury to his BLE following intentional submersion in dry ice for an estimated 4 hours . He presented to the Burn Center from an outside facility approximately 12 hours post injury with initial rewarming having already occurred. He immediately underwent catheter directed intra-arterial thrombolysis with tissue plasminogen activator (TPA) for leg length preservation. TPA infusion was initiated at 16 hours post-injury for a total infusion time of 24 hours. Wound care consisted of gentle twice daily cleansing with silver sulfadiazine and mafenide acetate creams. The patient ultimately required bilateral below the knee amputations which successfully healed with minimal autografting to the distal limbs. He was formally diagnosed with schizophrenia by our behavioral health team and initiated on risperidone. He underwent aggressive physical therapy and was discharged home with his parents after 21 days. He underwent weekly mental health follow up appointments and has been seen regularly in our burn and rehabilitation clinic.This unusual case is one of few to describe Grade 4 FB after exposure to dry ice and highlights that severe FB may occur in any climate and can cause severe morbidity. Severe cold injury management is important for burn care professionals to maximize tissue and limb preservation.


We report a case of a 64-year-old man with a fusiform right extracranialvertebral artery aneurysm, spanning over half the extra-cranial V2 segment, presenting with recurrent multi-focal posterior circulation embolicischaemic stroke. The patient was treated with endovascular embolisation of theright vertebral artery to prevent further thrombo-embolic events. Distal andproximal occlusion of the aneurysmal vertebral artery was performed with amicro-vascular plug with partial aneurysm sack embolisation to aid thrombosisand reduce the risk of recanalisation. Two months post procedure MR angiographyconfirmed successful aneurysm occlusion with no post-procedural complication.The patient returned to his normal independent life. Endovascular treatment withvessel sacrifice is an effective treatment with low morbidity and we believe theMVP device to be a efficacious option in the vertebral artery. Primary (non acute traumatic) aneurysms are even rarer and arise due toconnective tissue diseases; predominantly Ehlers-Danlos syndrome, Marfan syndromeand Neurofibromatosis, and much less commonly secondary to arteriosclerosis.Extracranial vertebral artery aneurysms are uncommon and the vast majority of reportsare associated with trauma representing pseudo-aneurysm formation and acute.Reported causes have included such obscure cases as being gored by an ox,68 mass effect causing dysphagia, neck pain1015 and radiculopathy.,, Presentation also includes posterior circulation ischemia and infarction withclinical features of dizziness, diplopia, nausea, dysarthria, dysphagia, ataxia,unilateral limb weakness and visual field defects. In general posterior circulationstrokes account for 20–25% of all ischaemic stroke.Extracranial vertebral artery aneurysms can present following rupture and symptomsrelated to acute haemorrhage,We report an unusual case of a growing chronic long length fusiform vertebral arteryaneurysm extending over half the length of the extra-cranial segment presenting withrecurrent multi-focal embolic posterior circulation acute infarction which wassubsequently treated with endovascular embolisation. In addition we have reviewedthe literature on treatment of chronic and perceived primary extracranial vertebralartery aneurysms and excluded acute trauma cases.A 64-year-old man presented with acute onset of dizziness and a left sided fielddefect. The patient complained of ‘dazzling bright lights’ in the left lower fieldof vision. He had no headache or neck pain and there was no recent trauma. Pastmedical history included cholecystectomy and migraine with aura, but no regularmedications. Subsequently in the patient’s admission further questioning by theinterventional neuroradiologist revealed the patient had fallen down subway stairstwenty years previously with significant trauma but did not receive any treatment.On examination there was a left lower homonymous quadrantinopia. National Instituteof Health Stroke Scale of 1 was attributed to the partial visual field defect.Routine biochemical and hematological investigations were all within normal limitsexcept a mildly elevated cholesterol at 5.1 mmol/L and non-HDL 3.5 mmol/L. ECGdemonstrated sinus rhythm. Blood pressure recorded 181/92 mmHg with the remainingobservations within normal parameters. The patient was a semi-retired publican, anon-smoker and consumed 20units of alcohol per week. Previous soft tissue neckimaging from 2015 for an intramuscular lipoma identified a right vertebral arteryaneurysm with cervical spine remodeling, the patient was asymptomatic and no followup imaging was arranged. Although dedicated vascular imaging was not undertaken atthat time maximal axial aneurysm dimension measured approximately 13 mmmaximally.Initial CT identified hypoattenuation in the right occipital lobe consistent withinfarction subsequently confirmed on MR but with multiple further foci of infarctionin the posterior circulation involving the right occipital lobe, left thalamus andcerebellum in keeping with acute embolic infarction . The T2 CT angiography demonstrated a grossly dilated right vertebral artery measuring up to35 mm in diameter isolated to the V2 . Areas of stenosis wererelated to the constraint of the aneurysmal vertebral artery in the transverseforamina, which would predispose to turbulent flow and hence aneurysm progressionand thrombus formation. The aneurysm had a thick thrombus lining the lumen withareas of fissuring and crenulation , the aneThis case was urgently discussed in a dedicated neurovascular multi-disciplinary teammeeting, composing of interventional neuro-radiologists, neuro-surgeons andneurologists. Careful discussion was undertaken with the patient regarding the riskbenefit of best medical therapy, endovascular or open surgical treatment. Given theevidence of historic ‘silent’ thrombo-embolic events, based on establishednon-restricting multifocal elevated T2 foci on MRI, and the theoretical risk offuture catastrophic major vessel thromboembolism in the posterior circulation thepatients preference was for interventional treatment. Urgent endovascular evaluationand treatment of the aneurysmal right vertebral artery to prevent further embolicischaemic strokes or rupture of the aneurysm was undertaken. Digital subtractionangiography (DSA) confirmed a chronic fusiform aneurysmal right vertebral arterywith areas of saccular dilatation. The origin, V1 segment , V3segment  and V4 segment  and basilarartery were normal .The patient underwent general anaesthesia prior to endovascular intervention(American Society of Anaesthesiologists (ASA) grade 1). Procedure was performed in abiplane neuro-interventional suite .Under ultrasound guidance the right common femoral artery was punctured and a 6 Frsheath inserted. 5000units of intra-arterial heparin was administered. Initialangiogram in the left vertebral artery confirmed excellent calibre and supply to thebasilar and posterior circulation. An unfolded aortic arch was encountered butcatheterisation with a 5 Fr vertebral curve catheter of the right subclavian arterywas relatively uncomplicated. An exchange manoeuvre was performed to gain stableaccess with a 80 cm 8 Fr Neuronmax  long sheath. A 5 FrSofia  with an Excelsior XT-27 microcatheter  and Synchro microwire  was navigated through to the V3segment. Embolisation was performed with a proximal 5 mm micro-vascular plugs (MVP-3Microvascular Plug) and distal 3 mm plug and five platinumcoils (Microplex)  . Post-em atorvastatin 40 mg and amlodipine 5 mg once daily. Two months post proceduretime of flight MR angiography confirmed no flow in the aneurysmal segment andstandard imaging did not demonstrate any post-procedural infarction. The patientreturned to his normal pre-procedural state leading an independent life with no newneurological deficit.The patient was transferred to the neuro-intensive care unit and recovery wasunremarkable, subsequently he was discharged on dual anti-platelet therapy (aspirinand clopidogrel) for 21 days, then clopidogrel 75 mg once daily lifelong, as percurrent secondary prevention guidelines,,,915,,2029 twelve of which were notassociated with a connective tissue disorder  which may have mandated either surgery or complex stent assisted treatment topreserve the vessel.Although direct comparison between surgery and endovascular treatment of extracranialvertebral artery aneurysm has not been performed or likely to be feasible, given thelow incidence, treatment of intracranial vertebral artery dissection aneurysms hasbeen subject to meta-analysis from which one might glean some information. Bothsurgical trapping and stent-assisted coiling demonstrated high rates of goodlong-term neurologic outcomes and low recurrence and mortality rates in intracranialdissecting vertebral artery aneurysms, but one should consider these in the contextof acute dissection and the pre-existing morbid state.In the literature there were twenty-one patients with follow up which reportedperi-operative complications in four patients and symptomatic improvement wasreported in fourteen patients (66%), one patient had recurrent radiculopathy, onehad new radiculopathy and one endovascular patient developed a delayedarterio-venous fistula. Therefore treatment of vertebral artery aneurysms can bedeemed relatively safe and lead to improvement in local symptoms. The risk profileis similar to any endovascular vessel occlusion procedure. Technical factors would also preclude the use of flow diverting stent as thelargest available measure 5 mm in maximal diameter, although the stent could besized to the ‘normal’ proximal and distal vessel there would still be long length ofstent with no apposition. The authors felt immediate vessel sacrifice with themicrovascular plug device was the quickest option with the lowest risk profile. Itwas felt preservation of the distal extracranial vertebral artery (V3 segment) wasnot required as the main aim was to preserve the right PICA, which was clearlyachieved by retrograde flow in the right V4 segment. Vessel sacrifice has long beenknown to be a definitive procedure to manage any aneurysm with low morbidity ifadequate intracranial anastomosis and perfusion is confirmed. The microvascular plug(MVP) device has been primarily used in peripheral vascular procedures, such as inrenal artery occlusion. The benefit of the MVP was ease of deployment and relative low cost comparedto specific neurovascular devices, perhaps historical detachable balloon devicewould also have been a consideration, but have since been removed from the market. Complete aneurysm sacembolization was not undertaken as this was felt to be excessive as proximal anddistal control was achieved and also this would allow some regression in the localmass effect given the distortion of the pharynx, in addition this would haverequired many coils with significant cost. Of note previous report of proximalligation resulted in continued aneurysm filling from muscular anastomosis and a case treated with proximal endovascular embolisation resulted inpersistent filling and even developed aberrant outflow to become fistulous. Therefore it is essential to obtain distal and proximal occlusion. In thiscase partial embolisation of the aneurysm sack was also performed to aid thrombosisand reduce the risk of recanalisation.Flow diverting stent placement was not favored in this case for several reasons.Primarily wall apposition plays an important role in speed of and likelihood ofendothelialization of the flow diverting stent, this in turn is critically importantfor aneurysm occlusion., however death from rupture into the thoracic cavity despite emergentendovascular balloon placement to control haemorrhage has been reported. The risk of lifetime rupture is unknown given the rarity of these lesions andthe incidence is likely higher than reported as many cases remain asymptomatic. Mostreports are associated with an underlying connective tissue disorder and growth ofthe aneurysm can be asymptomatic, aneurysms have been reported to measure up to 5 cmdiameter, over ten times the normal calibre. Continued aneurysm growth must be taken into consideration, in a paediatricpatient with Neurofibromatosis type-1 followed up from age one to seven showedprogressive enlargement of a vertebral aneurysm with associated upper limb symptoms,as well as massive aneurysmal dilatation of the thoracic aorta. This highlights the importance of appropriately counselling the patient ontreatment and possible future growth if untreated.Rupture of an extracranial vertebral artery aneurysm can result in simple haematomaand neck painExtracranial vertebral artery aneurysms are a rare entity and can present withposterior circulation ischaemic strokes. They are most often associated with anunderlying connective tissue disorder; however, primary aneurysm formation orprevious trauma are possibilities to consider. Endovascular treatment with vesselsacrifice is an effective treatment with low morbidity and we believe the MVP deviceto be a efficacious option in the vertebral artery.


In conclusion, neurological recovery was an independent factor having a significant positive association with post-operative neck pain attenuation in patients with cervical myelopathy caused by OPLL who underwent cervical spine surgery.Although favourable surgical outcomes for myelopathy caused by cervical ossification of the posterior longitudinal ligament (OPLL) have been reported, factors significantly associated with post-operative neck pain attenuation still remain unclear. The primary aim of the present study was to determine factors significantly associated with post-operative neck pain attenuation in patients with cervical OPLL using a prospective multi-centre registry of surgically treated cervical OPLL. Significant postoperative neck pain reduction (50% reduction of neck pain) was achieved in 31.3% of patients. There was no significant difference in neck pain attenuation between surgical procedures. Statistical analyses with univariate analyses followed by stepwise logistic regression revealed neurological recovery as a factor having a significant positive association with post-operative neck pain attenuation ( Computed tomography screening has revealed an unexpectedly high prevalence of OPLL in the cervical spine, which affects about 7–10% of the general population in Japan3. Increase of thickness of ossification foci can cause compression of nerve roots and the spinal cord, possibly resulting in neurological deficits4. Favourable surgical outcomes for cervical OPLL have been reported. Nerve root and spinal cord symptoms including numbness, palsy, and vesico-rectal disturbance can be attenuated after surgery for cervical OPLL5.Ossification of the posterior longitudinal ligament (OPLL) is a disease with heterotopic ossification in the spinal posterior longitudinal ligament6. Previous reports revealed neck pain attenuation by cervical spine decompression/fusion surgeries for cervical OPLL10. However, the precise aetiology of neck pain, postoperative change of neck pain, and factors significantly associated with post-operative neck pain attenuation in patients with cervical OPLL still remain unclear.In addition to neurological symptoms including radiculopathy and myelopathy, cervical OPLL can cause local symptoms such as neck pain and stiffness, which can be main complaints for patientsThe primary aim of the present study was to elucidate the post-operative change of neck pain and to determine factors significantly associated with post-operative neck pain attenuation in patients with cervical OPLL using a prospective multi-centre registry of surgically treated cervical OPLL.Patient demographics are shown in Table There was no significant difference in pre-operative VAS neck pain score between surgical procedures. Post-operative VAS neck pain scores, neck pain reduction score, and proportion of neck pain reduction showed no significant difference between surgical procedures Table .Table 3Cp = 0.04, odds ratio 5.68 , Table Age, diabetes mellitus, disease duration and Japanese Orthopedic Association score for evaluating cervical myelopathy (JOA score) recovery rate were identified as possible candidates for factors having significant association with postoperative neck pain attenuation by initial uni-variate analyses Table . LogistiThe present results demonstrated that neurological recovery was an independent factor having a significant positive association with post-operative neck pain attenuation.There are many previous reports showing the possible aetiologies of neck pain.11. Various kinds of muscle preserving posterior approaches have been reported to attenuate post-operative axial neck pain14. The anterior approach does not invade the posterior musculo-ligamentous complex; therefore, post-operative muscle-related neck pain can be decreased compared with that in the posterior approach15. However, the present results showed that there is no significant difference in post-operative neck pain attenuation between surgical approaches (anterior and posterior) or surgical procedures , suggesting that surgical damage of the cervical musculature has no significant association with post-operative neck pain in the present patient series. Possible explanations for this discrepancy in muscle damage-related neck pain between previous reports and the present data might be as follows: the posterior approach-related muscle damage decreased according to the recent popularization of muscle-preserving posterior approaches and the impact of posterior approach-related muscle damage might be limited to the early post-operative phase and not the chronic phase.Axial pain, as first reported by Hosono, which is defined as post-operative neck pain related to posterior approach-induced muscle damage, is regarded as a major cause of post-operative neck pain18. Fusion surgery can be indicated for discogenic/facet genic neck pain because this category of pain can theoretically be attenuated by fusion of the pain-generating segment19. However, the present results unexpectedly showed that there was no significant difference in post-operative neck pain attenuation between segmental motion-preserving laminoplasty and fusion surgeries (anterior and posterior). Therefore, discogenic/facet genic neck pain was not likely to be a major aetiology of neck pain in the present series.Discogenic and/or facet genic neck pain, which is caused by degenerated intervertebral disks and facet joints accompanied with segmental instability, can be another possible source of neck pain19. Segmental spinal cord sign caused by compressive myelopathy may, like girdle pain, be another origin of neck pain20. Segmental spinal cord compression can cause local impairment of the spinothalamic tract at its chiasma at the central grey matter of the spinal cord21. Irrespective of the precise cause, a large-scale cohort study revealed that cervical myelopathy can cause neck pain22.The present results revealed post-operative neurological recovery as an independent factor having a significant association with post-operative neck pain attenuation. These lines of evidence suggest that neurogenic pain is one of the major causes of neck pain in patients with cervical OPLL. There might be several possible origins of myelopathy-related neck pain. Spinal cord compression can stimulate the posterior ramus of the spinal nerve, possibly resulting in neck painIn addition, there is a possibility that the natural course of the disease is attributed to postoperative neck pain attenuation. Theoretically, progression of ossification foci can lead to spontaneous fusion of intervertebral segments, potentially resulting in neck pain attenuation. However, we could not find articles describing the natural history of neck pain in OPLL patients. Therefore, we had no proper answer for this question at present. Our multicenter study group is now constructing another prospective registry for OPLL patients receiving non-operative treatment with long term follow-up. Precise natural course of OPLL might be elucidated in future.23. Therefore, the outcome might be changed significantly if cervical sagittal alignment data were added. To solve this problem, future collection of data regarding cervical sagittal alignment is needed. Another major limitation of the present study is that the present registry lacks information about the precise location and characteristics of neck pain and evaluation of neuropathic pain. Those data are important to elucidate the origin of neck pain. As a result, we can only speculate on the origin of neck pain using indirect evidence including post-operative change of neck pain, pre-operative patient factors, surgical factors, radiological changes, and neurological status. Future data collection of the precise characteristics of neck pain and neuropathic pain evaluation are warranted.The present study includes several major limitations. The present registry lacks data regarding cervical sagittal alignment. Recently, the concept of sagittal alignment has been introduced to the cervical spine, similar to the thoracolumbar spine. Cervical sagittal alignment is important to evaluate neck pain because it has been reported to correlate with neck painIn conclusion, neurological recovery was an independent factor having a significant positive association with post-operative neck pain attenuation in a prospective study of a cohort of patients with cervical myelopathy caused by OPLL who underwent cervical spine surgery.We used a prospective cohort design for the present study.We assembled as investigator’s meeting before the initiation of the present study and twice a year during the study period for training to standardize the data collection and imaging analyses. All the clinical and imaging data were collected by physicians except for surgeons who performed surgery in each institute. Cleaning of collected data was performed by the committee member of the present study group. Missing data was mainly caused by patients’ drop out from follow-up.24. We also excluded patients received anterior–posterior combined surgery because the number of those patients was very small (n = 7) to obtain statistical significance.The registry included data from 478 patients who underwent cervical spine surgery for myelopathy caused by cervical OPLL. Amongst these patients, we excluded data from those who lacked pre-operative neck pain evaluation (40 cases), who showed a pre-operative neck pain score < 30 mm on a visual analogue scale  to avoid possible ceiling effects in evaluation for pain attenuation and several previous pain trials set similar exclusion criteriaTherefore, we included data from 265 patients with cervical OPLL and a pre-operative neck pain severity score ≥ 30 mm on a VAS. Patient demographics are shown in Table 24. In addition, another reason why we adopted 50% pain reduction as the outcome measure is that the impact of absolute value of pain evaluation could differ between patients having different preoperative neck pain.Neck pain was evaluated using the VAS score pre- and post-operatively. The proportion of VAS score reduction was calculated as (pre-operative VAS neck pain—post-operative VAS neck pain) / pre-operative VAS neck pain × 100 (%). Post-operative neck pain deterioration was expressed as the negative proportion of VAS score reduction. We employed “50% pain reduction” as classification for sufficient postoperative neck pain attenuation because we think it is comprehensive at a glance and it is one of the popular outcomes in pain research fieldPossible explanatory factors having significant association with postoperative neck pain attenuation were as followings.Patient factors Patients factors included age at surgery, sex, body mass index, disease duration, and diabetes mellitus.Neurological status Pre- and post-operative neurological status were analysed using the Japanese Orthopedic Association score for evaluating cervical myelopathy . The recovery rate of JOA score was calculated using the following method: (post-operative JOA score—pre-operative JOA score) / (17 (full mark)—pre-operative JOA score) × 100 (%)26. Post-operative neurological deterioration was expressed as the negative value JOA score recovery rate.Imaging factors Imaging factors including types of OPLL  in lateral radiogram of cervical spine  curves to determine their cut-off values. All the statistical analyses were conducted with statistical analytics software JMP  under the supervision by the biostatistician in our department (one of the co-author KF). Those statistical analyses were performed on data obtained 1 and 2 years after surgery.Factors showing a


Immigrant family caregivers for persons living with dementia (PWD) have constant stress due to the 24/7 responsibility. These family caregivers of PWD often have high morbidity and mortality. We provided a cultural and language specific home-visit intervention for these vulnerable family caregivers. There is a lack of an objective measure of stress for caregivers. We assessed caregivers’ stress by measuring heart rate variability (HRV), a physiological measure of stress, using a smartwatch for a one-month intervention. Weekly home visits for a month were provided to dementia family caregivers by trained community health workers with stress reduction techniques: mindful breathing and compassionate listening. Linear mixed-effect models were used to analyze the trends for the daily stress levels as measured by HRV from the smartwatch. We had 22 participants who completed the 4-week intervention . The models showed a significant decrease in the stress level of all participants for 3 weeks . At 28 days (4 weeks) all three groups showed a decrease in stress: Korean group , Vietnamese group , Latino group  and all caregivers . The findings demonstrated a reduction of immigrant family caregiver stress with a home-visit weekly intervention for one month using mindful breathing and compassionate listening by culturally/linguistically appropriate community health workers. Large-scale studies to determine long-term outcomes of family dementia caregivers are necessary and should be carried out.


Parachute mitral valve with reticular chordae tendineae is an extremely rare anomaly.We present a case of parachute mitral valve associated with distinctive reticular chordae tendineae in an adult. It was diagnosed from the echocardiogram. The patient was referred for surgery. Valve analysis showed thickened mitral valve leaflets and commissures. The chordae tendinae were lengthy and thick. All the chordae tendinae merged into a solitary papillary muscle. A distinctive reticular fibrous tissue was found on mitral valve apparatus as the chordae tendinae intermixed each other. The only functional communication between the left atrium and the left ventricle was through the reticular spaces. This anomaly was considered to be unrepairable and was replaced with a mechanical valve.An extremely rare and unique case of parachute mitral valve associated with reticular chordae tendineae was reported. Mitral valve replacement is a reasonable choice in patients with parachute mitral valve with reticular chordae tendineae.The online version contains supplementary material available at 10.1186/s13019-021-01448-4. Parachute mitral valve (PMV) is characterized by a unifocal attachment of the mitral chordae tendinae to a single papillary muscle , 2. VeryA 36-year old man developed exertional dyspnea and fatigue of 2 months duration. There was no history of orthopnea or paroxysmal nocturnal dyspnea. Physical examination revealed a well-built man with supine right upper arm blood pressure of 135/76 mmHg, regular pulse rate of 88 beats/min, and no evidence of heart failure. Precordial examination showed normal heart sounds, a 3/6 diastolic rumble murmur. No opening snap or third sound was audible. An electrocardiogram revealed sinus rhythm with a heart rate of 86beats/min, left atrial overload and normal atrio-ventricular conduction. The chest skiagram showed mild left atrial prominence. Routine Laboratory tests showed no anaemia, liver dysfunction or renal dysfunction. He underwent detailed transthoracic echocardiographic examination.2 with a trans-mitral peak and mean gradient of 9 and 5 mmHg respectively. Abnormal chordae tendineae with reticular structures attached to a solitary papillary muscle originating from the posteromedial wall was detected (Fig. Echocardiogram revealed dilated left atrium, normal left ventricle and normal left ventricular function. Mitral valve area by planimetry and the pressure half-time method was 1.02 cmThe patient was referred for surgery. The operation was performed through a minimally invasive right thoracotomy with the use of cardiopulmonary bypass. Through an interatrial approach, the mitral annulus, leaflets, chordae tendinae, and papillary muscles were exposed. Valve analysis showed two thickened mitral valve leaflets and commissures, but all the chordae tendinae merged into a solitary papillary muscle. It presented as a funnel-type structure. The chordae tendinae were lengthy and thick. A distinctive reticular fibrous diaphragm with scattered holes obstructing the valvular orifice was found on mitral valve apparatus as the chordae tendinae intermixed each other Fig. . An addiThe postoperative recovery was uneventful. The patient was discharged 7 days after surgery. At the 5-year follow-up examination, the patient was in good health.Parachute mitral valve is a very rare congenital mitral valve anomaly which may remain asymptomatic in life-time or may present with mitral valve stenosis or regurgitation or both. It is characterized by unifocal attachment of the chordae tendineae of both leaflets to a single papillary muscle. It is highly associated with other congenital heart anomalies. Isolated PMV in an adult is very rare, while the presence of a reticular chordae tendineae--as in the present case--is extremely exceptional.In the developmental process of mitral valve, PMV occurs due to disturbed delamination of the anterior and posterior parts of the trabecular ridge . These pAlthough adult patients with isolated PMV usually present with dyspnea, PMV may be incidentally diagnosed during echocardiography. Such patients generally require no medical or surgical treatment. Mitral valve surgery when feasible needs to be performed only in those patients with hemodynamically significant stenosis or regurgitation . It is wWe reported an extremely rare and unique case of parachute mitral valve associated with reticular chordae tendineae in an adult. Mitral valve replacement is a reasonable choice in patients with this anomaly when the leaflets are thickened and severely stenotic.Additional file 1:. Abnormal chordae tendineae which was attached to a solitary papillary muscle originating from the posteromedial wall was detected. A small muscular ridge or trabecula was present at the location of anterolateral papillary muscle without any chordal attachment.Additional file 2:. 3D transesophageal echocardiography showed reticular chordae tendineae with scattered holes among them.Additional file 3:. Valve analysis showed all the chordae tendinae merged into only 1 major papillary muscle. The chordae tendinae were lengthy and thick. A distinctive reticular fibrous diaphragm with scattered holes obstructing the valvular orifice was found on mitral valve apparatus as the chordae tendinae intermixed each other. The only functional communication between the left atrium and the left ventricular was through the reticular spaces.


To describe the spontaneous closure of a degenerative lamellar macular hole with epiretinal proliferation (LHEP) as documented with tracked spectral domain optical coherence tomography (SD-OCT).A 54-years-old diabetic female patient presented with progressive vision loss in the left eye. SD-OCT illustrated LHEP associated with cystic fluid in the outer nuclear layer. Sequentially tracked SD-OCT showed progressive closure of the degenerative lamellar macular hole and resolution of the CME over almost 4 years, in the absence of any surgical intervention.LHEP may represent a specialized form of degenerative epiretinal membrane associated with Muller cell activation. Spontaneous degenerative LMH closure may rarely occur with these lesion types, in the absence of surgical intervention, possibly due to Muller cell proliferation preceded by PVD. Lamellar macular hole (LMH) with epiretinal proliferation or LHEP is a unique form of degeneration associated with secondary Muller Cell proliferation . These EIn this report, an interesting case of LHEP is presented in which the lamellar macular hole spontaneously closed without surgical intervention. We present the sequential tracked OCT findings of this outcome and discuss the mechanism of closure which may relate to Muller cell activation preceded by posterior vitreous detachment (PVD).A 54-year-old female type 2 diabetic patient presented with a history of progressive vision loss of the left eye (OS). The right eye was legally blind due to end stage proliferative diabetic retinopathy (PDR).On examination, best corrected visual acuity (VA) was hand motions in the right eye and 20/200 in the left eye. Ophthalmoscopic retinal examination OD was not possible due to a prepupillary fibrotic membrane. Retinal examination OS showed panretinal photocoagulation scars and evidence of regressed fibrotic PDR.Spectral domain – optical coherence tomography (SD-OCT) OS illustrated a lamellar macular hole with epiretinal proliferation associated with cystic degeneration predominantly located in the outer nuclear layer Fig. A. A gradSD-OCT 1 year later illustrated persistent LHEP, improvement of the CME and a partial grade 3 PVD  or lamellar macular holes (LMH) with epiretinal proliferation (LHEP) represent a distinct subset of ERM easily differentiated from tractional ERMs . AlthougMuller cell activation and proliferation may lead to non-surgical closure of the LMH that was documented in this case report with sequentially tracked SD-OCT over 2 years . BringmaSurgical management may be deferred in these cases due to the degenerative Muller cell component and the stable natural history.LHEP may represent a specialized form of degenerative lamellar macular hole associated with Muller cell proliferation. Non surgical closure may rarely occur with these lesion types possibly due to Muller cell activation preceded by PVD.


In vivo modeling combined with CRISPR/Cas9-mediated somatic genome editing has contributed to elucidating the functional importance of specific genetic alterations in human tumors. Our recent work uncovered tumor suppressor pathways that affect EGFR-driven lung tumor growth and sensitivity to tyrosine kinase inhibitors and reflect the mutational landscape and treatment outcomes in the human disease. Sequencing data of human tumors show that EGFR alterations co-occur with alterations in many putative tumor suppressor genes.2 Whether these alterations have biological implications and whether their relative alteration frequency reflects their functional importance remains largely unknown. Understanding the extent to which tumor suppressor gene alterations contribute to TKI sensitivity and resistance could improve treatment approaches (EGFR mutant tumors.2Tyrosine kinase inhibitors (TKIs) are the standard of care treatment for oncogenic epidermal growth factor receptor (EGFR)-driven lung adenocarcinomas.proaches . Moreovein vivo studies on the function of tumor suppressor genes in oncogenic EGFR-driven lung cancer. This was at least partially due to the absence of suitable autochthonous EGFR-driven lung cancer models with which to investigate the biological consequences of gene inactivation.3 In our recent work, we leveraged tumor barcoding with high-throughput barcode sequencing (Tuba-seq)5 and applied it to a novel model of EGFR mutant and Transformation related protein 53 -deficient lung adenocarcinoma to study the functional importance of tumor suppressor genes that are frequently altered in human lung tumors.3 –6 Our findings revealed tumor suppressor genes that when inactivated promoted tumor growth, most notably RNA binding motif protein 10 (Rbm10), Retinoblastoma 1 (Rb1), and Adenomatous polyposis coli (Apc).3 Importantly, these tumor suppressor genes were also some of the most frequently altered genes in EGFR/P53 mutant human lung tumors, supporting the importance of these tumor suppressor pathways in driving EGFR mutant lung tumors.3AT-rich interaction domain 1A (Arid1a) and Cyclin-dependent kinase inhibitor 2A (Cdkn2a) inactivation appeared to increase tumor growth only later during tumor progression, suggesting that specific tumor suppressor genes can have different effects at different stages of tumor development. Inactivation of other putative tumor suppressor genes that we investigated did not promote tumor growth, indicating that the function of some tumor suppressor genes may be highly context-dependent  may play a role in determining genetic epistasis, suggesting that experimental approaches are particularly important for understanding why this is observed.7 Oncogenic EGFR alterations (mainly affecting EGFR exons 18 through 21) and oncogenic Kirsten rat sarcoma viral oncogene homologue (KRAS) missense mutations  represent major drivers of lung adenocarcinoma.2 Given that both these oncogenes are components of the same pathway, we anticipated that tumor suppressor genes would have similar impacts on in vivo growth of EGFR and KRAS mutant lung tumors. Although inactivation of Rbm10, Rb1, or Apc did have similar effects on EGFR and KRAS mutant tumor growth, Serine/threonine kinase 11  and SET domain containing 2, histone lysine methyltransferase (Setd2) inactivation had opposite effects in the two oncogenic settings. Lkb1 and Setd2 inactivation are two of the strongest drivers of KRAS mutant tumor growth; however, their inactivation reduced EGFR mutant tumor growth.8 These results correlate with the relative frequency of LKB1 and SETD2 alterations in human EGFR and KRAS mutant lung tumors, suggesting the existence of a synthetic lethal relationship between Lkb1/Setd2 inactivation and oncogenic EGFR. These findings underscore the importance of quantitative modeling of genetic alterations in vivo. More broadly, the observation that inactivation of certain genes can have different effects depending on the specific oncogenic alteration present  revealed surprising context specificity of the role of these genes in cancer  inactivation reduced sensitivity to this therapy.3 Our in vivo data mirror clinical data suggesting that KEAP1 pathway alterations predict poor clinical responses to TKIs.3 Thus, we established a causal link between this tumor suppressor pathway and TKI sensitivity in EGFR mutant lung adenocarcinoma.Osimertinib, a third generation TKI that leads to better overall survival compared to other TKIs, has been approved as first-line therapy for patients with metastatic EGFR-driven lung cancer.in vivo CRISPR/Cas9 screening approach that we used allows us to interrogate multiple genes simultaneously and assess their contributions to tumor phenotypes.11 Thus, it provides quantitative cause-and-effect information and avoids confounding factors that are inevitable in human tumors . However, our model systems do not yet recreate the extent of genomic complexity and intratumoral heterogeneity found in human lung tumors. Future studies will also be required to uncover the molecular mechanisms by which these tumor suppressors normally constrain tumor growth and by which their inactivation sensitizes tumors to therapy. Our study represents an initial step in defining the role of tumor suppressor genes in oncogenic EGFR-driven lung tumors. We anticipate that assessing broader panels of putative tumor suppressors will further elucidate the functional genomic landscape of this disease and allow genotypes to be related to diverse cancer phenotypes, including their response to different therapies. Despite the efficacy of single agent osimertinib, quantifying the impact of rational combination therapies on defined genotypes of lung tumors will drive further gains in the treatment of specific subsets of tumors. We envision that these types of multiplexed in vivo studies will ultimately contribute to the development of tailored treatments for patients with EGFR mutant lung cancer.The multiplexed


These friendship features (W1) were investigated as potential mediators of the prospective association between teacher-rated ADHD symptoms (W1) and self-rated depressive symptoms (W2) seven months later. Parent–child relationship quality (W1) was tested as a moderator of any indirect effects of ADHD on depression via friendship. ADHD symptoms were inversely associated with friendship presence, friendship quality and positive characteristics of classroom friendship groups. Depressive symptoms were inversely associated with presence and quality of friendships. Friendship quality had indirect effects in the association between ADHD and subsequent depressive symptoms. There was some evidence of moderated mediation, whereby indirect effects via friendship quality attenuated slightly as children reported warmer parent–child relationships. This highlights the importance of considering the quality of friendships and parent–child relationships in children with ADHD symptoms. Fostering good quality relationships may help disrupt the link between ADHD symptomology and subsequent depression risk.Attention deficit/hyperactivity disorder (ADHD) is associated with friendship difficulties. This may partly account for the increasingly recognised association between ADHD and subsequent depression. Little is known about the types of friendship difficulties that could contribute to the association between ADHD and depressive symptoms and whether other relationships, such as parent–child relationships, can mitigate against potential adverse effects of friendship difficulties. In a representative UK school sample (The online version contains supplementary material available at 10.1007/s10802-021-00798-w. Attention Deficit/Hyperactivity Disorder (ADHD) is a DSM-5  are important in increasing vulnerability to depressive symptoms in those with elevated ADHD symptoms. A secondary aim of this study was to investigate whether any indirect effects via elements of friendship were moderated by mother–child or father-child relationship quality. A follow-up exploratory research question was whether indirect effects differed according to sex. The study included children in the first year of secondary school followed over a seven-month timespan.n = 1372). For 1020 of these 1372 children (74.3%), teachers completed the section rating the children’s baseline ADHD symptoms. Of the 1020 children, self-rated depressive symptom data at follow-up were available for 901. Of these, there were 752  for whom data were additionally available on friendship and sociodemographic variables. To address bias that might be caused by missingness, predictors of missingness were investigated  in the last month completed a measure assessing their perception of each parent’s warmth and hostility towards them using the Iowa family interaction rating scale . All analyses presented are adjusted for confounders by including these variables in the models as covariates.ADHD symptoms were standardised meaning a point increase in SDQ hyperactivity score was equivalent to a standard deviation unit increase. Linear regression was used to test the association between ADHD symptoms and depressive symptoms 7 months later. Separate linear and logistic regressions were used as appropriate to test associations between ADHD symptoms and indicators of three friendship elements , and to test associations of these friendship indicators (standardised if continuous) with depressive symptoms. Regressions included the school class as a random effect to account for potential hierarchical data structure or clustering.To test whether the different features of friendship contributed to the association of ADHD and depressive symptoms, indirect effects were tested separately using the [sureg] STATA command. Sureg conducts Seemingly Unrelated Regressions Zellner, , from whZ-tests) of the difference between the observed indirect effect at the mean level of the moderator compared to the mean level of the moderator -1SD (for hostility) or +1SD (for warmth) were conducted. To investigate which path(s) in the indirect effects were being moderated, we additionally tested models with an interaction effect on the path between ADHD symptoms and friendship or the path between friendship and depression symptoms only.Moderated mediation was tested using [sureg] to investigate whether any indirect effects via friendship varied according to the warmth or hostility of parent–child relationships. The model used tested combined moderation of the pathway from ADHD symptoms to friendship and the pathway from friendship to depression symptoms  p = 0.002).ADHD symptoms at baseline were associated with naming fewer friends and lower friendship quality at baseline, both of which were associated with increased depressive symptoms at follow-up. ADHD symptoms were also associated with being part of a classroom friendship group that had higher total difficulties and was rated as less cooperative and more disruptive at baseline. Stability of the best friendship from baseline to follow-up was inversely associated with depressive symptoms Table . ADHD syADHD and depressive symptoms were associated directly and indirectly via friendship quality, both for best friend and top three friends, when tested separately Table . They shThe indirect effect of ADHD symptoms on depressive symptoms via friendship quality was larger for females than males (Supplement p = 0.040) as mother–child relationship warmth increased   children reported that they had been in contact with their mother in the last month and 92.5% with their father. Indirect effects via top three friendships quality attenuated  Fig. .Fig. 1PlAll results were very similar before and after imputation Below is the link to the electronic supplementary material.


Glioblastoma (GBM) is the most common primary malignant brain tumor. Sex has been shown to be an important prognostic factor for GBM. The purpose of this study was to develop and independently validate sex-specific nomograms for estimation of individualized GBM survival probabilities using data from 2 independent NRG Oncology clinical trials.This analysis included information on 752 (NRG/RTOG 0525) and 599 (NRG/RTOG 0825) patients with newly diagnosed GBM. The Cox proportional hazard models by sex were developed using NRG/RTOG 0525 and significant variables were identified using a backward selection procedure. The final selected models by sex were then independently validated using NRG/RTOG 0825.Final nomograms were built by sex. Age at diagnosis, KPS, MGMT promoter methylation and location of tumor were common significant predictors of survival for both sexes. For both sexes, tumors in the frontal lobes had significantly better survival than tumors of multiple sites. Extent of resection, and use of corticosteroids were significant predictors of survival for males.https://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/.A sex specific nomogram that assesses individualized survival probabilities  for patients with GBM could be more useful than estimation of overall survival as there are factors that differ between males and females. A user friendly online application can be found here—The online version contains supplementary material available at 10.1007/s11060-021-03886-5. Glioblastoma (GBM) represents 48.3% of all malignant primary brain tumors . Despite) promoter methylation status and presence of an IDH1 or IDH2 mutation are well-validated prognostic factors, [While extent of resection, age at diagnosis, Karnofsky performance status (KPS), O-6-Methylguanine-DNA Methyltransferase  wildtype GBM patients specifically . These nExempt approval was obtained from the University Hospitals Institutional Review Board (IRB) for all analyses presented. De-identified data were provided by NRG Oncology for the clinical trials NRG/RTOG 0525 and NRG/RTOG 0825 for which a written informed consent was obtained for each study subject under IRB approved protocols for each participating NRG study site , 15. NRGDescriptive statistics were used to assess any differences in patient characteristics and prognostic factors by sex using t-tests for continuous variables and chi-square tests for categorical variables. Non-parametric equivalents were used as appropriate. The analyses were performed using NRG/RTOG 0525 as the training dataset and NRG/RTOG 0825 as the validation dataset. Both overall survival (OS) and progression-free survival (PFS) were examined for the trial dataset using the Kaplan–Meier method and were compared by sex using the log-rank test. Upon examination of the Shoenfeld residuals by sex, the proportional hazards assumption for all analyses by sex was not violated.In the initial phase of nomogram development to select prognostic factors, we fit a multivariable Cox proportional hazards model by sex for both OS and PFS to the training set (0525). Cox models were found to be superior for survival prediction on these datasets in a previous publication , and a mhttps://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/. All analysis were performed using R v3.6.0 (http://www.r-project.org/) and the online application was developed using R Shiny application.Calibration of the final models by sex for both OS and PFS for both training and validation dataset was visually evaluated by assigning all patients into quintiles of the nomogram-predicted survival probabilities and plotting the mean nomogram predicted survival probability against the Kaplan–Meier estimated survival for each quintile. A user-friendly online application to obtain individualized predicted survival probabilities by sex was developed and can be found here—In both trials, treatment either did not affect primary outcomes (OS and PFS) or the outcomes did not reach the prespecified improvement target; therefore, the data from both of the studies were used in this analysis . The comparison of patient characteristics between the trials is shown in Supplemental Table Kaplan–Meier curves were generated for OS and PFS for both NRG/RTOG 0525, the training dataset  and validation (NRG/RTOG 0825) datasets for predicted 6-, 12-, and 24-month overall survival by sex . This tool will be useful to health care providers in determining individualized survival probabilities by sex. Further research should be done to better characterize the exact biological mechanisms underlying sex differences in GBM.The differences in the nomograms by sex shown here indicates that the prognosis of females and males may be different and that these nomograms are useful tools for estimating patient-level survival probabilities. To facilitate clinical use of this nomogram, free software for its implementation is provided (Supplementary file1 (DOCX 296 kb)Below is the link to the electronic supplementary material.


OBJECTIVES/GOALS: Clinical translational studies inform clinical practice patterns through dissemination of clinical practice guidelines (CPG). In EM practices change to rapidly for timely local EHR implementation. We test the OMG BPM+Health specification for rapid deployment of best practices relevant to EM. METHODS/STUDY POPULATION: The OMG Business Process Management for Healthcare  specification combines BPMN™ with Case Management Model and Notation (CMMN™) and Decision Model and Notations (DMN™) to “disseminate and leverage evidence-based best-practices at the point of care.” The American College of Emergency Physicians (ACEP) Board-certified Emergency Physicians modeled practice guidelines in the BPM+ modeling language during on-line meetings. Two common emergency conditions were selected for initial pilot testing: 1) evaluation and treatment of first trimester bleeding in pregnant patients, and 2) the evaluation and treatment of non-traumatic low back pain. RESULTS/ANTICIPATED RESULTS: The protocols were successfully modeled during four on-line meetings in less than 2 months. Process steps from initial evaluation to disposition were implemented using BPMN™. When clinicians need to evaluate the patient to collect data for decision making the inputs and outputs were modeled in CMMN™. Decision logic is represented as DMN™. The software tool linked the components for easy browsing and authoring the logic. The Physicians easily followed the displayed logic. The practice recommendations from each policy were successfully modeled, using the standard BPM+ notation to support rapid implementation in EHRs. Detailed implementation specifications will be shared. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot project demonstrated the feasibility of the OMG approach to solving Clinical Practice Guideline Implementation and Dissemination Barriers. Ongoing work by involved specialty societies will be necessary to demonstrate the scalability and sustainability of this approach.


Mitochondrial DNA (mtDNA) may play an important role in Alzheimer’s disease (AD) and cognitive decline. A particular haplogroup of mtDNA (haplogroup J), has been observed more commonly in patients with AD than in cognitively normal controls. We used mtDNA haplogroups to predict change in cognitive performance over seven years. We hypothesized that haplogroup J would predict poorer cognitive function and steeper cognitive decline. We analyzed data from 140 cognitively normal older adults (age 65+) who participated in the University of Kansas Alzheimer’s Disease Center annual registry. We used factor analysis to create three composite scores  from 11 individual cognitive tests. We performed latent growth curve modeling to describe trajectories of cognitive performance and change. We compared haplogroup H, the most common, to haplogroup J, the potential risk group. Results indicated haplogroup J carriers had significantly lower baseline performance  and slower rates of improvement  on tests of verbal memory compared to haplogroup H. For executive function, groups did not differ at baseline , but haplogroup J had slower rates of improvement . There were no differences in attention across groups in performance  or change . Our results reinforce the important role of mtDNA in changes to cognitive function with aging and imply that the effects of haplogroup J may vary across cognitive domains. Future research should investigate the mechanisms by which mtDNA might affect performance on specific cognitive domains across haplogroups.


Subacute cutaneous lupus erythematosus (SCLE) is a rare cutaneous lupus erythematosus (CLE) subtype manifesting in middle-aged Caucasians with photo-distributed papulosquamous or annular lesions. Drug-induced SCLE (DI-SCLE) forms present in a similar manner but direct oral anticoagulants are rarely implicated. We report an unusual case of SCLE in a 37-year-old African American patient with a history of unprovoked deep vein thromboses (DVT) who presented with new-onset photoprotected polymorphic lesions two months after the initiation of apixaban anticoagulation therapy. Our case demonstrates the heterogeneous nature of SCLE presentation and highlights the possibility of apixaban as a potential causative agent of DI-SCLE in immunogenetically susceptible individuals. Moreover, we hypothesize on the etiopathogenesis of our patient’s atypical presentation. Subacute cutaneous lupus erythematosus (SCLE) is a rare cutaneous lupus erythematosus (CLE) subtype, and it usually manifests in middle-aged Caucasian individuals . SCLE prA 37-year-old African American female with a history of two unprovoked deep venous thromboses (DVT) treated with apixaban was evaluated for a pruritic rash of two weeks' duration. She had started apixaban two months prior to the rash onset; there were otherwise no changes in her medication regimen. The exam showed hyperpigmented brown scaly plaques with central atrophic patches on the conchal bowl of the ears Figure , violaceA 4-mm punch biopsy of a representative lesion from the medial knee was performed. Histopathologic findings suggested early SCLE and consisted of basilar vacuolar degeneration with scant dermal perivascular lymphocytic infiltrate Figure . ColloidCLE comprises three subtypes for which no standardized classification criteria exist . The SCLThere is significant histologic overlap between CLE phenotypes, and their differentiation on the basis of histology alone is unreliable. Common CLE findings include interface dermatitis with mononuclear cell infiltrate at the dermoepidermal junction, basal cell degeneration, perivascular and periadnexal inflammation, dermal mucin deposition, and hyperkeratosis . A superAs SCLE is rare in African Americans , our patMoreover, it is possible that her new-onset SCLE was related to the recently initiated apixaban therapy. Drug-induced SCLE (DI-SCLE) is clinically as well as serologically indistinguishable from the idiopathic form and can occur days or years after drug initiation . Unlike A wide range of drugs have been associated with DI-SCLE; however, direct oral anticoagulants are rarely implicated. McCarthy et al. have published a case of rivaroxaban-induced SCLE, which presented with typical clinicopathologic features three weeks after the drug administration and resolved within four months of drug discontinuation and concurrent topical corticosteroid therapy . RecentlWe presented a patient with SCLE with newly diagnosed SLE. Our patient displayed features spanning the lupus erythematous spectrum, which along with atypical findings makes this case unique and equally informative. It is important to emphasize that the hypothesized relationship between our patient’s ethnicity and photoprotected SCLE distribution, as well as the possible association between apixaban and DI-SCLE, are both merely speculative and require further investigation.


A best evidence topic has been constructed using a described protocol. The three-part question addressed was: In patients with Infrarenal abdominal aortic aneurysm (AAA), Does endovascular abdominal aortic repair (EVAR), AS compared to open surgical repair (OSR), has lower secondary rupture rates? The outcomes assessed were the secondary rupture rate in both techniques. The best evidence showed that The OSR has statistically significant lower secondary rupture rates than the EVAR. •Endovascular abdominal aortic aneurysm repair is inferior to the open surgical repair regarding the secondary rupture rates.•Long term outcomes of the open surgical repair are better than the Endovascular repair.•Secondary rupture is more common in endovascular repair than the open surgical repair of abdominal aortic aneurysm. This fo2After resuscitating a 70-year-old man who presented to the emergency department (ED) with haemorrhaogic shock due to secondary rupture after open repair of infrarenal abdominal aortic aneurysm, one of the ED registrars asked; which modality of AAA repair has lower secondary rupture rates; EVAR or Open repair?••[Does EVAR has lower Secondary rupture rates];•[As compared to OSR]?Three Parts Question:3A. Embase 1974 to June 2021 using the OVID interface: [AAA OR Abdominal Aortic Aneurysm]AND [Open repair OR open surgical repair OR OSR] AND [EVAR OR Endovascular Repair] AND [Secondary rupture]•Inclusion criteria: all original articles that review the secondary rupture rate among patients with AAA who underwent open surgical repair vs Endovascular Repair.•Exclusion criteria: case reports, systematic reviews, letters to the editor, conference abstracts.B. Medline using the PubMed interface: [AAA OR Abdominal Aortic Aneurysm]AND [Open repair OR open surgical repair OR OSR] AND [EVAR OR Endovascular Repair] AND [secondary rupture]. The results were limited to English articles and human studies. 4A total of 853 papers were found using both search engines. We excluded 812 papers because they were irrelevant based on the titles and abstracts. Forty-one full-text articles were screened and assessed for eligibility. From these, six papers were identified to provide the best evidence to answer the question.5The search results are summarized in 6Endovascular repair of abdominal aortic aneurysm repair has increased worldwide. It has become a powerful alternative to open surgical repair since Juan C. Parodi did the first successful endovascular repair in 1991 . This isIn this article, we have reviewed the best studies which compared the open repair to the endovascular repair considering only the secondary rupture after the primary repair and any pre-interventional rupture were excluded.All the five studies in our review reported statistically significant Lower secondary rupture rate difference in the OSR than the EVAR group. Three of them were Randomized controlled trials which were conducted by Lederle FA et al. , Van Sch7According to the above articles, the best evidence shows a statistically significant lower secondary rupture rate among patients with open surgical repair of abdominal aortic aneurysm in comparison to endovascular repair.Ethical approval was not required.No source of funding.Ahmed Abdel Rahim (AA): Conducted the literature search and wrote the paper.Rashid Ibrahim (RI): Assisted in the literature search and Writing of paper.Lu Yao(LY): Editing of writing.Ahmed Khalf (AK): Assisted in writing of paper.Mohammed Ismail (MI): Assisted in the literature search and writing of paper.1. Name of the registry:2. Unique Identifying number or registration ID:3. Hyperlink to your specific registration (must be publicly accessible and will be checked):Ethics committee approval was not required as the study was review of previously done studies.Ahmed Abdel Rahim.No conflicts of interest.