Cholinergic regulation of hippocampal theta rhythm has been proposed as one of the central mechanisms underlying hippocampal functions including spatial memory encoding. However, cholinergic transmission has been traditionally associated with atropine-sensitive type II hippocampal theta oscillations that occur during alert immobility or in urethane-anesthetized animals. The role of cholinergic regulation of type I theta oscillations in behaving animals is much less clear. Recent studies strongly suggest that both cholinergic muscarinic and nicotinic receptors do actively regulate type I hippocampal theta oscillations and thus provide the cholinergic mechanism for theta-associated hippocampal learning. Septal cholinergic activation can regulate hippocampal circuit and theta expression either through direct septohippocampal cholinergic projections, or through septal glutamatergic and GABAergic neurons, that can precisely entrain hippocampal theta rhythmicity. The hippocampus has been widely accepted as the brain region for memory encoding and short-term memory storage. The hippocampus receives major excitatory inputs from entorhinal cortex and sends the major output back to the entorhinal cortex ,2. The hSeptal cholinergic and GABAergic inputs to the hippocampus have been traditionally deemed as the pacemakers of theta oscillations, providing rhythmic excitatory and inhibitory hippocampal inputs, respectively . HoweverThere is strong evidence supporting cholinergic involvement in not only type II theta but also type I theta. Several studies have observed elevated septal cholinergic firing rate or hippocampal acetylcholine (ACh) release during both type I and type II theta dominant behavioral states ,21,22,23Both hippocampal muscarinic and nicotinic receptors may contribute to theta regulation ,26,27,28Calcium imaging studies showed that calcium activities in dorsal CA1 pyramidal neurons are high during theta states including active exploration and REM sleep, and low during non-theta states including quiet wakefulness and slow wave sleep. Systemic or local hippocampal administrated mAChR antagonist scopolamine significantly reduced calcium activities in pyramidal neurons . Higher MSDB is indispensable for both type I and type II theta generation and has been proposed as the host of theta pacemakers ,47,48. TOther than septal GABAergic neurons, septal glutamatergic neurons can also regulate theta frequency. Rhythmic optogenetic activation of local septal glutamatergic neurons lineally entrained hippocampal type I theta frequency in behaving mice in the 6–10 Hz range but had little effect on peak theta power . Septal Although direct optogenetic activation of septal cholinergic neurons only had mild effect on type I theta , septal cholinergic activation can still regulate theta through septal GABAergic and glutamatergic neurons, or through direct septohippocampal cholinergic pathway. Systemic or intraseptal administration of atropine mildly decreased type I theta frequency in freely moving rats ,51. The In addition to theta oscillations, there are gamma oscillations in the hippocampus with a frequency ranging from 25 to 100 Hz . Gamma oRecordings from the CA1 area of freely moving mice show that gamma activity is amplitude-modulated at θ frequencies. This theta-gamma coupling is stronger during active exploration than during awake immobility. Intraperitoneally administrated atropine increased theta irregularity, reduced gamma power and theta-gamma coupling during explorative behavior . Stronge+ current [The mechanism underlying this cholinergic modulation of theta-gamma coupling is not clear. Studies suggest that hippocampal interneurons are critical for gamma generation. Slow gamma is driven by interneurons that are activated by CA3 inputs, while fast gamma is driven by interneurons activated by medial entorhinal cortical inputs ,74,76,87 current . Gamma a current , suggestSeptal cholinergic neurons are activated during both type II and type I theta states. Cholinergic activation can regulate hippocampal theta through both direct septohippocampal cholinergic pathway and indirect local septal circuit . ElevateLocal septal cholinergic action is essential for type II theta generation but is less important for type I theta and usually only has a moderate effect on type I theta frequency regulation. The relationship between type II theta centered on septal hippocampal loop and type I theta centered on the entorhinal hippocampal loop is currently unclear. Some researchers consider that type II theta coexists with type I theta in behaving animals and is only unmasked by anesthesia administration. It is also possible that each type of theta only occurs during its preferential states. Even if type II and type I theta coexist in behaving animals, it is still not clear if and how they are integrated to modify various aspects of behavior outcomes. Current studies seem to suggest that type II theta is more related to internal drive arising from past experiences, and type I theta is more related to external drive arising from ongoing activities.Cholinergic transmission can target both glutamatergic and GABAergic neurons in MSDB and the hippocampus through both mAChRs and nAChRs. It is currently unclear if septal cholinergic activation directly regulates septal GABAergic neurons or indirectly through local glutamatergic neurons, or both, and what cholinergic receptor subtypes underlie such mechanisms, respectively. An Intersectional Recombinases-mediated Area-and-cell-Specific gene Excision (IRASE) method has recently been developed to achieve receptor knockout with spatial and cell-type specificity . In this


Urothelial cancer is a difficult type of tumour entity. It may be harmless and easily treated, it can be bothersome with constantly recurrent disease affecting quality of life and it is lethal once progressed to metastatic disease. The course of this disease may be assumed but often is not anticipated. Treatment algorithms vary from office-based tumour fulguration over cystectomy and or nephroureterectomy to complex systemic therapy. During the past years new treatment options have been developed such immunotherapy or drug conjugates hereby increasing life expectancy in a still deadly disease.Although guidelines have been blown up with information, still there is lack of knowledge in many cases. Examples? We used to treat urothelial cancer with predominant neuroendocrine component with primary chemotherapy but most patients only survived months after cystectomy. Changing to early cystectomy in low volume disease has provided better results. A young woman with pulmonary metastases has not responded to chemotherapy or immunotherapy. After several surgical treatments she achieved long term recurrence free disease. A patient had massive urothelial tumours in both upper tracts and in his bladder but never developed metastases. Every Urologist and Uro-Oncologist has similar stories to tell. These are patients we learn from each other but you will never find answers within guidelines as they rely on randomized controlled trials or at least on big cohort studies.The reader of this issue may find some answers that have not been told. Therefore, I encourage everyone to read through the following articles:Sharma et al. present the rare case of a 19-year-old male with advanced urothelial carcinoma of the bladder. They performed whole-exome sequencing to identify potential treatment targets hereby presenting potential driver mutations and raising the question whether mutations in genes involved in ion channels may be engraving tumours.Xu et al. A patient with neuroendocrine carcinoma of the ureter colliding with squamous cell carcinoma is discussed respecting current literature of only 16 previous cases worldwide. In this case the combination of surgery and systemic therapy (cisplatin/etoposide) has provided prolonged survival. Another small cell neuroendocrine carcinoma case is presented by Qing et al. They describe the rapid disease progression despite surgery and adjuvant systematic therapy including PD-L1 immuno-checkpoint inhibition (ICI) combined with radiotherapy.Another highly interesting case is reported by Li et al. administered the PD-1 inhibitor Tislelizumab that showed remission in an isolated renal calyceal urothelial carcinoma. Zan et al. used the PD-1 inhibitor Toripalimab combined with the multi-targeting tyrosine kinase inhibitor Anlotinib in last line sequence which resulted in long-term clinical response for over 25 months in a patient with metastatic disease.Systemic treatment of urothelial cancer consists of platinum-based chemotherapy and ICI therapy. Up to date, the antibody-drug conjugate Enfortumab vedotin has been approved by FDA and EMA for treatment after failure of the two previously mentioned therapies. Especially the use of immuno-checkpoint inhibitors may lead to long-term survival in metastatic urothelial carcinoma which has rarely been described before. New checkpoint inhibitors have been developed and are now increasingly used. Therefore, we present two case reports in which treatment success by using new PD-1 inhibitors are reported. Cai et al. present a case of a 56-year old male patient who developed recurrent disease in the ureteral cutaneous stoma after radical cystectomy. Interestingly they performed a completely intracorporal resection of the tumour and ileal conduit surgery. They describe their procedure step by step.Robot assisted surgery is increasingly used in complex situations. I hope you find this selection of case reports worth reading.The author confirms being the sole contributor of this work and has approved it for publication.


Previous studies have established a connection between higher mindfulness and cognitive abilities; however, few studies have considered the mechanism underlying this relationship. The cognitive benefit of mindfulness may be through reduced fatigue and daytime sleepiness. This study examined if higher, naturally occurring mindfulness is associated with higher subjective cognition and whether lower fatigue or sleepiness mediate this relationship. Two independent samples of nurses (N1=60 inpatient (IP); N2=84 outpatient (OP)) completed 14 days of ecological momentary assessment (EMA). Fatigue/sleepiness, mindfulness, and subjective cognition  were assessed using EMA. The 5-item Mindful Attention Awareness Scale assessed state mindfulness. Multilevel mediations were conducted in Mplus to account for the nested data. At the within-person level, daily subjective cognition was higher than average on days when mindfulness was higher in both OP and IP samples. This association was mediated by lower levels of fatigue  and lower sleepiness . The daily indirect pathways were found after controlling for between-person differences; those with higher mindfulness reported higher subjective cognition through lower fatigue, and this effect was only significant in OP nurses . Results highlight the importance of monitoring momentary mindfulness and intervening on daily fatigue and sleepiness as these may influence one’s subjective cognition and ultimately their objective performance. These findings may help identify modifiable factors to promote quality of care in nurses and their own well-being.


Pulmonary arterial hypertension (PAH) is a rare, progressive disorder. PAH is caused by a wide spectrum of pathologies but the cause remains undetermined on many occasions and patients are classified in the idiopathic group.Here we report a young woman with rare congenital visceral abnormalities presenting with severe pulmonary hypertension.Pulmonary hypertension is a complex disorder. Search for uncommon conditions that lead to pulmonary hypertension is necessary to determine the best management options.The online version contains supplementary material available at 10.1186/s43044-022-00273-x. Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure of 20 mm Hg or greater at rest with the stipulation that pulmonary vascular resistance (PVR) is ≥ 3 Woods units, as evaluated by right heart catheterization. In PH there is pathologic medial hypertrophy, intimal proliferation and fibrotic changes mainly in the distal pulmonary arteries. Remodeling in the pulmonary vasculature leads to right heart failure and progressive decline in functional capacity. The early symptoms of PH are non-specific, and the diagnosis is often made in advanced stages of the disease with worse long-term outcomes . PH assoAn 18-year-old asymptomatic female who was candidate for vaginal reconstruction surgery due to Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome was referred to our tertiary care center following incidental finding of right sided cardiac chamber enlargement and severe pulmonary arterial hypertension in a transthoracic echocardiography performed prior to the gynecologic surgery. The patient had uterine agenesis and primary amenorrhea with normal external genitalia. She showed normal developmental and pubertal milestones. On genetic study she had normal female karyotype of 46, XX. In physical examination there was scoliosis of the spinal bones.Chest X-ray depicted dilated pulmonary artery, right ventricular enlargement and scoliosis Fig. . In twelLaboratory data were negative for autoimmune and rheumatic causes of pulmonary hypertension. We found a relatively low platelet count of 118,000 per microliter of blood plus mild increases in liver enzymes and total bilirubin levels. Although the patient had previously undergone abdomino-pelvic sonography for her gynecologic problems that only reported uterine agenesis, we decided to perform a repeat sonography in search for possible liver abnormalities or portal hypertension with regards to unexplained thrombocytopenia. Interestingly abdominal sonography showed that the portal vein was totally absent and right liver lobe was atrophic.Further evaluation by abdominal CT-angiography revealed congenital absence of intra-hepatic portal branches with direct drainage of abdominal veins to inferior vena cava resulting in extra hepatic porto-systemic shunt in favor of Abernathy type 1 visceral malformation. There was also gut malrotation and evidence of MRKH syndrome with underdeveloped uterus and normal ovaries. Computed tomographic angiography of the heart and pulmonary arteries showed no evidence of pulmonary parenchymal involvement and no chronic pulmonary thromboembolic disease or vascular shunts Fig. .Fig. 3CoRight heart catheterization data confirmed severe pre-capillary pulmonary hypertension with pulmonary arterial pressure of 100/40 mmHg, normal cardiac output, normal capillary wedge pressure and no left to right shunts. Abdominal vascular angiography showed the complete absence of portal vein with splenic and superior mesenteric veins confluence draining directly to inferior vena cava forming a mesentero-systemic shunt  imaging helps delineate cardiac morphology and function and non-invasively assess the hemodynamics. CMR also provides valuable prognostic information. Right heart catheterization is necessary to confirm the diagnosis, ascertain PH severity and carry out vasoreactivity testing when clinically indicated –5.Pulmonary hypertension occurs in about 1–5% of patients with portal hypertension. Abernethy malformation or congenital extra hepatic portosystemic shunt is a rare abnormality of the portal venous system with shunting of portal blood into the systemic venous system. Abernethy malformation has two subtypes. In type I that is more frequent in females, the portal vein and intrahepatic portal circulation are entirely absent. In type II the portal vein is hypoplastic. In the absence of portal venous system the intestinal and splenic veins drain directly to the inferior vena cava, left renal vein or the left hepatic vein creating a porto-systemic shunt and varying degrees of portal hypertension. As the normal enterohepatic circulation is diminished, the toxins and vasoactive material from the intestine are bypassed to the systemic circulation without being metabolized in the liver leading to liver damage, hepatopulmonary syndrome, pulmonary hypertension and arterio-venous fistulas. Pulmonary arterial hypertension develops as a result of chronic vasoconstrictive effect of toxic vasoactive substances on the pulmonary vascular bed. There is also an increased risk of hepatic neoplasms. Type II could be treated by surgery or interventional methods of shunt elimination –8. Our pSkeletal and visceral anomalies including hepatobilliary, splenic and genitourinary anomalies have been reported in Abernethy malformation . Our patPulmonary hypertension is a complicated and multifactorial disorder requiring multidisciplinary assessment. Search for unusual and rare conditions that may cause pulmonary hypertension including congenital visceral abnormalities is important in determining the prognosis and treatment.Additional file 1: Abdominal vascular angiography showing  absence of portal vein with splenic and superior mesenteric veins confluence draining directly to inferior vena cava.


Intensive professional training is widely used in modern organizations, as it helps employees adapt to dynamic work and technology changes . Relaxation techniques may reduce the negative effects of intense learning processes . They can also enhance the productivity of the training itself by helping to achieve optimal states for the completion of learning goals.Our study concerns differences in mastering relaxation techniques by employees of younger and middle-age groups during intensive professional training.Sample - 62 employees, participants of communication training. The 15-min session of progressive relaxation combined with autogenic formulae was conducted after 5 hours of intensive training. Measures: standard psychological and physiological functional state tests ; an information perception task.The efficiency of the relaxation techniques varied between different age groups: younger participants (aged 20-30) were more successful in managing both tasks – learning new relaxation skills and achieving deeper rest . They were also more prepared for completing the information perception task (they made less mistakes). Older participants (aged 30-50) experienced more difficulties with the new relaxation skills and used relaxation primarily to restore their psychophysiological resources, rather than to prepare for the upcoming training task.The results showed that relaxation techniques provide a system optimization effect on the participants of intensive training programs, though participants’ individual differences  should be taken into account when planning the outcomes of such interventions.No significant relationships.


A 74-year-old female with previous permanent pacemaker insertion for complete heart block and no history of connective tissue disease presented to our regional cardiothoracic center with progressive exertional shortness of breath. Nine years later, when the patient was 83 years old, a computed tomography scan of the thoracic aorta revealed an isolated aneurysm of the aortic root measuring 7.6 × 5.1 cm at the sinus of Valsalva. A 74-year-old female with previous permanent pacemaker insertion for complete heart block and no history of connective tissue disease presented to our regional cardiothoracic center with progressive exertional shortness of breath. Transthoracic echocardiogram (TTE) confirmed severe calcific aortic stenosis associated with a pseudo-bicuspid aortic valve, and coronary angiography  showed aNine years later, when the patient was 83 years old, a surveillance transthoracic echocardiogram suggested aortic dilatation. A computed tomography (CT) scan  of the tThe case was discussed at our departmental aortic multidisciplinary team meeting. Owing to the patient’s generalized frailty and the perceived perioperative risks associated with repeat surgery, conservative management was advised with ongoing medical follow-up.Judicious clinical assessment combined with periodic echocardiographic surveillance following surgical valve intervention is essential to monitor residual or concurrent non-intervened valve disease. As demonstrated in this case, such an approach can also identify novel pathologies affecting the heart and great vessels, permitting their operative management where appropriate. Although the delayed aortic root expansion following aortic valve replacement is well documented, the prophylactic replacement of the aortic root when not significantly dilated (< 45 mm) is not justified by current guidelines in non-aortopathy populations.


True Luminal A breast cancer represents an endocrine sensitive, surgically curable disease that does not mandate systemic chemotherapy as part of the management paradigm. This disease is reliably identified by a Recurrence Score (RS) < 25 using the OncotypeDX© 21-gene expression assay . RegrettAdditionally, this conclusion from the RxPONDER trial lags considerably behind the de-escalation of surgery in early-stage breast cancer: There is a habitual tendency to prescribe untargeted chemotherapy in Luminal A breast cancer to improve survival, perhaps lessons could be learned from trials conducted in the advanced setting. In the recent MONALEESA-7 and PALOMA-3 trials, the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to conventional endocrine agents enhanced survival for premenopausal women with metastatic Luminal A disease. Moreover, evidence from the SOFT and TEXT trials illustrate that adjuvant tamoxifen alone is appropriate for most premenopausal patients with early-stage disease, while absolute improvements of 10–15% observed in ‘high recurrence risk’ patients using ovarian suppression and exemestane versus tamoxifen alone. While it is unsurprising that CET prescription improves outcomes in premenopausal women, the oncological outcome observed from these targeted therapies far supersede the reported absolute benefit from CET described in the RxPONDER trial , 3. WhilThe molecular insights from Paik et al. revealed the etiology of the small benefit in NSABP B-20 and prevented the perpetuation of the ongoing inappropriate therapeutic strategy . TranslaOverall, the conclusion from this piece is quite simple: A treatment strategy that involves chemotherapy for patients with a RS < 25 risks the prolongation of a fallacy that opposes the scientific reasoning supporting personalized appropriate treatment strategies for breast cancer. A translational approach may help to minimize recurrence, maximize quality of life, and build on the novel insights gleaned from the molecular era. The next phase of neoadjuvant translational research trials must focus on deciphering the relatively small proportion of premenopausal patients with RS < 25 who are a recurrence risk and optimize the therapeutic strategy appropriately. Surely, we cannot prolong the suboptimal care of this generation or expose our prospective patients to untargeted toxic therapy which is neither justified nor effective for the majority.


Adaptive thinking demands a balance between manifestations of intrapsychic activity and reliance on requirements of the outer reality. Features of responses to Rorschach’s III card could provide information about subject’s ability to preserve the dialectical tension between the two poles of external and internal realities during solving tasks related to interpersonal relationships.To compare reality-fantasy relations during Rorschach’s III card responding in patients with schizophrenia, neurocognitive impairment and normal subjects.Participants were 12 young adult inpatients with schizophrenia, 14 students without mental disorders and 12 inpatients with neurodegenerative diseases of old age. Reality-Fantasy Scale (RFS) was applied to assess responses to Rorschach’s III card. RFS scale ranges from –5  to 5  .Patients with schizophrenia  demonstrated tendency to fantasy domination  if compared with the students . Patients with neurodegenerative diseases , conversely, had difficulties to apply fantasy during solving Rorschach task .Express Rorschach testing using III card could be useful to provide screening data of thinking tendencies related to situations of social interaction. Also it provides a mental pabulum regarding role of cognitive impairment in schizophrenia in relation to significance of affective dependence of their thinking process.The reported study was funded by RFBR, project number 20-013-00772


A 52-year-old man presented with temporal haemoptysis and chest pain 6 months after radiofrequency catheter ablation for atrial fibrillation. Computed tomography revealed severe stenosis in the left upper pulmonary vein (PV) and complete occlusion of the left lower PV. A modified sutureless repair of the left PV obstruction was successfully performed. This modified procedure provides a feasible, safe and effective means of treating PV obstruction, even in cases with distal extension of stenosis. The incidence of pulmonary vein (PV) stenosis following radiofrequency catheter ablation of atrial fibrillation is ∼1% [1]. The incidence of pulmonary vein (PV) stenosis following radiofrequency catheter ablation of atrial fibrillation is ∼1% , 3. SeveA 52-year-old man diagnosed with temporal haemoptysis, chest pain and low-grade fever was admitted to our hospital. He had undergone radiofrequency catheter ablation for atrial fibrillation 6 months earlier. Computed tomography revealed multiple patches of consolidation in the left lower lobe with minimal pleural effusion Fig. A. Three-Cardiopulmonary bypass was established under general anaesthesia via median sternotomy. Cardiac arrest was observed by antegrade cardioplegic perfusion. Moderate hypothermia at a nasopharyngeal temperature of 28°C was applied to obtain a bloodless operative field, in combination with a blower using carbon dioxide. Left upper and lower PV lesions were identified after the heart was retracted to the right. The left lower PV and its branches were peripherally dissected beyond the pericardial cavity because of a lesion that was widely obstructive due to fibrous thickening. The left atrial appendage was longitudinally incised from the apex and then separately extended towards the upper and lower PVs beyond the lesion Fig. C. The paA high rate of restenosis is associated with interventional therapy with or without stent placement for iatrogenic PV stenosis post-catheter ablation procedures (3). Surgical repair represents an alternative option stemming from congenital PV malformation surgery experience, where the sutureless technique is a well-established treatment . This teIn this case, the left lower PV required distal dissection beyond the pericardial cavity because of a widely obstructive lesion. In the sutureless technique, the extra-pericardial cavity was closed using a bovine pericardial patch. This procedure did not apply stress to the PV incision line. Moreover, the peripheral PV orifice was protected via the overlying flap. We anticipate a low risk of pseudoaneurysm formation with this technique in view of normal intracardiac pressures. Direct oral anticoagulation is planned for at least 6 months after surgery. Long-term follow-up is warranted as restenosis is a well-recognized complication. This modified procedure provides a feasible, safe and effective means of treating PV obstruction, even if the lesion extends distally to the peripheral branches.Conflict of interest: none declared.Interactive CardioVascular and Thoracic Surgery thanks Steven Hunter and the other anonymous reviewer(s) for their contribution to the peer review process of this article.


Hearing loss is highly prevalent but disparities exist in hearing care. Delivering care in partnership with community health workers (CHWs) is an established approach to addressing disparities but has not been robustly studied in hearing care. We recruited older adults with hearing loss from community sites in Baltimore, MD. The 2-hour intervention consists of fitting a low-cost amplification device and counseling.151 participants were randomized. The primary outcome was change in communication function . Communication function significantly improved in the intervention group, with an intention to treat estimated average treatment effect of a -12.98 point change . In the first randomized control trial of a CHW-delivered hearing care intervention for older adults using low-cost amplification devices, participants receiving the intervention demonstrated a treatment effect comparable to prior studies of conventional hearing aids fit by audiologists.


J Transl Med [HPV Selfy assay  fulfils international validation criteria for hrHPV testing on clinician-collected cervical samples (Meijer guidelines) [In primary cervical cancer screening, it is crucial to use only hrHPV tests that are clinically validated according to international guidelines in order to reduce the risks of missing relevant disease and of over-treatment. In the recent ansl Med  paper, Adelines)  as well delines) . Our perHPV Selfy (index test) [Validation requires an appropriately composed study population comprising a sufficient number of diseased subjects, derived from a continuous screening population or from a clearly described selection of CIN2+ cases and < CIN2 controls . Avian eex test) , but it ex test) . This maex test)  and confHPV Selfy on self-samples was non-inferior to clinician-collected samples was flawed by critical statistical errors. The number of subjects with discordant self+ /clinician− and self−/clinician+ results  in the HPV Selfy assessment [Collaborations between science and industry are instrumental to advance clinical research, however contractual independency of researchers and autonomy of publication enhance scientific credibility. We observe that sixteen of thirty six authors (including the first and last) of the JTM paper are affiliated with the manufacturer of the assay. In the 2020 list of validated HPV assays , assays sessment . We reco


Optic nerve infiltration as the first sign of isolated central nervous system relapse of acute lymphoblastic leukemia (ALL) is rare. A seven-year-old girl with standard-risk B-cell ALL who was in remission presented with sudden onset of left eye pain and loss of vision. Examination revealed no perception to light in the left eye with positive relative afferent pupillary defect. The optic disc was hyperemic and swollen with total obscuration of the disc margin associated with central retinal artery and vein occlusion. Magnetic resonance imaging of the brain and optic nerve showed left intraorbital optic nerve thickening associated with perineural enhancement and intraconal fat involvement.Lumbar puncture revealed leukemic infiltration with blast cells after a week of eye symptoms, while bone marrow aspiration was negative for malignant cells. A diagnosis of left leukemic optic nerve infiltration with central retinal artery and vein occlusion was made. A high index of suspicion with repeat cerebrospinal fluid sampling is crucial to confirm the diagnosis as vitreous biopsy may fail to reveal infiltrative cells. Optic nerve involvement is reported to occur in one-sixth to 34% of leukemic cases ,2. HowevThis article was previously presented as a meeting poster at the 33rd Asia-Pacific Association of Cataract & Refractive Surgeons (APACRS)-Singapore National Eye Centre (SNEC) 30th Anniversary Virtual Meeting on July 30-31, 2021.A seven-year-old girl with standard-risk B-cell ALL diagnosed two years ago who had completed her systemic and prophylactic intrathecal chemotherapy and was in complete remission for two months presented with sudden onset of left eye pain and loss of vision. It occurred upon awakening from sleep and was associated with throbbing headaches. She did not have any complaint over the right eye. She had no history of hyperleucocytosis, extramedullary disease, or CNS involvement during her first diagnosis of ALL. Systematically, there was no preceding fever or signs of systemic infection.Her left visual acuity was non-perception to light with positive relative afferent pupillary defect. Right visual acuity was 3/3 on the Sheridan Gardiner test. Anterior segment was unremarkable in both eyes. Left eye fundus examination revealed a markedly swollen, hyperemic optic disc bulging into the vitreous with total obscuration of the disc margin. Retinal veins appeared very dilated and tortuous with presence of pale, edematous macula and retina. There were flame-shaped intraretinal hemorrhages in all four quadrants with vitreous hemorrhage inferiorly. There were no cotton wool spots Figure , Panel BAn urgent magnetic resonance imaging (MRI) of the brain and optic nerve showed left intraorbital optic nerve thickening associated with perineural enhancement and intraconal fat involvement Figure . The rigFundus fluorescein angiography revealed a complete absence of choroidal, retinal artery, and venous filling of the left eye for up to seven minutes while the right eye showed leakage from the optic disc  and initial lumbar puncture (LP) were negative for malignancy. Second LP was done a week later together with anterior chamber tapping and vitreous biopsy. Cerebrospinal fluid cytology showed presence of blast cells, suggestive of leukemic infiltration of the CNS Figures , 3B. AntIn view of relapse of leukemia with isolated CNS involvement, she was started on reinduction chemotherapy UK ALL R3 including intrathecal methotrexate. Neither local ocular chemotherapy nor radiotherapy was initiated. To date, her left eye remains without perception to light with right eye vision maintained without deterioration to date.ALL is an aggressive malignant proliferation of lymphoblasts with peak prevalence between the ages of one and four . It can Optic nerve is known to be a sanctuary for leukemic cells which is relatively unaffected by systemic chemotherapy and even intrathecal chemotherapy . Cases oIn our case, despite intrathecal chemotherapy, which was given for CNS prophylaxis at the first diagnosis of ALL, and achieving complete remission after completion of chemotherapy, she developed isolated CNS relapse.The majority of patients with CNS relapse present with symptoms such as altered mental status, headache, and cranial nerve palsy while only a minority (6.5%) report blurred vision as the initial complaint . This waRosenthal classified optic nerve infiltration in leukemia into prelaminar and retrolaminar . In prelThere are limited cases reported on central retinal vascular occlusion in ALL in contrast to other lymphoproliferative disorders such as lymphoma -12. A caA review by Myers et al. found that malignant cells are identified in the cerebrospinal fluid in a majority of leukemic infiltration cases . In our Vitreous biopsy has value in diagnosing a leukemic relapse when there is presence of dense vitreous cellular infiltration . Shenoy Optic nerve infiltration may be the only initial presentation indicating relapse of ALL following attainment of disease remission. A high index of suspicion and prompt diagnosis may not only avoid irreversible loss of vision but more importantly can be life-saving for the patient. Repeated cerebrospinal fluid analysis may be necessary in the event of initial negative results for malignancy.


We present a case of a 68-year-old man who presents with worsening cough and dyspnoea 12 months after undergoing radiofrequency ablation therapy for atrial fibrillation. Investigation revealed complete occlusion of the left lower pulmonary vein and partial stenosis of the left upper pulmonary vein. He underwent a stage surgical resection with the first stage being a left lower lobectomy for the non-viable lobe followed by a repair of the left upper pulmonary vein via anastomosis with the left atrial appendage. This staged procedure yielded excellent results and avoided the need for a left-sided pneumonectomy. The formation of pulmonary vein stenosis following radiofrequency ablation (RFA) therapy for patients with atrial fibrillation (AF) is a recognized complication. The mechanism of stenosis formation can occur in either the early or late post procedural phase. It is driven by myocardial necrosis and this acute inflammatory process can promote thrombus formation in the early stage. Late-stage stenosis results from the fibrotic changes associated with myocardial fibrosis that can also involve the pulmonary veins which leads to venous contraction and stenosis.We present a case of staged repair of a left upper and lower pulmonary vein stenosis which formed secondary to percutaneous RFA which preserved the functional left upper lobe and avoided the need for a left pneumonectomy.A 68-year-old man with a history of refractory paroxysmal AF and severe left ventricular dysfunction underwent catheter-guided percutaneous RFA. After initial improvement in symptoms and left ventricular (LV) function, over a period of 12 months the patient developed persistent cough and worsening exertional dyspnoea presenting with NYHA III symptoms.Repeat transthoracic echocardiogram demonstrated no deterioration in left ventricular function to coincide with symptom progression. A computed tomography (CT) chest demonstrated patchy infiltrates in the left lower lobe and a small pleural effusion. After multi-disciplinary team (MDT) presentation, a dedicated CT pulmonary vein study was obtained demonstrating pulmonary vein stenosis of the upper left pulmonary vein and complete occlusion of the lower left vein. A ventilation perfusion (V/Q) scan confirmed the lower lobe to be non-functional but the upper lobe still viable. A staged procedure was planned to avoid the need for a pneumonectomy.The patient underwent a staged left lower lobectomy and pulmonary vein repair as a staged procedure. The left lower lobe was resected as a video-assisted thoracoscopic procedure. Intraoperatively, the left lower lobe was oedematous with dense inflammatory adhesions to the chest wall. During the lobectomy, the left upper pulmonary vein was dissected in preparation for the planned upper pulmonary vein repair. Histopathology confirmed the left lower lobe to be necrotic .The patient was returned to the operating room 3 days later to undertake repair of the left upper pulmonary vein stenosis via sternotomy. The patient was placed onto cardiopulmonary bypass using antegrade Del Nido cardioplegia. Opening of the left atria revealed a circumferential stenosis of the left upper pulmonary vein. The vein was stapled at the left atrial junction and then trimmed off. The left atrial appendage was opened, several minor trabeculations were resected and the left upper pulmonary vein anastomosed to the appendage . When weCatheter RFA is an effective treatment modality for both permanent and paroxysmal AF in patients who have been unsuccessfully treated with antiarrhythmic drug therapy . RandomiPV stenosis can be managed with balloon dilation or venous stenting. Both procedures carry a risk of restenosis with rates of >50% balloon dilation and > 25% reported . Early i


Credentialing in GI endoscopy is not a universally standardized process. National guidelines may provide a framework for local training, however in certain settings, training committees set minimal competency requirements that must be met before a clinician can be accredited to practice independently. There is a paucity of literature assessing the inter-societal and geographic variability in guidelines and training requirements in endoscopy.To systematically review the available credentialing guidelines proposed by different GI endoscopy societies and affiliated training committees internationally.We conducted a systematic review according to the PRISMA guidelines. A comprehensive literature search was performed for credentialing guidelines for GI endoscopy from inception until January 2022. Two reviewers screened and one reviewer abstracted data using a pre-defined data collection form.From the 653 records obtained from our search, 20 credentialing guidelines from 12 different GI societies were ultimately included in the review. These guidelines encompassed the following procedures and outlined the following key-performance indicators; a) Colonoscopy: the recommended minimum number of procedures performed ranged from 150-275 with a minimum cecal intubation and adenoma detection rate of 85-90% and 20-30% respectively; b) EGD: the minimum number of procedures prior to credentialing ranged from 130-1000, the minimum duodenal intubation rate ranged from 95-100%, and the range for minimum number of upper GI bleeds managed was 20-45 ; c) ERCP: the recommended minimum number of procedures prior to credentialing ranged from 100-300 cases with a minimum selective duct cannulation rate of 80-90%. Guidelines for flexible sigmoidoscopy, EUS and capsule endoscopy were also obtained.There is a general concordance amongst the various international GI societies with regards to minimum procedural volume and performance in key procedural tasks prior to credentialing, however the use of validated education assessment tools was lacking in the majority of guidelines. Additional KPI’s need to be explored for less routinely performed procedures such as EUS and capsule endoscopy.NoneNone Declared


Prior work suggests that more frequent or higher exposure to stressors relates to less positive affect and more negative affect in daily life. Limited knowledge exists about whether subjective appraisals of such stressors  also have negative links to daily well-being. This study examines this link using data from an 8-day daily dairy study (n=675 days) in an online sample of older adults . We also explored potential psychological moderators particularly relevant to the experience of aging . Results from multilevel models indicate that people reported more negative affect and less positive affect on days with more negative appraisals, especially on those days when they also had more negative self-views of aging. These findings highlight S-VOA as psychological resources that help people cope with stressful events in everyday life.


She is currently receiving the ICE  regimen for persistent Langerhans cell sarcoma (LCS). This case highlights the phenomenon of transdifferentiation, in which neoplastic B cells are thought to convert to a histiocytic or Langerhans cell phenotype via unknown mechanisms. The case also highlights the value of histopathologic examination of multiple biopsy specimens for accurate diagnosis and design of a treatment plan in patients in whom PET/CT shows dichotomous SUV values.A 31‐year‐old woman presented with abdominal pain and a recent history of chest pain and B symptoms. Physical examination showed lymphadenopathy on left side of face/upper neck and mild splenomegaly. Laboratory workup showed microcytic hypochromic anemia , and elevated serum lactate dehydrogenase of 366 U/L. Positron emission tomography/computed tomography (PET/CT) imaging showed dichotomous


Iatrogenic aortic dissection is a rare but potentially fatal complication of percutaneous coronary intervention (PCI). Iatrogenic aortic dissection following PCI is rare with most cases reporting dissection originating within the coronary vessels with propagation into the ascending aorta. In this specific case, dissection was without coronary involvement, with dissection extending from the ascending aorta into the descending aorta and iliac vessels. Although PCI via radial approach is associated with fewer vascular complications than with femoral approach, significant adverse outcomes may still occur and require prompt intervention. This case highlights the highly atypical presentation of iatrogenic aortic dissection following cardiac catheterization presenting as acute limb ischemia. In such patients as with ours, immediate surgical intervention is necessary with overall poor prognosis. Iatrogenic aortic dissection (IAD) secondary to PCI may present variably and without prompt diagnosis and intervention, while outcomes may be unfavorable. Percutaneous coronary intervention via radial approach has been associated with reduced complications and bleeding rates when compared with femoral approach; however, features associated with radial approach may predispose patients to aortic dissection with coronary involvement. We present the rare case of extensive type A aortic dissection extending into the descending aorta causing limb ischemia following right radial heart catheterization.We present a 56-year-old male with past medical history of coronary artery disease status post-PCI ×2 presenting with chest pain and dyspnea. Labs were remarkable for elevated troponin (1.24 ng/mL), and EKG findings were consistent with NSTE-ACS with ST depression more so within inferior leads. He was medically optimized with ACS directed therapy while troponins continued to uptrend (3.04 ng/mL) overnight. Transthoracic echocardiogram demonstrated normal systolic function (EF: 50-54%) with normal aortic root diameter (3.4 cm) and aortic valve function. Right radial arterial area was prepared, and a 5-French Tiger catheter was used to perform the right coronary angiography. Catheter was unsuccessful in engaging the left coronary artery despite multiple attempts and therefore was replaced with a 6-French JL4 diagnostic catheter, and left coronary angiography was performed. Left heart catheterization was remarkable for significant 80% stenosis of the mid left anterior descending artery (LAD). For the PCI part of the procedure, the EBU 4, 6-French guide catheter was used to support and engage the left coronary artery, and the 0.014 runthrough wire was used to cross the lesion and parked distally. The target lesion at the mid LAD was predilated using the 3.0 × 20 mm Emerge compliant balloon with sequential inflation followed by the placement of a Boston Scientific Synergy 3.5 × 48 mm drug-eluting stent from proximal to mid LAD. Post-PCI results were satisfactory with TIMI grade 3 flow and without dissection of left main and other coronary arteries . Within Radial approach has gained significant interest and usage within interventional cardiology. One of the more significant aims of this approach includes decreasing bleeding and postoperative complications. Comparisons between percutaneous angioplasty using radial and femoral approach showed similar clinical outcomes with decreased access site complications using radial approach . DespiteWhat makes our patient's case incredibly unique is the extent of dissection from the ascending aorta into the abdominal aorta and run-off vessels affecting the relative organ systems. In this case, the patient's symptoms of severe flank pain and lower extremity paresthesia soon after PCI were the only emergent signs of the underlying complication. Imaging confirmed extensive dissection of the abdominal aorta with dissection extending into the left renal, inferior mesenteric, and left iliac arteries causing the relative symptoms in this case. Such cases involving the ascending and descending aorta have high mortality rates and require extensive surgery known as the “elephant trunk” procedure. Our patient was sent to a tertiary medical center where replacement of the supracoronary ascending aorta with arch repair was followed by treatment of the distal aortic aneurysm. Unfortunately, due to this patient's critical condition and extensive dissection, he expired soon after the initial procedure. To the best of our knowledge, this is the first case reporting ascending aortic dissection involving the abdominal aorta and vessels causing limb ischemia using right radial approach. In conclusion, although radial access may hold certain advantages, rare but fatal complications exist which may be more frequent using radial approach. Such complications may be secondary to complex anatomy of the upper extremity vasculature predisposing these patients to catheter-induced trauma and subsequent dissection with supracoronary entry . In suchIn conclusion, although radial access may have certain advantages, rare however significant complications may exist likely secondary to the complex anatomy of the upper extremity vasculature predisposing such patients to catheter-induced trauma. In such cases, immediate recognition and medical management is crucial in avoiding extensive dissection, thereby reducing mortality. To the best of our knowledge, this is the first case reporting extensive aortic dissection involving the abdominal aorta and run-off vessels causing limb ischemia using right radial approach.


Stereolithography based 3D printing of microfluidics for prototyping has gained a lot of attention due to several advantages such as fast production, cost-effectiveness, and versatility over traditional photolithography-based microfabrication techniques. However, existing consumer focused SLA 3D printers struggle to fabricate functional microfluidic devices due to several challenges associated with micron-scale 3D printing. Here, we explore the origins and mechanism of the associated failure modes followed by presenting guidelines to overcome these challenges. The prescribed method works completely with existing consumer class inexpensive SLA printers without any modifications to reliably print PDMS cast microfluidic channels with channel sizes as low as ~75 μm and embedded channels with channel sizes as low ~200 μm. We developed a custom multi-resin formulation by incorporating Polyethylene glycol diacrylate (PEGDA) and Ethylene glycol polyether acrylate (EGPEA) as the monomer units to achieve micron sized printed features with tunable mechanical and optical properties. By incorporating multiple resins with different mechanical properties, we were able to achieve spatial control over the stiffness of the cured resin enabling us to incorporate both flexible and rigid components within a single 3D printed microfluidic chip. We demonstrate the utility of this technique by 3D printing an integrated pressure-actuated pneumatic valve (with flexible cured resin) in an otherwise rigid and clear microfluidic device that can be fabricated in a one-step process from a single CAD file. We also demonstrate the utility of this technique by integrating a fully functional finger-actuated microfluidic pump. The versatility and accessibility of the demonstrated fabrication method have the potential to reduce our reliance on expensive and time-consuming photolithographic techniques for microfluidic chip fabrication and thus drastically lowering our barrier to entry in microfluidics research. Microfluidics is the study and manipulation of fluids at microscopic scales , where micro-scale physics dominate. In recent years, microfluidics has quickly emerged as a crucial tool in several biological and chemical systems, including industrial, clinical, and fundamental research. It has enabled researchers, scientists, and engineers to perform numerous parallel experiments rapidly while consuming minimal reagents as opposed to simultaneously  working with multiple conventional benchtop analytical instruments in a laboratory ,2. MicroConventional microfluidic devices are largely fabricated through microfabrication techniques derived from the Micro-Electromechanical Systems (MEMS) and the semiconductor industry  involvinAlternate microfabrication techniques such as injection molding that enable rapid prototyping also exist ,13 but aIndustrial-grade and research stage 3D printing technologies such as selective laser sintering (SLS)  and Two-Most consumer-grade desktop printers work by splitting a 3D object model into several 2D layers (slicing) and materializing the object out of liquid polymer (melted thermoplastic or liquid resins) layer by layer. The two most common types of printing technology in this space rely either on fused deposition modeling  approach or stereolithography  approach . FDM appOne of the main components of SLA printing is the use of a photopolymerization resin . The priHere we provide application specific strategies that work with ready-made masked stereolithography (MSLA) 3D printing approach to fabricate functional microfluidic chips and microfluidic components. To bring additional functionality into fabricated microfluidic chips, we develop our custom UV curable resins incorporating the combination of high molecular weight Polyethylene glycol diacrylate (PEGDA) and Ethylene glycol polyether acrylate (EGPEA) as the monomer unit to print microfluidic components with tunable mechanical and optical properties. We analyze the range of achievable optical and mechanical characteristics as a function of varying monomer composition in our custom resins. Guidelines are provided to (i) create PDMS casted microfluidic chips generated from MSLA molds (requires plasma bonding), (ii) directly print microfluidic chips with embedded channels using commercial resins (no chip bonding steps required) and (iii) directly print microfluidic chips with embedded channels at a finer resolution and additional functionality using our custom resin formulation (no chip bonding steps). The user can choose either strategy based on their need and resource availability. Finally, we demonstrate further the utility of our custom resin by 3D printing an integrated pressure-actuated pneumatic valve (with flexible cured resin) in an otherwise rigid and clear microfluidic device that can be fabricated in a one-step process from a single CAD file. We also demonstrate the integration of a 3D printed finger actuated microfluidic pumps that can be easily interfaced with the inlet ports of microfluidic devices to move precise amounts of liquids within microfluidic devices without external syringe pumps.We printed MSLA molds with positive extrusion (for PDMS casting) and embedded microfluidic channels using several consumer class desktop MSLA printers including Prusa SL1 , Elegoo Mars 2 Mono and Elegoo Mars 3 Ultra 4k Mono . The feature sets and cost of the printers are specified in The cured 3D parts were carefully taken off the build plate and were immediately submerged and washed with IPA to wash off any residual resin followed by re-rinsing with water to ensure a glossy finish. We found that this extra rinsing step helps in easy pealing of the PDMS from the SLA molds. The parts were then air dried and further cured under Prusa curing station (CW1S) for one minute. For PDMS casting, the PDMS  was poured over the SLA mold with positive features. The PDMS was cured in an oven (50 °C) for four hours. Post curing, inlet and outlet ports were cut into the PDMS followed by bonding it on a clean glass slide in a plasma cleaner  for 30 s. The entire fabrication process-from concept to microfluidic chip-takes ~6 h A.For droplet generation, we used mineral oil  as the continuous phase, and water with blue food dye pigment as the dispersed phase. We used Span 80  as surfactant. Syringe pumps  were used to drive the dispersed and continuous phases at 10 and 100 μL/min respectively. The droplet generator chip and droplets were visualized using an optical microscope . ® high vacuum grease) as a sealant and lubricant. Additionally, a rubber o-ring was added to the tip of the screw to provide an airtight contact between the screw and the microfluidic chip inlet port. The o-ring has an outer diameter corresponding to the diameter of the screw. We found that a syringe plunger gasket can also be used as an alternative to the o-ring for sealing the reservoir. The 3D printed finger actuated screw pump consists of two components-a screw and an inlet port (acting like a liquid reservoir)-that can be tuned to fit virtually any microfluidic device. The inlet port was designed to embed the negative threads to accommodate the screw. We used a standard size (M4–M6) screw thread since they provide several advantages over a custom thread design. The CAD model of the threaded screw can be found online and can be added to the chip design without any major modifications. To prevent liquid leakage due to the tolerances of the printed screws, we used silicone based vacuum grease (Dow Corningn: 700)  as the monomers. We chose Phenylbis  phosphine oxide (Cas: 162881-26-7) (Also known as Irgacure 819) as the photoinitiator and 2-nitrophenyl phenyl sulfide (NPS) (Cas: 4171-83-9) as the UV absorber  = [1:1] + IRG 819 (1% mensions A. While on depth B. Even ton depth A. This d−1). EGPEA monomer shows characteristic peaks at the 750–690 cm−1 and 1490 cm−1 regions corresponding C=C bending and C=C stretching frequencies respectively. PEGDA-700 monomer shows a characteristic broad peak at 1111 cm−1 region corresponding to ester linkage. First, the mixture with equal amounts of the two monomers  retains the characteristic peaks of both EGPEA and PEGDA monomeric resins  for all variations. The resins were printed to form tensile specimens resembling a dog-bone shape to ensure that most of the tensile stress is concentrated in the middle of test specimen  forcing the specimen to break at that region. The setup enabled us to obtain standardized stress-strain profiles for printed parts for a range of resin compositions B. From tcP = lP − aP) which is the pressure differential arising from the difference in pressure of the flowing liquid (lP) in the microfluidic channel and applied pneumatic pressure (aP). The closing pressure then becomes the minimum pressure required to completely close the pneumatic valve and halt the liquid flow in the microfluidic channel  without any modifications to accurately print (i) PDMS casted microfluidic channels with channel sizes as low as ~75 μm and (ii) embedded channels with channel size as low ~300 μm (~200 μm with custom resin formulation). We anticipate these resolutions will only improve in the coming years as the pixel density (ppi) of the new LCD displays continues to increase following Moore’s law trend. Additionally, such printers can also be used to fabricate integrated microfluidic components such as finger-actuated microfluidic pumps and flexible pneumatic microfluidic flow valves. The convenience and swiftness of our proposed technique enable one to go from an “idea stage” to a “functional microfluidic chip” within ~hours as opposed to traditional clean room-based microfabrication (~days), which could drastically lower the barrier to entry in microfabrication and greatly accelerate lab-on-a-chip research.


This study aimed to examine whether neighborhood cohesion would mitigate the adverse effect of living alone on all-cause mortality in community-dwelling older Chinese Americans. Data were drawn from the Population Study of Chinese Elderly , a longitudinal study started in 2011. Mortality was tracked through December 2021 (N = 642 deceased). Cox regression indicated that neighborhood cohesion moderated the association between living alone and all-cause mortality , showing that among participants living alone (N = 678), those with high neighborhood cohesion had a 41% lower mortality risk than their counterparts with low neighorhood cohesion. In contrast, among participants living with others, those with high and low neighborhood cohesion had a similar mortality risk. These findings highlight that strong neighborhood cohesion may protect against the increased risk of premature mortality associated with living alone in older Chinese Americans.


This study aimed to examine potential risk and protective factors for binge drinking among a cohort of 15-16-year-old adolescents in the West of Ireland. This study was a cross-sectional secondary analysis of 4,473 15-16-year-olds who participated in the 2020 Planet Youth survey. Binge drinking was defined as ever consumption of five or more drinks in a two-hour period or less. Data were analysed using SPSS version 27. Multivariable logistic regression was used to examine independent associations between potential risk and protective factors and binge drinking. A p-value of < 0.05 was deemed statistically significant. The prevalence of binge drinking among participants was 34.1%. Female gender  and non-White ethnicity  were associated with reduced odds of ever binge drinking. Self-rated ‘bad/very bad’ mental health , current cigarette use  and current cannabis use  were associated with increased odds of ever binge drinking. Parental supervision  and negative parental reaction to adolescent drunkenness  reduced the odds of ever binge drinking among participants. Getting alcohol from parents was associated with increased odds of ever binge drinking . Adolescents with friends who drink alcohol had almost 5 times higher odds of ever binge drinking . Participating in team sports was also associated with increased odds of ever binge drinking . This study highlights key influences of adolescents’ social environment on their binge drinking, and a need for renewed public health efforts to protect adolescents from alcohol-related harm.• This study identified a high prevalence of ever binge drinking among adolescents in the West of Ireland - this is highly concerning as adolescents are vulnerable to alcohol-related harm.• This study identified factors in the social environment of adolescents associated with binge drinking. This can inform public health action to protect adolescents from alcohol-related harm.


Solo agers are an at-risk population of almost 14 million older U.S. adults currently living alone . Having been independent for most of their lives they often enter older age unprepared for declining health. Even though the numbers of solo agers are rapidly increasing with the aging of the Baby Boomer generation, research remains scant on this population . A mounting concern facing solo agers is finding themselves “unbefriended” . The risk of unbefriended status emphasizes the critical importance of advance care planning; however, many solo agers have no advance directives and factors influencing advance care planning in this group are unclear. In this mixed-methods study, we examined factors influencing advance care planning among solo agers. Survey data were collected from 467 members of a Facebook group for self-identified “elder orphans,” six of whom subsequently participated in qualitative interviews. Among these solo agers, 55% indicated they had advance directives. Hierarchical logistic regression results indicated financial and overall wellbeing predicted having advance directives; however, perceived health risk did not. An interpretive phenomenological analysis of data from six in-depth interviews revealed emergent themes of fears of the future and reluctance to plan for end of life despite acknowledging health risks. Findings can inform policies to meet the growing needs of solo agers who may be at elevated risk of becoming unbefriended.


DOI: 10.1039/C9RA08223A.Correction for ‘Nanoporous hybrid CuO/ZnO/carbon papers used as ultrasensitive non-enzymatic electrochemical sensors’ by Minwei Zhang  The author regrets that the funding information was incorrectly shown in the acknowledgements section of the original manuscript. The corrected funding acknowledgement is as shown below.The author gratefully acknowledges the research facilities provided by the Natural Science Foundation of Xinjiang (No. 2018D01C040).The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


Cognitive Reserve (CR) protects against cognitive decline and dementia but its relation to mobility disability has not been established. To address this important gap in the literature, we conducted a longitudinal investigation to test the hypothesis that higher baseline CR was associated with a lower risk of developing mobility disability in older adults.Participants were dementia-free older adults who received a brain magnetic resonance imaging and had gait speed assessments during follow-up. Using the residuals approach, CR was derived from the modified-Mini-Mental Status Examination (3MS) total score by removing variance accounted for by measures of structural brain integrity, education and race. Mobility disability was defined using a validated cutoff score in gait speed of 0.8 m/s. Logistic regression models using General Estimating Equations (GEE) were utilized to examine longitudinal associations between baseline CR and the risk of developing of mobility disability across repeated assessments.Of the participants  who were free of mobility disability at baseline, 103 developed mobility disability during follow-up (mean=3.1ys). Higher CR at baseline was associated with lower risk of developing incident mobility/disability .We provided first evidence that higher CR was associated with lower risk of developing mobilitydisability in older adults.


Scarce research has examined racial differences in cardiovascular health in the context of social interactions. This study investigated whether (a) friend interactions were associated with better cardiovascular functioning, and (b) such associations vary among Black and White adults. This study employed dual assessment techniques—ecological momentary assessments (EMA) and ambulatory physiological assessments—to examine the co-occurrence of social interactions and cardiovascular functioning. Multilevel models revealed no racial differences in ambulatory HRV and frequency of friend interactions throughout the day. Findings revealed a between-person link of friend interactions and better HRV in the overall sample. Race-stratified models found a within-person link between friendship interaction and worse HRV and a between-person link between friendship interaction and better HRV for Blacks but not for Whites. Findings suggest friend interactions are more salient for Blacks’ cardiovascular health and may serve as a modifiable factor for preventing cardiovascular diseases.


Background: Pharyngitis is 1 of the most common conditions leading to inappropriate antibiotic prescriptions. When personal protective equipment (PPE) was at first constrained during the COVID-19 pandemic, Intermountain Healthcare recommended limiting rapid group A streptococcal pharyngitis (GAS) testing in urgent-care clinics to preserve PPE. Notably, the percentage of pharyngitis encounters prescribed an antibiotic and that underwent GAS testing is a key Healthcare Effectiveness Data and Information Set (HEDIS) measure. We have described our experience with urgent-care pharyngitis encounters and the impact of temporarily reducing GAS testing on antibiotic prescribing before and during the COVID19 pandemic. Method: We identified all urgent care encounters between July 2018 and August 2021 associated with a primary diagnosis of pharyngitis using ICD-10 CM codes and a validated methodology. Pharyngitis encounters were assessed for antibiotic prescriptions ordered through the electronic health record (EHR) and the use of point-of-care rapid GAS tests. Pharyngitis encounters were analyzed monthly. We assessed the percentage of encounters associated with an antibiotic prescription regardless of testing and the percentage of encounters associated with an antibiotic prescription when a GAS test was or was not performed. We examined 3 periods relating to COVID-19 and GAS testing recommendations: the prepandemic period (July 2018–March 2020), the pandemic onset period (April 2020–June 2020), and the pandemic period (July 2020–August 2021). Results: Prior to the pandemic, the monthly percentage of pharyngitis encounters for which rapid GAS testing was performed was nearly 90% (Fig. Conclusions: Limited PPE in our urgent care centers during the initial months of the COVID-19 pandemic was associated with a mandated substantial decline in rapid GAS testing. As testing volume decreased, we noted a simultaneous relative increase of >30% in antibiotic prescribing for pharyngitis. These findings suggest that rapid streptococcal testing promotes appropriate antibiotic prescribing.Funding: NoneDisclosures: None


Elimination of ventricular tachycardia with epicardial substrate may be limited due to close proximity of the phrenic nerve. In this case report we illustrate the use of a decapolar catheter in a Foley catheter for deviating the prenic nerve to safely perform epicardial ventricular tachycardia ablation. Patients are at high risk for sudden death and ventricular tachyarrhythmias (VT) occur frequently1. Epicardial scar formation is predominantly found at the basal inferolateral left ventricle. Ablation of VTs originating from this area require an epicardial approach, but ablation can be hampered by close proximity of the phrenic nerve (PN)2. Several methods have been described for PN displacement, techniques including fluid overload or vascular or oesophageal balloon inflation3. However, it remains difficult to manoeuvre the balloon pericardially. We present our approach for PN displacement by using a Foley catheter.Pathogenic mutations of the phospholamban (PLN) gene are common in the Netherlands and may give rise to highly arrhythmogenic cardiomyopathiesA 63-year-old male patient with PLN cardiomyopathy (R14del) presented with electrical storm (multiple ICD therapies) despite using amiodarone A. ThrougWe used a Foley catheter to deviate the PN from the ablation site D–E. A deTo our knowledge, this is the first report of the combined use of a decapolar catheter in a Foley catheter for deviating PN to safely perform epicardial VT ablation.


Cerebral infarction due to aneurysm thrombosis in giant intracranial aneurysms is rare (1). Patients with ischemic stroke distal to an unruptured intracranial aneurysm often experience SAH after the stroke and have extremely poor prognosis (2).A 68-year-old man presented with a sudden onset of right hemiparesis and aphasia. Computed tomography (CT) revealed a high-density, round mass in the left middle cerebral artery (MCA) suspected to be an unruptured giant cerebral aneurysm . CT angiNoneTT wrote the first draft and managed all of the submission processes.We have obtained informed consent for this case report.


Teaching Point: Chronic pulmonary schistosomiasis should be suspected in symptomatic patients with an endemic background presenting with migrating pulmonary lesions on high resolution computed tomography scan. A 38-year-old woman with a Sierra Leonean background presented to our institution complaining of pleural pain, fever, and cough. She had a history of human immunodeficiency virus successfully treated with triple therapy and a recent subclinical COVID-19 infection. The patient had not been to Sierra-Leone for 10 years and there was no history of recent travelling or contact with sick patients or Tuberculosis patients.Physical examination was unremarkable. Laboratory tests showed leukocytosis with eosinophilia (0.8 10.E9/l) and high CRP (33.7). Further investigation done with a urinary sample, broncho-alveolar lavage, and serological tests  concluded negative.Figure 1A). No TBC-associated lesions or calcified nodes were observed. The first follow-up HRCT was scanned after seven days  of watchful waiting without any medical therapy. These follow-up images demonstrated a spontaneous regression of some lesions where other nodular lesions demonstrated expansion compared to one week prior. Subsequently the previously described finding of migrating nodular lesions were confirmed on one-month follow-up computed tomography (CT) scan.High resolution CT (HRCT) a few days after admission demonstrated multiple nodular zones of consolidation with surrounding ground glass in the left lower lobe  and treatment was started (Praziquantel) with an interval of two weeks in between doses. On this therapy the patient improved with significant clinical response and a regression of CRP and eosinophilia.Schistosomiasis is a parasitic infection caused by parasitic blood flukes acquired during contact with infested water and is known to be an important cause of disease in sub-Saharan Afrika. It is rarely seen in Europe except for occasional tourism associated exposures.Pulmonary manifestations are most often seen after chronic hepatosplenic involvement with portal hypertension and development of collateral circulation. The eggs of the larvae are subsequently migrating to the alveolar spaces causing an eosinophilic inflammatory response. In this case the predominant HRCT finding of pulmonary involvement was the observation of diffuse nodular opacities which have already been described by Nguyen et al. in 2006 . Our casAn interesting finding in this case is that the patient was recently tested positive for SARS-CoV-2 after having a high-risk contact . It is not clear if COVID-19 infection could trigger a host’s immune response to chronic indolent schistosoma infections or increase the morbidity and mortality of patients who are chronically exposed to the schistosoma parasite.


A 64-year-old male patient with chronic obstructive pulmonary disease presented to our hospital with back pain. Posteroanterior chest radiography findings indicated a calcified, solid nodule having smooth borders and located on the right side, under the diaphragm . Based oEchinococcus granulosus. It is a notable health problem in regions where livestock is still widely dealt withA hydatid cyst is a parasitic disease caused by


Singapore was one of the first countries affected by COVID-19. Measures to contain the spread of COVID-19 include raising the Disease Outbreak Response System Condition (DORSCON) risk assessment to Orange and instituting a movement control order, termed as the Circuit Breaker. These measures have caused significant disruption in primary care and chronic disease management. As the first point of contact in testing suspected cases, primary care providers shifted their focus from non-COVID-19 services. Using an interrupted time series analysis, we examine the associations of DORSON Orange and Circuit Breaker on acute and chronic primary care visits among older adults aged above 50. We found significant reductions in both acute and chronic primary care visits immediately following DORSCON Orange and Circuit Breaker. DORSCON Orange was associated with a drop of 231 mean acute and chronic daily visits (95% CI -356 to -106). Circuit Breaker was associated with a further drop of 268 mean daily visits (95% CI -426 to -111). These reductions were also observed for acute and chronic visits separately. Routine chronic care appointments were deferred or cancelled to reduce the risk of transmission as patients with underlying medical conditions were at higher risk of developing severe complications. Delayed access to primary care can have profound health implications, especially for older adults. Ensuring accessibility to primary care is a key priority in maintaining population health. Understanding the impact of COVID-19 tightening measures on older adults’ primary care utilisation will be useful for future public health planning.


Rational design of therapeutic antibodies can be improved by harnessing the natural sequence diversity of these molecules. Our understanding of the diversity of antibodies has recently been greatly facilitated through the deposition of hundreds of millions of human antibody sequences in next-generation sequencing (NGS) repositories. Contrasting a query therapeutic antibody sequence to naturally observed diversity in similar antibody sequences from NGS can provide a mutational roadmap for antibody engineers designing biotherapeutics. Because of the sheer scale of the antibody NGS datasets, performing queries across them is computationally challenging.http://naturalantibody.com/abdiver), a free portal allowing users to compare their query sequences to those observed in the natural repertoires. AbDiver offers three antibody-specific use-cases: (i) compare a query antibody to positional variability statistics precomputed from multiple independent studies, (ii) retrieve close full variable sequence matches to a query antibody and (iii) retrieve CDR3 or clonotype matches to a query antibody. We applied our system to a set of 742 therapeutic antibodies, demonstrating that for each use-case our system can retrieve relevant results for most sequences. AbDiver facilitates the navigation of vast antibody mutation space for the purpose of rational therapeutic antibody design.To facilitate harnessing antibody NGS data, we developed AbDiver (http://naturalantibody.com/abdiver.AbDiver is freely accessible at Bioinformatics online. Monoclonal antibodies are the largest class of biotherapeutics. Development of successful antibody therapeutics requires selection and engineering of candidate sequences with favorable functional and developability properties. Knowledge of biologically possible mutations at specific positions can be employed to engineer biophysical properties of these molecules . Exploration of natural antibody diversity from NGS datasets relative to a candidate therapeutic would therefore facilitate rapid and effective antibody engineering.The richness of NGS data has implications for rational selection and design; models trained on these data have already shown promise for humanization  or the AIRR Data Commons  (ce (OAS) . We enviV-region profiling service: The AbDiver V-region natural profiling service annotates a query variable-region antibody sequence with the naturally observed amino acid frequency statistics for each position  based indexes for CDRs in full variable-region sequences and CDR3s separately. Variable sequence matches are identified based on the same length CDR1, CDR2 with one residue discrepancy allowed for CDR3. Clonotypes are identified on the basis of the same V-gene and CDR3 sequence identity. The matches are presented using IMGT-based Multiple Sequence Alignment (lignment . Search We created an online portal that facilitates the navigation of natural antibody diversity. We envisage particular application of the service to enable drawing parallels between natural and therapeutic antibodies (Financial Support: none declared.Conflict of Interest: none declared.btac151_Supplementary_DataClick here for additional data file.


Social support networks provide a context within which older adults maintain their safety and well-being. Preparing for disasters and emergency situations can help older adults stay safe independent after a disaster. Self-efficacy to prepare for and handle disaster situations can influence how older adults proactively prepare and protect themselves. Fifty-four older adults 61 to 92 years of age in Eastern Iowa were interviewed before and after participating in an intervention program that helped them develop personalized disaster management plans. Participants reported seven support network members on average, ranging from one to 23. About one-third of the network members were participants’ children and grandchildren, 11% were their siblings and parents, and 58% were non-family members such as friends and neighbors. Out of 549 network members identified, 245 were selected as someone participants can depend on during emergency situations; 47% were family whereas 43% were non-family members. Participants who reported higher numbers of network members whom they can depend on in emergency situations at baseline showed more increase in self-efficacy to manage disasters one-month after receiving the intervention (p=0.02). Having social support network members whom older adults feel they can turn to during emergency situations may help boost their confidence in handling and preparing for disasters through participating in a disaster preparedness program. Participants indeed identified additional members whom they could depend on in disaster situations after the intervention. Future studies may test strategies to enhance social support networks to increase confidence among older adults to prepare for and handle disasters.


Neurofibromatosis type 1 (NF1) is an autosomal-dominant hereditary multi-system disorder that is associated with the development of nervous system tumours. Its incidence is estimated at 1 in 2500 newbornsAccording to the diagnostic criteria for NF1 developed by the National Institutes of HealthPlexiform neurofibromas develop in up to 50% of individuals suffering from NF1. Melanotic neurofibromas are rare tumours representing less than 1% of all neurofibromas.A 27-year-old gravida 2 para 1 Ugandan woman was admitted to the labour ward at 40 weeks of gestation in labour pains. Her first pregnancy reportedly proceeded without increase in size of the cutaneous masses -which were present before the first pregnancy- and ended in successful caesarean delivery of a healthy term baby three years before. She reported progressive increase in cutaneous trunk masses starting from the third trimester of her second pregnancy. Whereas she reportedly lost both parents during her early childhood, she reported no history of neurofibromatosis in her family. On physical examination she was normotensive and presented with café-au-lait macules, axillary freckling, kyphosis and large soft diffuse hyperpigmented plexiform neurofibromas involving the trunk. A clinical diagnosis of NF1 was made. Due to contracted pelvis her child was delivered by caesarean section. Accessing the abdominal cavity required incision of a large suprapubic plexiform neurofibroma, which offered less resistance to incision compared to normal adjacent tissues. The cut surfaces of the neurofibroma exuded with a mixture of blood and clear fluid. A healthy baby was delivered with neither intraoperative nor postoperative maternal complications. One week later, mother and child were discharged. At discharge both the newborn and the then 3-year-old sibling had no dermatological features of NF1. While at home the patient reported rapidly progressing size of cutaneous masses causing difficulty in breathing and inability to walk or lie down .During a home visit 11 weeks after delivery, skin biopsies were obtained from the cutaneous masses. Histopathologic examination revealed neurofibromatous tissue with diffuse infiltrative growth pattern and monomorphic spindle cells with scarce cytoplasm showing positivity for protein S100, confirming the diagnosis of pigmented diffuse type cutaneous neurofibroma without evidence for malignant transformation . ThirteeWe here report on a 27-year-old female who died shortly after her second pregnancy due to the massive progress of giant plexiform neurofibromas. Our case shows similarities to several previous reports of neurofibromatosis-associated maternal complications of pregnancy. Isikoglu et alIn accordance with Leppävirta et alThe simultaneous occurrence of NF1 and pregnancy should warrant close interdisciplinary monitoring of the mother for possible complications. Even when previous pregnancies were not fatally complicated by NF1, subsequent pregnancies can still develop fatal NF1-related complications. In the absence of evidence of malignant transformation, maternal rapid and fatal progression of melanotic NF1 in pregnancy is still a possibility. Pregnancy hormones may influence growth dynamics of neurofibromas. The presence of large plexiform neurofibromas on the abdominal wall should not be an anatomical/surgical limitation of incision for accessing the abdominal cavity.


Several studies have previously documented the development of complications stemming from injection with one of the various COVID-19 vaccines. No study, however, has discussed the spontaneous development of a soft tissue mass shortly after a COVID-19 vaccine injection. We report on 66-year-old female with concerns of a growing shoulder mass, 2 weeks after receiving a COVID-19 vaccine booster. Initial work-up with X-ray and MRI was concerning for a soft tissue neoplasm, specifically a soft tissue sarcoma. Subsequent ultrasound guided biopsy demonstrated a benign granulomatous lesion. No further management was required as the lesion spontaneously resolved during a 3-month follow-up period. It has been previously documented that vaccine components can produce granulomatous inflammation. One study reported postvaccination granulomas in children following the pertussis immunization A 66-year-old female presents to our orthopedic clinic with concerns of a right shoulder rapidly expanding palpable mass. This female with a medical history of rheumatoid arthritis (RA) and rotator cuff surgery presents to our outpatient orthopedic sports medicine clinic concerned about a mildly tender and rapidly enlarging right shoulder soft tissue mass of three weeks duration. She denies systemic symptoms of fever, appetite changes, or weight loss, as well as any antecedent major trauma or other injury. The patient had received the COVID-19 Moderna vaccine booster (3rd dose) in the same deltoid region 4 weeks prior. She notated the injection had been associated with more pain than the prior doses.On physical exam, a nonmobile firm mass was palpable along the superolateral margin of the right deltoid muscle, without overlying skin changes. Neurovascular and motor testing were negative for weakness and sensory deficits. Shoulder radiographs revealed a soft tissue mass in the region of the lateral deltoid, without calcification or underlying osseous involvement . SubsequWe present a case of a 66-year-old woman who developed a localized granulomatous reaction that presented as a mass following a COVID-19 Moderna Booster vaccine Several case reports have documented the development of granulomatous inflammation following vaccine administration. One study reported postvaccination granulomas in children following the pertussis immunization. This same group identified that the ingredient responsible was an aluminum salt adjuvant as 77% of children who developed granulomatous inflammation also developed a contact allergy to aluminum We hereby confirm consent was granted for the publication of this case by the patient, as so long as all records are de-identified.


This observational study compared the outcomes of consumers receiving community-based residential mental health rehabilitation support in Australia under a clinical staffing model and an integrated staffing model where Peer Support Workers are the majority component of the staffing profile. Reliable and clinically significant (RCS) change between admission and discharge in functional and clinical assessment measures were compared for consumers receiving care under the clinical (n = 52) and integrated (n = 93) staffing models. Covariate analyses examined the impact of known confounders on the outcomes of the staffing model groups. No statistically significant differences in RCS improvement were identified between the staffing models. However, logistic regression modelling showed that consumers admitted under the integrated staffing model were more likely to experience reliable improvement in general psychiatric symptoms and social functioning. The findings support the clinical and integrated staffing models achieving at least equivalent outcomes for community-based residential rehabilitation services consumers.The online version contains supplementary material available at 10.1007/s10597-022-01023-8. Contemporary community-based mental health residential rehabilitation services combine medium-to-long term accommodation with intensive rehabilitation and psychosocial support   over 6-to-24-months. Staff support is available 24-h a day.This study considered data from consumers admitted across three CCUs in Queensland over 3-years (12/2014-to-12/2017). One site operated the clinical staffing model, and two operated the integrated staffing model. Under the clinical staffing model, nursing staff reflect most staff roles; there are also senior allied health practitioners and medical staff. Under the integrated staffing model, PSWs reflect the majority team component (> 50%), with a reduction in the number of nursing roles. PSW staff have their own leadership structure and draw on their lived recovery experience to support consumers and guide clinical staff toward recovery-oriented practices. There is no specified interventional framework for PSWs at the CCUs. However, a qualitative study provides a rich description of what PSWs perceived their roles to be, emphasizing self-disclosure and connection through ‘shared engagement in everyday activities… providing authentic opportunities to support residents deal with their experiences and fears… [building] relationships and trust… [and] reducing shame and isolation' (p5) . Ninety-one percent and 89% of eligible clinical and integrated staffing model site consumers consented. Recruitment exceeded the target to achieve > 80% power to detect a 15% difference in the Health of the Nation Outcome Scales (HoNOS)  and subsequent analyses were conducted on measures with > 50% of paired data. Where relevant, scores were transformed so that positive differences reflected improvement on all measures.SDs from the dysfunctional population mean ; [Cut-off 2] Within 2 SDs of the functional population mean ; and [Cut-off 3] Closer to the functional population mean than the dysfunctional population mean.The reliable change index (RCI) was calculated using the Christensen and Mendoza formula  .Reliable and clinically significant (RCS) change was assumed where the change between admission and discharge score exceeded the RCI Analyses were completed in IBM SPSS Statistics Version 27 . Comparability of the three sites was supported by examining measures at admission using the Kruskal–Wallis test . Data from integrated staffing model sites were merged for subsequent analyses.Individual difference scores were categorized as 'reliable improvement ‘or’ no reliable improvement'  based on the RCI. The RCS improvement cut-off producing the largest proportion of improved consumers . Modelling was not undertaken for RCS improvement due to the low event rates. Independent variables (IVs) additional to the ‘Integrated staffing model’ entered in the final models were rationalized based on a threshold of p < 0.200 , MHI Index (64.0%), SFS (55.6%), LSP-16 (51.1%), and HoNOS . No group differences were statistically significant when the stricter RCS improvement criteria were applied.Covariate analyses are detailed in Table This study considered whether consumers receiving TRR support under integrated and clinical staffing models achieve equivalent functional and clinical outcomes at discharge. Regardless of staffing model, most consumers (50.4%-72.5%) showed reliable improvements in negative psychotic symptoms (SANS), psychological wellbeing and distress (MHI-38), social functioning (SFS), disability (LSP-16), and mental health and social functioning (HoNOS). The unadjusted odds of reliable improvement were equivalent between the staffing model groups on all measures, except in general psychiatric symptoms . No significant differences emerged in the likelihood of RCS improvement between the staffing model groups. Covariate analyses suggested that consumers admitted under the integrated staffing model were more likely to experience reliable improvement than in the clinical staffing model on two outcomes (BPRS-18 and SFS). Additional predictors of reliable improvement on the BPRS-18 were having a primary diagnosis of schizophrenia, higher HoNOS total score on admission, and lower levels of education. Additional predictors of reliable improvement in SFS emerging through the covariate analyses were the presence of comorbid substance use, involuntary mental health act status, and lower LSP-16 total scores on admission.The gains in clinical and functional outcomes are consistent with the literature supporting the positive impact of mental health rehabilitation , an outcome highly relevant to the service focus.Reliable improvements in symptoms and functioning generally occurred between admission to and discharge from community-based residential rehabilitation. Furthermore, most consumers demonstrated clinically significant improvements in negative psychotic symptoms and disability. Under the integrated and clinical staffing models, consumers had at least equivalent clinical and functional outcomes. In the context of other emerging research, our findings further emphasise the promising nature of the integrated approach as an alternative to traditional clinical staffing models. More research in other contexts will enhance the ability for future decisions about mental health rehabilitation services staffing to be evidence-informed.Supplementary file1 (PDF 907 KB)Supplementary file2 (PDF 250 KB)Below is the link to the electronic supplementary material.


Correction to: European Radiology10.1007/s00330-022-08895-0The original version of this article, published on 09 June 2022, unfortunately contained a mistake. The sentence "Two different observers performed the measurements; the plain radiographs were analyzed by an orthopedic-trained surgeon with a focus on hip preservation surgery (first author), whereas the computed tomography analysis was performed by a fellowship-trained musculoskeletal radiologist" was corrected to read "Two different observers performed the measurements; the plain radiographs were analyzed by an orthopedic surgery–trained observer with a focus on hip preservation surgery (first author), whereas the computed tomography analysis was performed by a fellowship-trained musculoskeletal radiologist". The original article has been corrected.


Advances in cardiac surgical operative techniques and myocardial protection have dramatically improved outcomes in the past two decades. An unfortunate and unintended consequence is that 80% of the preventable morbidity and mortality following cardiac surgery now originates outside of the operating room. Our hope is that a renewed emphasis on evidence-based best practice and standardized perioperative care will reduce overall morbidity and mortality and improve patient-centric care. The Perioperative Quality Initiative (POQI) and Enhanced Recovery After Surgery–Cardiac Society (ERAS® Cardiac) have identified significant evidence gaps in perioperative medicine related to cardiac surgery, defined as areas in which there is significant controversy about how best to manage patients. These five areas of focus include patient blood management, goal-directed therapy, acute kidney injury, opioid analgesic reduction, and delirium.The online version contains supplementary material available at 10.1186/s13741-022-00250-7. Enhanced Recovery After Surgery (ERAS) programs have become ubiquitous in the field of perioperative medicine and have played a key role in defining the essence of this relatively young discipline. These protocols have typically been applied to non-cardiac surgical populations  and Enhanced Recovery After Surgery–Cardiac Society (ERAS→-Cardiac) organizations are both committed to excellence in perioperative medicine, and in particular for patients undergoing high-risk surgery  to reduce unnecessary transfusions for patients undergoing cardiac surgery  relates to matching therapy with patient demands and avoiding the outstripping of the patient’s reserve throughout their hospital course. Clinical best practice includes quantitative risk assessment  and intensive care unit (ICU)  in the past decade  criteria is neither sensitive nor specific for early identification of AKI. The limitations of serum creatinine and urine output have warranted the development of novel urinary biomarkers that have shown predictive value. Biomarkers allow the diagnosis of kidney injury to be made earlier, even in the absence of concurrent or subsequent kidney dysfunction  in perioperative cardiac medicine. There are implications for resource utilization as well as clinical outcome improvements in the five clinical topics and research questions (see Additional file Additional file 1. Research Questions.


A 49-year-old woman developed thunderclap headaches triggered by straining during defecation. Magnetic resonance imaging (MRI) on day 3 after the onset revealed somewhat poor delineation of the bilateral distal posterior cerebral arteries without cerebral parenchymal lesions, which suggested possible vasoconstriction  and 1B. (1). Vasoconstriction has been reported to start at distal vessels and migrate more proximally to larger vessels (2). Therefore, serial MRI examinations are important for diagnosing RCVS.In RCVS, vasoconstriction can be difficult to detect in very distal branches, which can make its diagnosis challenging NoneAll authors contributed to patient care. Tetsuya Hashimoto wrote the manuscript and the other authors revised it.This study did not require IRB approval.Written informed consent was obtained from the patient to publish.


Prior literature has indicated low socioeconomic status (SES) and regional differences as epidemiological risk factors for disability pension (DP) due to mental disorders.Our studies aimed to examine these associations and differences in greater detail, with separate consideration of the risk factors for mood disorders (F30–39) and non-affective psychotic disorder (F20–29) DP.Subjects (N = 36 879) were all those granted DP due to a mental disorder for the first time between 2010 and 2015 in Finland. All the subjects were matched with three controls. Education, income and occupational status were used as measures of SES. Conditional logistic regression models were used to study SES differences. Negative binomial regression analysis was used to study the levels of DP risk in the Finnish hospital districts.DP recipients had low educational and income levels and often lived alone. The risk of DP was greater in white-collar occupational groups compared with blue-collar workers. Students had the greatest risk of DP for all mental and mood disorders. Significant differences in the regional mental disorder DP risks did not appear to follow the traditional Finnish health differences.We found evidence of SES factors and regional variation associating with mental disorder-related severe loss of working and studying ability in a disorder-specific way. The increased risk of white-collar worker DP could be related to the psychosocially demanding contemporary working life. Regional variation in DP may at least partly relate to differences in regional mental health service systems.No significant relationships.