Primary cutaneous B-cell lymphomas (PCBCLs) are uncommon diseases with heterogeneous clinical pictures and prognoses. PCBCLs are classified into 3 main subtypes: cutaneous marginal zone lymphoma (PCMZL), cutaneous follicle center lymphoma (PCFCL), and cutaneous diffuse large B-cell lymphoma, leg-type (DLBCL-LT). Each subtype has a distinct clinical presentation and histopathological, molecular and immunologic profiles. They also differ considerably in prognosis and treatment . We repoA 32-year-old woman presented with multiple tender erythematous papules of 1 month’s duration on her right forearm on top of an AV fistula that was made for renal dialysis. She was a known renal failure patient since her early twenties and had been on renal dialysis since then. She reported that lesions on her forearm were increasing in number and size and becoming more painful. Physical examination revealed multiple erythematous papules and nodules on the forearm. They were firm in consistency and tender on palpation. One of the nodules showed superficial ulceration . Given tHistopathological examination revealed grenz zone and diffuse infiltration of large pleomorphic cells occupying the whole dermis . Some miPCBCL-LT is considered an aggressive type of cutaneous B-cell lymphoma. It presents clinically as nodules of violaceous color with frequent ulceration. It is predominant in elderly females. Secondary involvement of other organs can occur shortly after diagnosis that leads to a poor prognosis. Distinction for systemic lymphoma can be difficult . TypicalPrimary cutaneous B-cell lymphomas are rare tumors and often represent a diagnostic challenge. Extensive immunohistochemical studies are crucial to determining the type in addition to laboratory and radiological workups to exclude extracutaneous involvement.


The management of cardiac arrest during video assisted thoracic surgery is challenging. Checklist use improve the management of operating-room crises.Case presentation: Cardiac arrest (asystole) occurred during anatomical pulmonary resection by minimally invasive surgery. Conversion to thoracotomy was decided (thoracic surgeon and anesthesiologist conjointly) to check for absence of cardiac bleeding and to start cardiac massage (4 min no-flow). After few minutes, ventricular fibrillation occurred and persisted despite shocks. Extracorporeal life support with veno-arterial extracorporeal membrane oxygenation allowed a return of spontaneous circulation (45 min low-flow).The patient survived without central neurologic deficit due to perfect team work process using a crisis check-list (strengthened by a comprehensive simulation program with crisis resource management). A multicenter series showed a prevalence of 1.5% of major intraoperative complications after video assisted thoracic surgery (VATS) anatomical lung resections . The aimA 56-year-old man had smoking history at 40 packs / year, no other history. A suspicious pulmonary nodule was detected in the left lower lobe. FEV1 and DLCO values were respectively 93 and 55%. A basal segmentectomy was planned for this increasingly central nodule according to multidisciplinary meeting.VATS segmentectomy was started according to the World Health Organisation surgical safety checklist. Cardiac arrest (asystole) occurred immediately after placement of the first port . After communication between the thoracic surgeon and anesthesiologist, it was decided to apply the Code Red procedure Fig. , to convIn post-operative, coronarography showed coronary disease, without stenting. Then, redo for pericardial hemostasis was done by thoracotomy during the night. Therapeutic hypothermia (36 degrees Celsius) was done over a period of 24 h. The patient was weaned off the pump at Day 2 because of cardiac recovery, then extubated at Day 4 without central neurologic deficit. He was discharged from intensive care unit at Day 7. The left ventricular ejection fraction was 45%. The patient was discharged from hospital at Day 18. Another coronarography with interventricular artery stenting was done at 2 months.In prolonged cardiac arrest with failing conventional measures, rescue by extracorporeal support provides an ultimate therapeutic option . VA ECMOAn in situ intraoperative crisis simulation model for thoracic surgical emergencies was created, implemented, and demonstrated to be effective as a proof of concept at identifying latent threats to patient safety and differentiating the nontechnical skills of trainees and consultant surgeons . We haveOur perfect team work process was strengthened by a comprehensive simulation program focussing on human factors and surgical crisis resource management. Our intraoperative crisis simulation program allowed us to apply perfectly our Code Red for the management of cardiac arrest during minimally invasive thoracic surgery.


Haemophilus influenzae (NTHi) is an important cause of human illness, including pneumonia and acute exacerbations of chronic obstructive pulmonary disease (COPD). We report here the draft genome of an isolate of NTHi collected from the sputum of a patient presenting with COPD in Tasmania, Australia.Nontypeable  Haemophilus influenzae (NTHi) is an important cause of human illness, including pneumonia and acute exacerbations of chronic obstructive pulmonary disease (COPD). We report here the draft genome of an isolate of NTHi collected from the sputum of a patient presenting with COPD in Tasmania, Australia.Nontypeable  Haemophilus influenzae (NTHi) is a key pathogen that colonizes damaged airways in COPD patients and causes acute exacerbations that contribute to morbidity and mortality (–Chronic obstructive pulmonary disease (COPD) is a serious, progressive condition characterized by a persistent reduction in lung airflow . It has ortality –7. Here,2 atmosphere followed by storage at 2 to 8°C. Bacterial identification was performed using a Bruker matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometer. A single colony of Haemophilus influenzae was suspended in 200 μl phosphate-buffered saline (PBS), and then genomic DNA was extracted using the DNeasy blood and tissue kit . The genomic DNA preparation was further purified using the High Pure PCR template preparation kit . DNA library preparation was carried out using a Nextera XT DNA library preparation kit  as described previously  website (https://pubmlst.org/hinfluenzae/) (–uenzae/) , assigneuenzae/) –17, whicIn conclusion, this study presents the published genome sequence assembly of an NTHi isolate from a case of COPD in Tasmania. The application of genome sequencing has the potential to provide insights into recurrent exacerbations of COPD due to NTHi and the ability to distinguish between relapse and reinfection.This work was conducted in accordance with ethics approval number H0016214 from the Tasmanian Health and Medical Human Research Ethics Committee.JAAECN000000000. The version described in this paper is version JAAECN010000000. The associated BioProject and BioSample accession numbers are PRJNA603840 and SAMN13942196, respectively.This whole-genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number


A 69-year-old woman with hyperlipidemia and ocular cicatricial pemphigoid presented with frequent (burden: 47%) symptomatic  premature ventricular complexes (PVCs) with an outflow tract morphology and associated cardiomyopathy [left ventricular (LV) ejection fraction: 40%]. She underwent a negative ischemic workup and was started on guidelines-directed medical therapy without improvement in her LV function.She underwent an initial PVC ablation using activation mapping with an ablation catheter and radiofrequency (RF) energy was delivered from the right ventricular outflow tract (RVOT), LV outflow tract (LVOT), and right–left coronary commissure. Unfortunately, the PVC recurred three months later and her cardiomyopathy continued.. Activation mapping was then performed in the coronary sinus at the level of the anterior interventricular vein with an ablation catheter. Early far-field timing was also noted in this location.She presented for a redo ablation with the Advisor™ HD Grid Mapping Catheter, Sensor Enabled™. Initial activation mapping in the RVOT revealed late timing as was the case in the coronary cusps. Meanwhile, activation mapping with the Advisor™ HD Grid catheter in the LVOT revealed an early fractionated signal just below the left coronary cusp .A coronary angiogram revealed the ablation catheter to be at a safe distance from the left anterior descending coronary artery. Ablation was performed in this region at 20 W with suppression of the PVC achieved after 15 seconds, but it returned after 30 seconds. Attention was then turned to the early signal in the LVOT identified with the Advisor™ HD Grid catheter. Ablation at this site with 35 W eliminated the PVC within five seconds At five months postablation, the patient remained without any further PVCs and with normalization of her LV function. Guidelines-directed medical therapy is gradually being weaned. This case demonstrates the greater value of high-resolution signal detection with the Advisor™ HD Grid catheter in the case of intramural PVCs relative to traditional ablator-based mapping.


As the novel coronavirus 2019 (COVID-19) has rapidly become a global pandemic, emergency physicians worldwide play essential roles in the frontline management of critically ill patients with COVID-19. In emergency airway management, video laryngoscopes (VL) are recommended over direct laryngoscopy to minimize healthcare worker exposure to aerosolized particles.2Emphasis should be on proper training with the DIY VL, as intubation with VL requires different skills when compared with DL and commercial VL.In conclusion, we believe DIY VL is an acceptable option in clinical settings with limited resources in response to emergency endotracheal intubation in the COVID-19 pandemic.VideoThe video shows a view from the low-cost videolaryngoscope during simulated intubation. Please see Supplementary File.


Anastomotic leak remains a common complication after esophagectomy. It is associated with perioperative mortality and prolonged hospital stay. Some have suggested that it may also contribute towards poorer long-term survival, although the mechanism is unclear. A French multicenter study defined severe esophageal leak (SEAL) as that which equated to a grade III/IV Clavien–Dindo complication. This study demonstrated a poorer long-term prognosis in patients who developed SEAL following esophagectomy;The present study evaluates outcomes from a single center over a 20-year period.These data may help allay fears that anastomotic leak may potentially contribute towards poorer overall prognosis. The importance of managing leaks appropriately is vital for short-term outcomes. High-volume centers, by definition, have increased experience in managing such complications, and a judicious and aggressive strategy has been shown to lead to minimal risk of perioperative mortality from such leaks.


Calorie restriction (CR) is a promising strategy to attenuate age-related disease risk. Higher protein diets enhance satiety but may also impair metabolic health and accelerate aging. The effect of higher protein intake on adherence to CR and cardiometabolic markers of healthspan remains unknown. We used the Geometric Framework for Nutrition to examine the association between diet composition and 1) CR adherence; and 2) cardiometabolic risk factors during a 2-year intervention. The CR group consumed higher percentage energy from protein and lower fat at 12 months compared to baseline . Higher protein intake over the 2-year intervention was associated with higher adherence to CR. No effect of diet composition on cardiometabolic risk factors was observed. These findings suggest that dietary protein plays a critical role in adherence to CR with no adverse effects on cardiometabolic markers of healthspan. Part of a symposium sponsored by the Nutrition Interest Group.


A 69-year-old lady diagnosed with congestive cardiac failure three years prior presented with worsening shortness of breath and bilateral leg swelling. She does not have a history of acute coronary syndrome, however an angiogram performed two years ago revealed a two-vessel disease. She also has hypothyroidism secondary to thyroidectomy. A cardiovascular examination revealed a raised jugular venous pulsation, displaced apex beat, muffled heart sounds, a pan systolic murmur heard loudest at the mitral region with radiation to the axilla and mid inspiratory crepitations over the lung bases with pitting oedema till the level of the mid-shin. These features are suggestive of an acute decompensation of congestive cardiac failure with mitral regurgitation. Her previous echocardiogram revealed an ejection fraction of 28% with global hypokinesia, dilated left ventricle and severe mitral regurgitation. A chest radiograph was done and revealed a very massive symmetrical cardio pericardial silhouette. This heart has a globular appearance, a flask or water bottle configuration with relatively smooth left and right cardiac contours. This is characteristic of pericardial effusion. The patient was treated with intravenous diuretics and supplemental oxygen along with the necessary supportive treatment of cardiac failure.


The concentration determination of such xenon binding sites in samples of unknown dilution remains, however, challenging. Contrary to 1H CEST agents, an internal reference of a certain host  at micromolar concentration is already sufficient to resolve the entire exchange kinetics information, including an unknown host concentration and the xenon spin exchange rate. Fast echo planar imaging (EPI)-based Hyper-CEST MRI in combination with Bloch–McConnell analysis thus allows quantitative insights to compare the performance of different emerging ultra-sensitive MRI reporters.Xenon magnetic resonance imaging (MRI) provides excellent sensitivity through the combination of spin hyperpolarization and chemical exchange saturation transfer (CEST). To this end, molecular hosts such as cryptophane-A or cucurbit[ It lacks a “bulk pool” that is in chemical exchange with a dilute agent pool that can indirectly provide enhanced sensitivity by accumulating a signal loss from the CEST agent. The hyperpolarizable noble gas 129Xe, however, has been used with CEST detection in an approach coined Hyper-CEST because it only engages in transient, non-covalent binding . We demonstrate in this study that a careful analysis of saturation transfer spectra acquired with a set of different RF saturation pulse settings allows determination of all these parameters by using the full Hyper-CEST (FHC) solution ) = tot]/[Xe]) as given in    are conso 150 μM . This isgiven in . We can [Xe] see . This yi ± 2) μM . This wafB in this case thus requires at least [CrA-ma]min ≈ 1 129Xe NMR spectroscopy. The important prerequisite for the absolute quantification method proposed in this present work is that both the Xe host occupancy When multiple samples with different host concentrations are under investigation, the saturation pulse strengths should be chosen accordingly. This ensures that the CEST effect responses remain within a reasonable dynamic range of the Xe depolarization rate . Furtherz-spectra is the experimental confirmation that a reproducible steady-state magnetization has been reached after each gas delivery for the individual acquisitions. Another aspect to consider is a variable protonation at the host portals that might impact the Xe affinity in different pH. While the concept of pH is irrelevant in the DMSO conditions used here, such pH-depending protonation might be a relevant aspect in aqueous solutions and should be adjusted with appropriate buffer systems for comparison studies.This condition can be easily fulfilled in in vitro experiments where the repetitive bubbling with the Xe gas mix ensures that the solution is always chemically saturated with the gas according to the Ostwald coefficient. The fraction of bound Xe is determined by the binding constant and remains unchanged during the experiment. A stable baseline in the Overall, this exchange parameter mapping technique is (for now) only reliable and attractive for in vitro applications where different hosts for reversible binding of Xe shall be compared side by side with two clearly defined spin pools. Chemical engineering that aims to tune the exchange rate is a prime example of this. Translation to biological systems requires more detailed separation of the individual components as a live cell assay would clearly increase the number of involved spin pools (Xe and host can both be present in different micro-environments). In vivo applications would also be limited until there is further knowledge available regarding the complete exchange network of all participating pools, the occupancy of hosts, and the solubility of Xe and how this can be compared in different tissues and if any correction methods can be applied to obtain absolute quantitative numbers.It is noteworthy that a quantification based on this approach requires a spectrally resolved CEST-response because the math framework otherwise fails to derive the exchange kinetics. Therefore, hosts providing exchange kinetics that appear fast on the NMR timescale and only cause a broad MT effect  cannot 129Xe in CEST studies has certain advantages over exchanging 1H nuclei: First, it allows combination with spin hyperpolarization  = 50 129Xe  was obtained with a continuous-flow (0.35 SLM) custom-designed polarizer  = 2340 Circa 25 % Xe spin hyperpolarization of a 2% Xe gas mix {2, 10, 88}-vol.% of {Xe, Nolarizer  via spinT = 295 K). For excitation and detection, a 10 mm inner diameter double-resonant probe (129Xe and 1H) was used. The 129Xe Hyper-CEST images were obtained with a 129Xe Hyper-CEST echo-planar imaging [k-space sampling where only 32/1.68 = 19 lines of the full k-space have been acquired [NMR experiments were done at shown in , such in imaging  pulse seacquired ); doubleacquired ); echo tz-spectra from different saturation parameters (see figure captions). A mask was applied to exclude pixels outside the phantom area. All calculations and fitting routines were implemented and performed in Matlab 7  on a standard desktop PC  as described in [qHyper-CEST analysis was performed based on the imaging series that yielded pixel-wise ribed in . Pixel-wBy extending the qHyper-CEST concept to imaging with pixel-wise analysis, we mapped the unique fingerprint of a specific Xe-host system within a particular chemical environment. We could demonstrate the determination of absolute host concentrations as an extended analysis of the previously introduced FHC approach. Our results provide faster insights into the Xe-host binding kinetics since multiple Xe-host systems can be screened at once.This quantitative MRI approach demonstrates the potential of the FHC approach for data sets with increased spatial resolution compared to initial qHyper-CEST analysis. It will be of particular interest for in vitro tests of newly developed Xe biosensors but also for quantitative physical chemistry studies of Xe-binding host structures where the simultaneous detection of multiple samples overcomes the challenges of introducing hyperpolarized spin reporters.


Psychotropics use to manage behavioral and psychological symptoms of dementia (BPSD) in nursing homes (NHs) has been the focus of policy attention due to their adverse effects. We hypothesized that NHs with lower nursing staffing would have greater reliance on psychotropics use to control BPSD. A NH deficiency of care can be cited for inappropriate psychotropics use (F-tag 758). The association between the occurrence of F-758 tags and nurse staffing in residents with dementia was examined using the 2017-18 Certification and Survey Provider Enhanced Reporting data . Staffing measures included nursing hours per resident day (HPRD) and registered nurse (RN) skill-mix. Generalized linear mixed models that included covariates  estimated the magnitude of the associations. There were 1,872 NHs with F-758 tags indicating inappropriate psychotropics use for NH residents with dementia. NHs with greater RN and certified nurse assistant (CNA) HPRD had significantly lower odds of F-758 tags  and similar findings were found in NHs with greater RN skill-mix . There were no significant associations between the occurrence of F-758 tags and licensed practice nurse and unlicensed nurse aide HPRD. This study found that RN and CNA staffing had inverse associations with inappropriate psychotropic use citations among residents with dementia. NHs with higher RN staffing ratios may be better able to implement alternatives to pharmacological approaches for BPSD. It is suggested that NHs be equipped with adequate nurse staffing levels to reduce unnecessary psychotropics use.


The treatment strategy for aortic valve and lung cancer patients includes concomitant or two-stage procedures. Conventional simultaneous operations are usually performed under the median sternotomy.A 72-year-old man was admitted to our hospital after experiencing chest tightness after activity for two months. Aortic valve regurgitation had been confirmed when squamous cell carcinoma of the lung was discovered. The therapeutic strategy for these patients is controversial. Considering the potential risk of tumour metastasis and the risk of cardiopulmonary bypass (CPB), we recommended concomitant transcatheter aortic valve implantation (TAVI) and a lobectomy. A trans-apical TAVI with left-sided intercostal thoracotomy was successfully performed, followed by an immediate video-assisted thoracoscopic surgery (VATS) lobectomy and selective lymph node dissection.We suggest that a one-stage surgery of pulmonary resection following TAVI is an acceptable and safe choice after careful evaluation and should be performed as soon as possible in response to lung cancer in elderly patients with aortic valve disease. Lung cancer can be incidentally discovered during preoperative evaluation of aortic valve regurgitation. The treatment strategy includes concomitant or two-stage surgery. The conventional simultaneous operation for valve replacement and lung resection is usually performed under the median sternotomy. Here, we describe a way to treat both diseases through concomitant trans-apical TAVI and VATS lobectomy and selective lymph node dissection, avoiding the adverse effects of CPB, repeated anaesthesia and pain without delaying lung cancer treatment.A 72-year-old male patient was admitted to our hospital. He had been experiencing chest tightness and blood in his sputum for two months. A transoesophageal ultrasound revealed moderate to severe aortic valve regurgitation Fig. a, a resuLung cancer and severe valvular heart disease occasionally coexist. The therapeutic strategy for these patients is controversial. The incidental finding rate of lung nodules on CT scans for TAVI is about 18% , and a fThe number of elderly patients with simultaneous aortic valve disease and lung tumours is increasing. We suggest that a one-stage surgery of pulmonary resection following TAVI is an acceptable and safe choice after careful evaluation and should be performed as soon as possible for elderly patients with lung cancer and aortic valve disease.


Ablation at this region terminated the AFL within a few seconds and the AFL was no longer inducible postablation. This case demonstrates the use of the high-resolution Advisor™ HD Grid catheter using high-density wave technology to analyze orthogonal electrograms at a single location, thereby facilitating rapid identification and treatment of AFL.A 75-year-old woman with hypertension and symptomatic drug-refractory paroxysmal atrial fibrillation (AF) elected to undergo AF ablation. Pulmonary vein isolation was performed with a wide antral circumferential ablation. As her esophagus was bordering the left-sided ostia and our left-sided ablation lesion set was more antral, we were also able to isolate her posterior wall. Rapid atrial pacing postablation induced an eccentric atrial flutter (AFL) with a cycle length of 260 ms. Activation mapping with the EnSite Precision™ mapping system with the Advisor™ HD Grid Mapping Catheter, Sensor Enabled™ catheter revealed localized reentry at the left atrial appendage/left superior pulmonary vein ridge. At the critical location, significant compression was seen on the activation color map with a fractionated signal with a duration of 190 ms, essentially encompassing two-thirds of the tachycardia cycle length


An 18 yr old caucasian man presented with neurological symptoms and breathlessness. Echocardiography demonstrated a left ventricular abnormality of unclear aetiology. The patient was referred onwards to our unit for further assessment by cardiac magnetic resonance. Imaging was performed on a 1.5 T Philips Intera Acheiva, using a five element phased-array surface coil.On steady state free precession (SSFP) cine images the appearances were of marked left ventricular hypertrophy with partial cavity obliteration. Left ventricular cavity volumes were reduced and ejection fraction was 54%. Early post contrast inversion recovery gradient echo (IRGE) images showed an area of low signal within the LV cavity distinct from the myocardium. The mass was markedly hypointense to both myocardium and the blood pool. Delayed IRGE sequences 10 minutes following the administration of contrast demonstrated widespread subendocardial hyperenhancement in all myocardial segments sparing only the basal septum. CMR was able to confidently establish the diagnosis of endomyocardial fibrosis with a large left ventricular thrombus burden.The patient had no history of foreign travel or malnutrition, making a vasculitis the most likely aetiology.Baseline blood testing demonstrated a mild eosinophilia of 17%, a C reactive protein of 27 mg/L  and an erythrocyte sedimentation rate of 27 mm/h . Further imaging demonstrated normal renal arteries on MR angiogram. However CT thorax demonstrated pulmonary haemorrhage and MRI brain demonstrated white matter abnormalities in the cerebral cortex. These findings were in keeping with the clinical diagnosis of vasculitis, Although autoantibodies were all normal, the most likely process is a variant of Churg Strauss.Cardiac MR was able to establish the diagnosis of endomyocardial fibrosis which was pivotal in identifying the underlying vasculitic disease process.


Our type system addresses this difficulty with a novel combination of refinement types and fractional ownership types. Fractional ownership types provide flow-sensitive and precise aliasing information for reference variables. ConSORT interprets this ownership information to soundly handle strong updates of potentially aliased references. We have proved ConSORT sound and implemented a prototype, fully automated inference tool. We evaluated our tool and found it verifies non-trivial programs including data structure implementations.We present ConSORT, a type system for safety verification in the presence of mutability and aliasing. Mutability requires


The shotgun injury may cause large-scale bone and soft tissue destruction especially when people get shot from a very close range. Here we present a case of Gustilo type IIIC open fractures of the proximal tibia with vascular injury, large bone and soft tissue defect treated with Masquelet technique in combination with cross-leg pedicle flap.A 34-year-old man presented with open proximal tibial fracture of Gustilo type IIIC, AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification 41-C2.3, caused by a shotgun injury from very close range (2 m). The wound was complicated with anterior tibial artery injury and segmental bone loss. After radical debridement, the fracture was temporarily stabilized with external fixator, followed by double plate fixation with cement spacer filled into the bone defect in accordance with the Masquelet technique. The soft tissue defect was covered with a cross-leg pedicle flap. At 3 months after trauma, the cement spacer was replaced by mixed autologous and synthetic bone graft. The fracture had successfully healed by 12 months after trauma.When the integrity of lower leg vessels is doubtful, the Masquelet technique in combination with cross-leg pedicle flap is an effective and safe alternative treatment for this condition.We recommend to manage Gustilo type IIIC open fractures of the proximal tibia with bone defect with Masquelet technique in combination with cross-leg pedicle flap especially when the free flap technique is relatively contraindicated or trauma surgeon is not a highly-skilled microsurgeon. TradiVery few studies have reported clinical and radiographic outcomes of Gustilo type IIIC open fractures caused by shotgun injury . Here we2The case report has been written according to the SCARE 2018 guidelines .2 open wound. Radiographs indicated comminuted fracture with bone loss about 7 cm and multiple shotgun pellets . We filled the bone defect with vancomycin and gentamicin loaded cement spacer . The skiWe replaced the cement spacer with mixed autogenous and synthetic bone graft at 12 weeks after trauma ,6. At 123The treatment of open fracture involves segmental bone loss and large soft tissue defect along with major vessel injury caused by shotgun injury is challenging. Free vascularized osteocutaneous flap such as fibula and iliac crest flap have been reported as reliable flap with satisfactory results . HoweverBone transport is also an effective technique for long bone defects. However, the prolonged external fixator use may cause stiffness of ankle and knee, low quality of life and potential pin tract infection are also the drawbacks.Generally, nonvascularized bone graft is not advocated for reconstruction in bone defects over 5 cm. Masquelet et al. introduced a technique to treat bone defects of more than 5 cm with non-vascularised bone graft in 2000 . The incMasquelet introduced a technique to treat segmental bone loss . ProponeThe cross-leg pedicle flap is a historical flap for treating lower extremity trauma . When fr4This case report highlights the value of treating segmental bone loss, large soft tissue defect and vascular injury caused by shotgun injury using the Masquelet technique in combination with cross-leg pedicle flap coverage. We recommend this effective and safe method to restore bone and soft tissue defect simultaneously without the need for microsurgery while ensuring an excellent outcome.All the three authors disclose any financial and personal relationships with other people or organisations that could inappropriately influence of our work.We have no source of funding for our research.We have the IRB approve letter attached as supplement data.We have consents from the patient and authors.Chun-Yen Chen’s work was Data collection, and original draft.Yung- Cheng Chiu’s work was study design and methodology providing.Cheng-En Hsu’s work was data analysis or interpretation and writing the paper.Out was not a human study.Yung- Cheng Chiu AND Cheng-En Hsu.Not commissioned, externally peer-reviewed.


We study two models: a pessimistic model where flows interfere in a worst-case manner along equal-cost shortest paths, and an optimistic model where flows are routed in a best-case manner, and we present a complete picture of the algorithmic complexities. We further propose a strategic search algorithm that checks only the critical failure scenarios while still providing correctness guarantees. Our experimental evaluation on a benchmark of Internet and datacenter topologies confirms an improved performance of our strategic search by several orders of magnitude.To ensure a high availability, communication networks provide resilient routing mechanisms that quickly change routes upon failures. However, a fundamental algorithmic question underlying such mechanisms is hardly understood: how to verify whether a given network reroutes flows along


Kidney stones (KS) versus Nephrocalcinosis (NC) all arrows pointed upwards to indicate an increase.The original publication of this article  containeKidney stones (KS) versus Nephrocalcinosis should point downwards to indicate a decrease. The exception is Urinary proteins, this remains an increase.However, as shown in the data from the tables: all arrows in The incorrect Fig.  and corr


After carotid artery stenting, retrieval of the embolic protection device can sometimes be difficult due to incomplete stent expansion, stent fracture, vasospasm, and vessel tortuosity. In this technical report, we describe a novel rescue technique used in a patient with diffuse calcific atherosclerosis of the left common and proximal left internal carotid arteries who underwent left internal carotid artery stenting with cerebral protection and in whom, due to an under-expanded proximal carotid stent strut in relation to a densely calcified plaque, we were initially unable to advance the retrieval device. Carotid artery stenting is the preferred treatment for patients with symptomatic carotid stenosis and who are considered “high risk” for carotid endarterectomy . The useA middle-aged patient presented to our clinic with a past medical history of multiple prior strokes, hypertension, hyperlipidemia, chronic kidney disease, and chronic obstructive pulmonary disease (COPD). The patient developed stroke symptoms while in rehabilitation for a fractured hip after a fall. On work-up, the patient was found to have extensive atherosclerotic changes throughout the cervical vasculature, including bilateral severe to critical internal carotid artery (ICA) stenoses, right vertebral artery occlusion and moderate stenosis of the left vertebral artery origin Figure  and 1B. The patient underwent right carotid endarterectomy but unfortunately developed hoarseness postoperatively due to vocal cord palsy. The patient also had a preexisting type two aortic dissection. For the treatment of her high-grade left internal carotid artery (ICA) stenosis, she opted for minimally invasive endovascular stenting. The procedure was performed under monitored anesthesia care (MAC) using dexmedetomidine (Precedex™) with continuous cardiovascular monitoring. A 65 cm long 6 French Super Arrow-Flex® sheath  was placed in the proximal descending aorta and a 6 French Envoy® guiding catheter  was used to select the origin of the left common carotid artery (CCA). There was a severe diffuse atherosclerotic disease of the left CCA and ICA with extensive irregular atherosclerotic plaque formation and multiple plaque ulcers Figure . Two areAn 8 x 36 mm Carotid Wallstent® (Boston Scientific) was then deployed in the left cervical ICA, spanning from the C3 to C7 level and extending into the left CCA Figure . Due to Despite successful angioplasty, the capture device for the EPD would not advance over the wire. We then advanced a 125 cm soft-tipped 5 French Sofia® intermediate/distal access catheter (MicroVention® Terumo) Figure , arrow aTwo 8 x 29 mm overlapping Carotid Wallstents (Boston Scientific) were then placed across the severely diseased left CCA Figure -C up to There have been descriptions of rescue strategies to retrieve trapped embolic protection filters including external carotid compression, rotation of the head to the contralateral side to change carotid angulation, use of different catheters like the vertebral and JR-four catheters and carotid endarterectomy (CEA) -8. CEA fHaving a "plan B" can make all the difference between a successful and unsuccessful procedural outcome. The navigability of a distal access catheter makes it a useful tool not only for intracranial interventions but also as a rescue tool to recapture a trapped EPD. Our rescue technique has not been described in the literature and could prove very useful in difficult situations during carotid artery stenting. Other helpful considerations include the use of docking wires which provide extra length to EPD wires and the "buddy-wire" technique which can help provide stability and guidance for a catheter.


We report a 62-year-old woman who was scheduled for an elective Tirone David valve sparing aortic root replacement under cardiopulmonary bypass. Within the next few hours, the patient developed bilateral acute ischemia of both lower limbs. A thoracic and abdominopelvic computed tomography scan showed acute Type A aortic dissection with a perforation at the brachiocephalic arterial trunk and a complete malperfusion of the inferior mesenteric and iliac arteries. Iatrogenic acute Type A aortic dissection (AAAD) following cardiopulmonary bypass may occur intraoperatively (with recognition during the primary cardiac surgery), within the first 2 weeks, classified as early postoperative AAAD or late (>30 days after primary heart surgery).We report the case of a 62-year-old woman without previous medical history. After discovery of an aortic murmur, echocardiography demonstrated 3+ aortic insufficiency and an aneurysm of the ascending aorta. Computed tomography (CT) scan revealed an ascending aortic diameter of 70 mm.The patient underwent an elective David valve sparing aortic root replacement.Within the next few hours, the patient developed bilateral acute ischemia of both lower limbs and asymmetric blood pressure in the upper limbs. Transthoracic and transesophageal echocardiography revealed a flap in the distal ascending aorta, the aortic arch, and the descending thoracic aorta, suggestive of acute aortic dissection. A thoracic and abdominopelvic CT scan with three-dimensional volume rendering was performed. It showed an acute Type A aortic dissection with fenestration at the brachiocephalic arterial trunk and complete malperfusion of the inferior mesenteric and iliac arteries 23.Despite maximal management with revascularization of the lower extremities by axillofemoral bypass, total colectomy, and stenting of the abdominal aorta, evolution was unfavorable with multiorgan failure leading to the death of the patient 72 hours later. Iatrogenic AAAD is a rare complication that must be recognized early to deliver the appropriate therapy. Intraoperative diagnosis may be difficult.


Multifocal choroiditis (MFC) is a relatively uncommon bilateral inflammatory chorioretinopathy affecting Caucasian young women with myopia. We present images from a case of completely unilateral multifocal choroiditis following EBV-positive mononucleosis that demonstrated a dramatic clinical response to immunosuppression.A 20-year-old woman with bilateral high myopia (−6D) and a documented normal prior retinal examination presented with visual loss in the right eye 2 months following confirmed Epstein-Barr virus (EBV) positive mononucleosis. Ophthalmoscopic examination showed completely unilateral placoid lesions of variable age. The left eye was unaffected. Fluorescein angiography revealed active leakage, especially in the parafovea. Spectral domain optical coherence tomography (SD-OCT) demonstrated sub-retinal pigment epithelial nodular deposits, some of which were confluent with overlying intra-retinal fluid and indistinct margins. Upon treatment with the immunosuppressant azathioprine there was significant resolution of the lesions in her right eye along with improvement in vision.This is a rare case of completely unilateral MFC following an episode of EBV positive mononucleosis that showed a dramatic response to immunosuppression. MFC is a relatively uncommon, chronic, bilateral inflammatory chorioretinopathy that predominantly affects young healthy myopic white women between the second and sixth decades of life with no known associated systemic disease or other recognized ocular syndromes . It is cA 20-year-old woman presented with visual loss in the right eye. She had high myopia bilaterally (−6D). A normal prior retinal examination was documented 5 years prior to presentation. A routine contact lens exam 1 year prior to presentation recorded 20/20 vision. Review of systems was notable for confirmed EBV positive mononucleosis 2 months prior to the development of ocular symptoms. At that time, she had headaches, fatigue, sore throat and lymphadenopathy. No eye pain, redness or light sensitivity was noted. EBV mononucleosis was confirmed using the heterophile antibody (Monospot) test. The patient reported trouble with distance vision 2 months after the mononucleosis was diagnosed.At presentation 6 months after her symptoms began ophthalmic examination of the right eye revealed quiet anterior chambers with scant anterior vitreous cells only in the right eye. Retinal examination showed punched out nummular chorioretinal lesions admixed with patchy areas of coarse pigmentation overlying subretinal fibrosis. The completely unilateral placoid lesions of variable age were associated with an overlying fibrinous band in the macula and a peripheral Schlaegel line Fig. a-arrow. Extensive systemic workup was performed. Given the history of EBV and the presence of sub-RPE deposits, lymphoma was ruled out with a chest CT scan. It only revealed reactive cervical lymph nodes. No hepatosplenomegaly was noted. Complete blood count with differential demonstrated a slight increase in lymphocytes (59.9% reference range 10–50%). The rest of the differential was within normal limits. RPR was non-reactive and the FT-ABS was negative. Interferon-Gamma release assay (QuantiFERON-TB gold) was negative. West Nile antibodies were negative, Brain MRI was negative for any CNS lesions or cerebral vasculitis. Liver enzymes were mildly raised: ALT 94 IU/L (reference range 7–52 IU/L) and AST 62 IU/L (reference range 15–40 IU/L). The pattern of elevated aminotransferases and lymphocytosis in the setting of EBV positivity was considered to be consistent with infectious mononucleosis [Given the activity of the MFC, the patient was started on an initial empiric high dose trial of prednisone. As the prednisone was tapered, she was switched to the immunosuppressant, azathioprine. There was significant interval resolution of the inflammatory nature of the lesions in the right eye. Over the following 8 months dramatic improvement was demonstrated resulting in consolidation of the subretinal lesions and decreased inflammation Fig. . Vision During the patient’s course, she self-discontinued the azathioprine. During that three-month interval, there was an increase in the activity of the multifocal lesions evident on her exam and new areas of inflammation Fig.  and a coOur patient’s prior history of EBV- positive mononucleosis was established with the heterophile antibody test which is an agglutination assay that detects anti-red blood cell antibodies produced as part of a polyclonal antibody response occurring during EBV infection. Heterophile antibody tests are rapid, cheap and specific tests with a result that is interpreted as positive or negative (for agglutination) and can be performed from the onset of symptoms of infectious mononucleosis , 7. A poThe development of multifocal choroiditis may be one of the delayed sequelae of EBV infection. Chronic EBV infection has been conjectured to predispose to molecular mimicry and affect various major organ systems including the eye . InteresAzathioprine is a steroid sparing immunosuppressant, mainly used in rheumatologic diseases. The patient had continuous improvement of her inflammatory lesions in the right eye after initiating azathioprine. The visual improvement was somewhat surprising, given the extent of associated fibrosis. The patient showed dramatic improvement in her retinal lesions over 8 months. It seems unlikely that this dramatic visual improvement over 8 months was unrelated to immunosuppression with azathioprine. She had 20/200 vision for a year with persistent active lesions before initiating azathioprine that completely subsided with vision improvement from 20/200 to 20/40 with immunosuppression. This course does not appear to follow the natural history of the disease , rather There is considerable value of titrating immunosuppression to the disease activity as evidenced by the reduced number of lesions along with improvement in vision with azathioprine immunosuppression. In fact, our patient demonstrated test-retest reliability when she self-discontinued the medicine Figs.  and 9 ThIn summary, we present a completely unilateral case of MFC temporally correlated with EBV infection that demonstrated a dramatic improvement in vision and lack of involvement of the fellow eye with aggressive immunosuppression.


We report a case of a 45-year-old male suffering from arterial hypertension who was found to have an aortic coarctation with marked hypertrophic compensatory collateral arterial circulation. Although coarctation is relatively rare, this must be included in the differential diagnosis in patients with arterial hypertension with a positive gradient between upper and lower limbs. A 45-year-old male was evaluated for arterial hypertension. A pressure gradient (18 mm Hg) between upper and lower limbs was noted. Among the various diagnostic examinations, the patient underwent multidetector computed tomography (MD-CT) angiography. This showed an aortic coarctation at the level of isthmus proximal third of thoracic aorta with significant hypertrophic compensatory collateral arterial circulation . At theAortic coarctation in adults is generally recognized via systemic arterial hypertension associated with a pressure gradient between the upper and lower extremities.


There is a known link between myocardial fibrosis as defined by late gadolinium enhancement (LGE), severity of left ventricular remodeling and ventricular arrhythmias in hypertrophic cardiomyopathy (HCM). Noninvasive quantification of fibrosis may offer the possibility for risk stratification. Due to their often diffuse and blurred character these lesions remain difficult to differentiate from healthy myocardium in several cases.Recent studies showed the superiority of Gadobenate dimeglumine (Gd-BOPTA) compared with Gadopentetate dimeglumine (Gd-DTPA) in distinguishing infarcted from viable myocardium which can be explained by the higher relaxivity of Gd-BOPTA. Therefore we hypothesized that Gd-BOPTA may have advantages over Gd-DTPA for depiction of non-ischemic fibrosis.We prospectively enrolled eight Patients with clinically established HCM and positive LGE during clinical routine scan with 0.2 mmol/kg Gd-DTPA (0.5 molar). They underwent a second scan at least 72 hours apart from the first CMR exam with 0.2 mmol/kg Gd-BOPTA (0.5 molar) using the same CMR protocol and sequence parameters. None of the patients had renal failure, coronary artery disease or general contraindications for CMR.LGE was assessed in a short axis stack acquired 15 minutes after contrast administration by using state of the art inversion recovery gradient echo sequence  with a TI adjusted to null signal from normal myocardium. Positive LGE was judged positive if signal intensity was above mean + 2 standard deviations of remote myocardium.Signal intensities of injured myocardium, healthy myocardium, LV cavity and air were measured in identical locations by using anatomical landmarks in dedicated software . Signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated.We observed no complications relating to contrast administration. Both the SNR of injured myocardium  and the CNR between healthy and injured myocardium  were significantly higher with Gd-BOPTA. SNR of LV cavity was significantly higher  with Gd-BOPTA resulting in a poorer contrast between injured myocardium and blood which did not affect the diagnosis since LGE was exclusively non-subendocardial.Gd-BOPTA improves the visualization of non-ischemic fibrosis in HCM. This may offer the potential for a more accurate quantification of focal myocardial fibrosis in this setting.


In vivo1H magnetic resonance spectroscopy studies have found elevated brain glutamate or glutamate + glutamine levels in bipolar disorder with surprisingly high reproducibility. We propose that the elevated glutamate levels in bipolar disorder can be explained by increased pyruvate carboxylase-mediated anaplerosis in brain. Multiple independent lines of evidence supporting increased pyruvate carboxylase-mediated anaplerosis as a common mechanism underlying glutamatergic hyperactivity in bipolar disorder and the positive association between bipolar disorder and obesity are also described. The biotin-dependent pyruvate carboxylase employs pyruvate and the polar molecule bicarbonate instead of COde novo glutamate synthesis via pyruvate carboxylase-mediated anaplerosis in astrocytes  in vivo1H MRS studies of bipolar disorder have found elevated glutamate or glutamate + glutamine with surprisingly high consistency  for the pooled studies that reported glutamate + glutamine in all area of the brain . Analyses of medicated and non-medicated bipolar disorder patients found that the effect size for glutamate level increase in non-medicated patients was much higher  than in medicated patients , consistent with that medications decreased brain glutamate. Increased serum α-ketoglutarate and glutamate and increased glutamate in post-mortem brain tissue samples obtained from bipolar disorder individuals have also been reported (n = 20) were significantly higher in both mania phase  and remission  than matched controls  (n = 15) was found to be significantly higher than in the normal control samples   . In contde novo glutamate synthesis (in vivo1H MRS, serum and post-mortem studies can be readily explained by increased pyruvate carboxylase-mediated anaplerosis in brain of patients with bipolar disorders. This explanation is also supported by the significant comorbidity between bipolar disorder and obesity as described in section Glutamate, Bipolar Disorder, and Comorbid Obesity.It is well-known in the neurochemical literature that brain relies on pyruvate carboxylase-mediated anaplerosis for ynthesis –21. Beca1H MRS studies have reported transient elevation of glutamate or glutamate + glutamine levels in activated brain tissue in response to stimuli or tasks (de novo synthesis of glutamate from glucose (in vivo13C MRS studies of anesthetized rodents found that acute stimulation did not increase pyruvate carboxylase-mediated anaplerotic flux rate in brain (A large body of evidence has consistently demonstrated that there is a significant mismatch or uncoupling between glucose utilization and oxidative metabolism in stimulated brain accompanying increased glutamatergic activities . Similaror tasks . In precor tasks . These r glucose . It shou glucose . Recent in brain , 54.2. As lactate accumulation can only account for a portion of the large decrease in oxygen-to-carbohydrate index accompanying the mismatch between stimulation of glucose utilization and oxidative metabolism, it has been proposed that increased de novo glutamate synthesis via pyruvate carboxylase-mediated anaplerosis contributes to the large decrease in oxygen-to-carbohydrate index when glucose utilization outpaces oxidative metabolism during stimulation of brain activity (The molar ratio of the arterio-venous difference of oxygen to glucose + ½ lactate is commonly referred to as the oxygen-to-carbohydrate index. The oxygen-to-carbohydrate index is reduced when more glucose and lactate are taken up into the brain than are oxidized to COactivity , 51.31P and 1H MRS studies have found reduced oxidative phosphorylation and elevated lactate and glutamate + glutamine levels in brain in bipolar disorder, indicating impaired oxidative metabolism (18F]fluorodeoxyglucose have reported small or no differences between healthy controls and bipolar disorder patients in glucose utilization rate in the prefrontal cortex or brain as a whole (31P and 1H MRS and PET results, taken together, indicate that there is a considerable mismatch between oxidative metabolism and glucose utilization in brain in bipolar disorder. Therefore, the elevated glutamate + glutamine levels are consistent with mitochondrial dysfunction and a chronic mismatch between glucose utilization and oxidative metabolism in bipolar disorder accompanied by incomplete carbohydrate oxidation and increased pyruvate carboxylase-mediated anaplerosis.tabolism , 42, 43. a whole –58. Ther a whole –58. Cons1H MRS was found to be more pronounced with higher body mass index (Bipolar disorder and obesity are positively associated –62 with ss index . In compss index .de novo fatty acid synthesis [(in vivo1H and 13C MRS study of a mouse model of high-fat diet consumption has also found significantly elevated glutamate and glutamate + glutamine levels as well as increased pyruvate carboxylase-mediated anaplerotic flux rate in the hypothalamus of treated animals (Pyruvate carboxylase plays a crucial role in lipogenesis and gluconeogenesis in mammals. It converts pyruvate and bicarbonate into oxaloacetate for further conversion into citrate which is then exported from mitochondria and cleaved in cytosol to supply precursors for nthesis [; Figure nthesis [. Of the nthesis [. The pyrnthesis [. Animal nthesis [. Furthernthesis [. A recen animals . Taken t2 for a variety of biological processes. In the central nervous system carbonic anhydrase inhibition enhances inhibitory neurotransmission. Many anticonvulsants are strong carbonic anhydrase inhibitors. Adjunctive acetazolamide, a sulfonamide carbonic anhydrase inhibitor, improved prophylactic efficacy in 44% of the treatment-resistant bipolar disorder patients (Catalysis by carbonic anhydrase is necessary to speed up the reversible hydration of COpatients . One of patients –79. Of tpatients . Topirampatients .2-fixing enzymes pyruvate carboxylase and acetyl-CoA carboxylase to bicarbonate and decreases pyruvate carboxylase-mediated anaplerosis in peripheral tissues (de novo synthesis of both fatty acids and non-saponifiable lipids (de novo lipogenesis and gluconeogenesis in liver (Inhibition of carbonic anhydrase limits the access of CO tissues . It has e lipids . Carboniin liver , 82. In in liver .2, which is generated by the highly active neuronal oxidative metabolism, from neurons by free diffusion. This distinct distribution of intracellular carbonic anhydrase in brain leads to the conversion of CO2 into bicarbonate primarily in astrocytes, rendering astrocytes as sinks of CO2 (2 fixation by limiting the supply of bicarbonate to pyruvate carboxylase, resulting in reduced TCA cycle intermediate levels and reduced glutamate production (2 hydration catalyzed by carbonic anhydrase and pyruvate carboxylation catalyzed by pyruvate carboxylase (de novo synthesis of glutamate by carbonic anhydrase inhibition may play a significant role in the antiepileptic properties and mood stabilization effects of anticonvulsants that are also carbonic anhydrase inhibitors. Therefore, both mechanistic and clinical studies of carbonic anhydrase inhibition support the proposed connections among bipolar disorder, obesity and pyruvate carboxylase-mediated anaplerosis.Carbonic anhydrase in brain is predominantly expressed in glial and choroid cells –88. The s of CO2 . In cultoduction . Since iboxylase , limitatA single pyruvate carboxylase isoform is expressed in humans and found in mitochondria only . PyruvatPrevious studies have shown that pharmacological inhibition of pyruvate carboxylase by phenylacetic acid markedly reduced hepatic gluconeogenesis in rats . The effin vivo1H MRS. Multiple independent lines of evidence suggest that increased pyruvate carboxylase-mediated anaplerosis is a common mechanism underlying glutamatergic hyperactivity and the significant positive association between bipolar disorder and obesity. As the increased prevalence of obesity in bipolar disorder is associated with illness severity and poor treatment outcomes development of preventive and treatment strategies targeting pyruvate carboxylase-mediated anaplerosis may be warranted.Increased pyruvate carboxylase-mediated anaplerosis can readily explain the elevated glutamate or glutamate + glutamine levels in brain in bipolar disorder observed by JS performed literature analysis and proposed the hypothesis. JT performed literature search. JS and JT wrote the paper. Both authors reviewed the manuscript and agreed on its final version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We employed electrophysiological and fluorescence imaging techniques to describe the characteristics of a novel type of neuron discovered in the mouse dorsal striatum. Transgenic mice that express YFP-tagged channelrhodopsin-2 (ChR2) in neurons driven by the promoter for tyrosine hydroxylase (TH) were used and the intrinsic electrical properties of YFP-positive neurons in the dorsal striatum of these mice were characterized using whole-cell patch clamping in acute brain slices. Passive membrane properties - such as membrane capacitance, resting membrane potential and input resistance -and action potential properties- such as amplitude, kinetics and adaptation - were extracted from raw data files. Filling these neurons with neurobiotin enabled visualization of neuronal morphology via immunohistochemical labeling with streptavidin-conjugated fluorophore. Subsequent two-photon imaging allowed analyses of morphological properties such as somaticsize, dendritic branching  and density of dendritic spines. Unbiased analyses and hierarchical clustering of both morphological and functional data allowed us to identify a previously undescribed type of striatal neuron with unique properties. To facilitate identification of this new cell type, an end-to-end automated electrophysiology pipeline was developed that extracts relevant parameters and determines striatal neuron identity using neural-network based classifiers. These data and the software tool will permit other investigators to identify this novel type of neuron in their studiesand thereby better understand theroles thatthese neuronsplay in dorsal striatum circuitry. Specifications Table1•These data present in detail the basis for identifying a novel type of neuron in the dorsal striatum that has unique intrinsic electrical properties and morphological properties; future studies can use these data as a reference.The software tool that we provide can help researchers identify the novel neuron in their future studies.•Researchers who study striatal circuitry can benefit from these data; in particular, the distinct properties of the novel neuron type lend its unique computational properties that can be examined in modeling studies that utilize our dataset.2•+cells in the dorsal striatum; stimulating currents ranged from −200 to +200 pA, in 50 pA increments. Each current pulse lasted one second.These recordings were used to extract and analyze input resistance, sag amplitude andAP properties .All .abf files are electrophysiology data recorded using pClamp 10.4 (Molecular Devices). They are current clamp recordings from YFP•https://bit.ly/3etT5tZ. These data can also be converted into the open source format Neurodata Without Borders (NWB) and analysed using software provided by the Allen Institute for Brain Science here: https://bit.ly/2Yr906KDespite being a proprietary format, files in the .abf format can be analysed using the free software Clampfit provided by Molecular devices available here: •In addition to data, we have created a freely available tool that allows users to extract electrophysiology data from .abf files in an automated and reproducible manner. A classifier is then used to determine cell identity from the extracted data. All tif. files are two-photon imaging data acquired using an Olympus FV-1000 microscope with a 25x objective (NA=1.05).All imaging dataare Z-stack images.•Analysed data can be found in the figures in Mao et al., 2019 (doi: 10.3389/fncir.2019.00032).3As the data collection process has already been described in the table above, here we will focus on the data analyses.3.1A total of 12 intrinsic electrical properties were used to classify ChR2-YFP expressing neurons of the dorsal striatum; these properties were clustered using unsupervised hierarchical clustering  To cluster the data, we used PCA with singular value decomposition to reduce the dimensionality of our electrophysiology dataset. This was implemented using the pcaMethods package in R. For unsupervised hierarchical clustering, we used the three principle components that accounted for 69% of the total variance in our dataset. We identified the optimal cluster number using silhouette analysis implemented in R and visualized clusters using a dendrogram using the R package Clustvis.3.2l-Measure to obtain parameters such as surface area against path distance and spine density. Dendritic branching was analyzedby Sholl analysis utilizing the Simple Neurite Tracer plugin in ImageJ.For morphological analysis of neurobiotin-labeled neurons, cells were digitally reconstructed using a software suite for reconstruction of neuronal morphology (AdReconstructor). Firstly, pre-processing algorithms were applied to remove common sources of noise, such as non-specific background staining and neurobiotin leakage. Reconstruction of cell morphology was performed using the All Path Pruning algorithms developed by Xiao and Peng (2013) and post-processing measures were applied to ensure reconstructionaccuracy To examine the relationship between electrophysiological and morphological properties, we also performed unsupervised hierarchical clustering of morphological features extracted from 15 digitally reconstructed neurons filled with neurobiotin. The morphological properties extracted were based on definitions used in Scorcioni et al. (2008) 3.3To allow users to interact with the data presented in this paper, we have created a freely available tool that performs automated extraction of electrophysiological parameters used to distinguish striatal TH-interneuron identity  The program is written in the R programming language The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have influenced the work reported in this article.


Arabidopsis thaliana catalyze RNA dependent DNA Methylation pathway along with small interfering RNA. Several developmental functions have also been attributed to DNA methylation. This review will highlight aspects of RdDM pathway dynamics, evolution and functions in seed plants with focus on recent findings on conserved and non-conserved attributes between angiosperms and gymnosperms to potentially explain how methylation has impacted variations in evolutionary and developmental complexity among them and advance current understanding of this crucial epigenetic pathway.RNA Directed DNA Methylation (RdDM) is a pathway that mediates de novo DNA methylation, an evolutionary conserved chemical modification of cytosine bases, which exists in living organisms and utilizes small interfering RNA. Plants utilize DNA methylation for transposable element (TE) repression, regulation of gene expression and developmental regulation. TE activity strongly influences genome size and evolution, therefore making DNA methylation a key component in understanding divergence in genome evolution among seed plants. Multiple proteins that have extensively been studied in model plant  These findings dispute the generalization of similarities among large gymnosperm genomes and point to conifer potentially being unique. However, an anticorrelation is theorized to exist between recombination based elimination of TEs and heterochromatization driven by epigenetic mechanisms as observed in P. abies and fritillaria.  and asymmetrical CHH  which comprises of DEFECTIVE IN RNA DIRECTED DNA METHYLATION 1(DRD1), DEFECTIVE IN MERISTEM SILENCING 3 (DMS3) and RNA DIRECTED DNA METHYLATION 1 (RDM1) . This hypothesis is likely to be supported by the occurrence of NRPE1 the largest subunit of Pol V in conifer P. abies, Ginkgo biloba and Welwitschia mirabilis predominantly display 21 nt siRNA , maintenance of CHG methylation involves crosstalk between CHROMOMETHYLASE 3 (CMT3) and H3K9 histone methyltransferase for demethylation  in CG context and much less in non-CG context apart from gymnosperm Non-CG methylation is also complex and its functions not well characterized. It requires CHROMOMETHYLASES (CMT2&3) which are plant specific methyltransferases that evolved prior to the diversification of land plants. However, CMT2 is hypothesized to have evolved with the angiosperm specific duplication (≥ 236 MYA)  setting and maintenance overlap and incorporate histone modifications  which binds methylated DNA and acetylates histone 3 (H3) lacking H3Kme2 and H3Kme3  compared to wild types  respectively while CHH methylation displayed a correlation coefficient (r = 0.00003) consistent with similar findings that global and gene body mCG and mCHG positively correlate with genome size  and P. abies (70%) are densely methylated as proportion of TEs correlates positively to levels of methylation.We conducted a Pearson R correlation test between repeat element and methylation percentage in different contexts using seven previously studied sample seed plant species Fig. , includiZ. mays with larger genomes than A. thaliana and higher TE content undergo spreading of silencing to genes adjacent to TEs, in particular promoter regions of genes . Methylation in these species therefore plays a role in regulating gene expression and mutations may result in lethal abnormalities.Comparably, DNA methylation regulates gene expression in a genome size dependent manner. Angiosperms such as Gene regulation occurs through repression of transcription by preventing the binding of transcription factors or promoting repressive histone modifications such as H3K9me  demethylation, occurring in the central cell of the female gamete and the vegetative cell of the male gamete  are upregulated leading to gradual demethylation at loci of ripening genes such as CNR   transcription accompanied by hypomethylation in the host plant  and demethylases (ROS1) are recruited to their target loci. Likewise, mechanisms of non-CG methylation maintenance and establishment warrant further comment.Research so far has managed to illuminate majority of the key genes involved in the RdDM pathway and their roles in various stages in model plant Further, the functions of gene body methylation and non-CG methylation remain largely unknown despite them displaying different levels in various tissue types and species (Hisataka et al. 2012; Kawakatsu et al. More studies need to focus on expanding to sequencing methylomes of less studied seed plant species with larger, more complex genomes as well as plants from more clades of land plants for comparison with currently available information. Such research could reveal crucial details about variations in genome evolution dynamics and more DNA methylation functions particularly in relation to seed plants Fig. .Fig. 7SuWMR wrote the initial draft and collected the references. TW restructured the manuscript and increased the scope. QFW contributed to subsequent revisions. All authors read and approved the manuscript.


South African rabies viruses originating from dogs and jackals (canid viruses) are closely related and highlight cross-species transmission events between the two canine species. Rabies due to the canid lyssavirus variant is a significant public health matter in this country. The complete coding sequences of 23 canid lyssaviruses from South Africa are reported here. South African rabies viruses originating from dogs and jackals (canid viruses) are closely related and highlight cross-species transmission events between the two canine species. Rabies due to the canid lyssavirus variant is a significant public health matter in this country. The complete coding sequences of 23 canid lyssaviruses from South Africa are reported here. Lyssavirus genus  (Rabies virus (RABV) is the prototype species of the virales)  and causvirales) . The domvirales) , resultivirales) .de novo assembling of all the reads and mapping of the same reads to existing rabies genomes (GenBank accession numbers KT336433 to KT336436) using default settings in CLC Genomics Workbench v.9 (Qiagen). A single consensus sequence was produced for each sample from an assembly of all the contigs previously generated. The newly obtained consensus sequence was used as a template to map all the original reads in order to estimate the average coverage and possible variants  showing typical signs of central nervous system infection, preserved in glycerol-saline, and transported to the laboratory see . Total v5–ants see . The gents see 5–. The seqts see 5–, 7–9.MT454631 through MT454654 (PRJNA638742.The complete coding sequences were submitted to GenBank and are available under accession numbers MT454654  and BioP


Influenza viruses have perplexed scientists for over a hundred years. Yearly vaccines limit their spread, but they do not prevent all infections. Therapeutic treatments for those experiencing severe infection are limited; further advances are held back by insufficient understanding of the fundamental immune mechanisms responsible for immunopathology. NK cells and T cells are essential in host responses to influenza infection. They produce immunomodulatory cytokines and mediate the cytotoxic response to infection. An imbalance in NK and T cell responses can lead to two outcomes: excessive inflammation and tissue damage or insufficient anti-viral functions and uncontrolled infection. The main cause of death in influenza patients is the former, mediated by hyperinflammatory responses termed “cytokine storm.” NK cells and T cells contribute to cytokine storm, but they are also required for viral clearance. Many studies have attempted to distinguish protective and pathogenic components of the NK cell and T cell influenza response, but it has become clear that they are dynamic and integrated processes. This review will analyze how NK cell and T cell effector functions during influenza infection affect the host response and correlate with morbidity and mortality outcomes. Influenza is a rapidly mutating RNA virus which causes yearly global epidemics characterized by about 1 billion infections and 290,000–650,000 deaths  and subsequent development of acute respiratory distress syndrome (ARDS) leads to death  in the bone marrow . Natural cytotoxicity refers to NK cell killing of target cells in the absence of inhibitory signals from self MHCI molecules Kärre, . ADCC isNK cell inhibitory receptors of the killer cell immunoglobulin-like receptor (KIR) (human) and Ly49 receptor (mouse) families bind self MHC I molecules and inhibit cytotoxicity toward healthy self cells; malignant or infected cells which downregulate MHC I are susceptible to NK cell killing  . Binding to Fas by FasL induces apoptosis in the target cell through a caspase-dependent pathway . Naïve T cells also circulate through the lymphatics and are activated by APCs in the lymph nodes  and humoral (Th2) immunity in response to foreign pathogens. After initial activation, differentiation is driven by cytokine-dependent transcription factor expression  cells. TRM cells are generally identified by the expression of CD69 and CD103, but this method is not entirely accurate as CD69 can be transiently expressed on activated circulating cells and there are some TRM cells which do not express one or both of these markers  NCR1 (mouse), NKp44 and NKp46 (human) encoded by the NK cell costimulatory receptors 2B4 and NTB-A bind to HA and enhance NK cell cytotoxicity, but cannot activate NK cells on their own  binds to the Fc portion of influenza-specific antibodies and initiates ADCC. Studies in humans and macaques demonstrate seasonal influenza infections elicit cross-reactive antibodies to HA and NA epitopes of multiple influenza strains; these antibodies promote NK cell ADCC against infected target cells  and intracellular nucleoprotein (NP) are important for T cell-mediated heterosubtypic immunity to influenza. Significant research in the 1970s and 80s identified T cell immunity to NP and M1 were responsible for cross-reactivity between strains whereas T cell clones specific for HA or NA only mediated strain-specific protection  stimulates NK and Th1 IFN-γ production during influenza infection  following lethal dose influenza infection and found lower IL-17 levels and higher IL-10 levels correlated with increased protection without compromising viral clearance. Interestingly, they only saw these effects when they treated with rIL-27 at peak viral titer or later, compared with worse outcomes if they treated at early stages of infection. Likely, the early inflammatory response is necessary for favorable outcomes, but as adaptive immune cells accumulate in the lung increased inflammation mediates harmful tissue damage  are an alternative model which address some challenges associated with mouse and human studies. They have been successfully infected with numerous influenza strains including 1918 and 2009 pandemic H1N1  and acute respiratory distress syndrome (ARDS) during influenza infection. Developing these drugs is challenging as preventing the inflammatory response entirely would lead to uncontrolled viral replication. It is difficult to identify individual components of inflammatory responses which are directly responsible for immunopathology vs. those which are essential host responses or are simply byproducts of the inflammatory environment.Current anti-viral therapeutics are limited to two approaches: neuraminidase and M2 ion channel inhibitors. Both aim to limit replication and spread of the virus: NA inhibitors target its enzymatic activity and M2 ion channel blockers prevent its proton channel function. These therapies have limited potential, however, because of side effects and the emergence of resistant strains  antibody constructs can activate T cells to kill target cells independent of antigen-specificity. BiTE® antibody constructs are fusions of 2 single chain fragment variable (scFv) molecules: one binds to the antigen of interest and the other binds to CD3ε on cytotoxic T cells. These have been implemented in the cancer immunotherapy field, and M2e-specific BiTE® constructs show protective effects in mice infected with influenza , autologous or allogenic T and NK cells—are promising cancer treatments. CAR T and NK cells can be targeted to a specific antigen by combining an antigen-specific Fv to an intracellular signaling domain which promotes cytotoxicity upon antigen binding (Gross et al., Current therapies targeting NK cell and T cell responses are limited. Anti-inflammatory approaches are more commonly studied because hyperinflammatory responses leading to cytokine storm are a common cause of morbidity and mortality in severe influenza infections. These efforts are hindered by incomplete understanding of the mechanisms behind protective and pathogenic inflammatory responses. Furthermore, the contributions of cytotoxic NK and T cells to the inflammatory response and the effects of anti-inflammatory therapeutics on their functions are poorly understood. Some studies have moved away from efforts to target a single anti-viral mechanism; cell-based immunotherapy approaches could supplement anti-inflammatory therapeutics and promote more efficient viral clearance by cytotoxic NK and T cells. Preliminary data shows that NK cells and T cells can be activated to potently kill influenza-infected cells without contributing to damaging inflammatory responses, but their potential in humans has not yet been evaluated.Despite 2018 marking 100 years since the deadliest influenza pandemic in history, our understanding of influenza virus infections is far from complete. Countless host protection mechanisms have been characterized in mice with much focus on a hallmark of severe disease: hyperinflammatory responses and subsequent cytokine storm. Numerous other studies have attempted to correlate human disease outcomes with these immune mechanisms. NK and T cells are at the forefront of these responses: cytotoxic killing of infected cells is essential for host survival, but NK cell and T cell pro-inflammatory functions may contribute to immunopathology. Through years of research, the field is still unable to clearly distinguish protective responses from harmful ones; Studies addressing this issue will be fundamental to develop effective treatments for severe infections.Some therapeutic approaches attempt to limit inflammation, but until we can distinguish harmful inflammatory mechanisms from necessary anti-viral responses this will be difficult. Others are turning to cell-based therapies to activate NK cell and T cell cytotoxicity against infected cells, but support for these approaches is backed by limited data. Developing effective treatments for severe influenza infections will likely involve a combination of these strategies. Regardless, understanding NK and T cell responses—both cytotoxicity and cytokine production—will undoubtedly be vital to develop effective therapeutics which can improve disease outcomes for patients experiencing severe influenza infections.KF and SP conceptualized the content of and wrote the article. KF generated the figure. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Orthopedic procedures involving the hip have remained challenging for regional anesthesia given the complex innervation, painful nature contributing to difficulty positioning, and a desire to maintain mobility to hasten postoperative recovery. The revision total hip arthroplasty (THA) poses a greater challenge for an effective regional analgesia due to complex surgical approach, scarring from previous surgery and limited patient mobility. The quadratus lumborum (QL) block has demonstrated to provide effective analgesia for primary hip surgery in recent studies. The pericapsular nerve group (PENG) block has also shown to provide analgesia in patients with hip fractures. There is no standard of care regional anesthesia technique for hip surgeries, and the regional practice varies widely among anesthesia providers. This retrospective case series studied the effect of combining the QL with PENG block on the revision THA analgesia. Given the prevalence of osteoarthritis amongst the increasingly aging population and subsequent need for total hip arthroplasty, the frequency of revision hip surgeries is expected to rise. It is estimated that more than 2.5 million patients in the United States alone have had a total hip arthroplasty (THA) . RevisioThe hip has both an anterior and posterior capsule, but the anterior capsule contains predominantly nociceptive fibers while the posterior predominantly has mechanoreceptors. Favoring analgesia without limiting mobility, the anterior capsule is an ideal target for regional anesthesia techniques. In addition, the hip joint is innervated by both the lumbar (L1-4) and sacral (L4-S4) plexus . The perQuadratus lumborum (QL) block has proven effective analgesia for total hip arthroplasty and decreasing opioid requirements for up to 48 hours postoperatively, due potentially to its spread to the paravertebral space . The proWe hypothesized that the combination of PENG with QL block would provide adequate analgesia for the revision THAs, while also limiting motor weakness and thus improving postoperative outcomes. We examined whether addition of pericapsular nerve group (PENG) block with the quadratus lumborum block would provide superior analgesia and would prove to decrease opioid requirements and pain scores.This retrospective case series included patients undergoing revision total hip arthroplasty (THA) at a tertiary academic medical center. Sixteen patients undergoing revision THA provided written consent for the nerve block(s). Eight patients had a QL and PENG block performed and eight patients had only a QL block performed. The nerve block(s) were performed preoperatively with the patient in a supine position for the PENG block and in lateral decubitus position for the QL block. Seven out of eight revision THA patients in the PENG and QL group were done under general endotracheal tube anesthesia (GETA) with a lone patient done under spinal anesthesia. All eight revision THA patients in the QL only group were performed under GETA. The visual analog scores of pain in the post-anesthesia care unit (PACU) and at 6, 12, and 24 hours after surgery were obtained. In addition, cumulative oral morphine equivalent (OME) usage was obtained for PACU, for the first 6 hours, 6-12 hours, and 12-24 hours postoperatively.Ultrasound-guided technique for PENG blockA low-frequency curvilinear transducer was placed in the transverse plane over the anterior inferior iliac spine (AIIS) and moved over inferiorly to visualize the pubic ramus. The femoral artery and iliopubic eminence (IPE) were then visualized Figure . Using iUltrasound-guided technique for transmuscular (anterior) QL blockA low-frequency curvilinear transducer was placed in the axial plane over the spinous process at the level of L4. The probe was moved laterally until the transverse process of L4 was visualized. The “shamrock sign” was then visualized which consists of the following: QL muscle laterally, erector spinae muscle posteriorly, psoas major muscle anteriorly, and transverse process of L4 medially (stem of leaf). Using in-plane technique either a 10 cm echogenic 21g short bevel needle (seven out of 16 patients) or 9 cm 18g Tuohy needle (nine out of 16 patients) was advanced from a posterior  to anterior  direction and 25 ml of local anesthetic 0.25% Bupivacaine was deposited in the fascial plane between the QL and psoas major muscles  and analgesic efficacy . The disIn a recent case series utilizing PENG block for THA, postoperative pain scores and OME use were lower in the group undergoing primary hip surgery compared to revisions . This reTo the best of our knowledge, this is the first retrospective case series study to combine the PENG block with the QL block for revision THA analgesia. The main findings of this study are superior analgesia with the combination blocks as compared to only QL block for revision THAs. Also opioid requirements in the combination group were lower up to at least the first 24 hours. Findings of the opioid sparing analgesic effect in the era of opioid epidemic and preservation of lower limb muscle strength in the era of accelerated physical therapy after THA are therefore encouraging.The anterior lumbar QL block technique deposits local anesthetic deep to the anterior thoracolumbar fascia between the QL and psoas major muscles, in close proximity to the lumbar plexus with potential local anesthetic spread to the paravertebral (PVB) region. The anterior QL block aims to block the lumbar plexus branches, including the lateral femoral cutaneous nerve, which innervates the surgical incision site commonly used in THA approach. A recent cadaveric study and case series concluded that the supra-iliac approach to the anterior QL block involved T10-L3 dermatomal coverage and provided effective analgesia for total hip surgery .Post-operative pain management after THA has always been a challenging goal to achieve. Multiple regional techniques have been used in the past, but there is not a “best proven intervention” for THA analgesia . The maiPostoperative opioid requirements after THA vary depending on the type of regional anesthesia technique used. One study of continuous femoral nerve blocks for THA showed opioid requirement of approximately 160 mg of OMEs and another study of continuous lumbar plexus block showed approximately 114 mg OMEs in first 48 hours [There are some limitations to this case series such as small sample size, retrospective design, and publication bias . Also weAt the same time, this case series explores a new combination approach for THA patients which can be utilized to provide effective analgesia for revision or complex hip arthroplasty. Large sample size studies are warranted to further understand this new technique and also to compare its efficacy with traditional blocks for hip analgesia. Also cadaveric and magnetic resonance imaging studies are required for better understanding of anatomical spread of local anesthetic and nerves covered with PENG block.The PENG plus anterior QL block provided adequate post-operative analgesia for patients undergoing revision THA. This combination block for revision THA reduced pain scores and had opioid sparing effects post operatively. The PENG block is an easy ultrasound-guided regional technique which can be performed in supine position for patient comfort. Further prospective randomized studies are warranted to determine the efficacy of PENG block for analgesia and quality of recovery after hip surgery. Also safety of PENG block alone or in combination with other blocks needs further investigation.


Biosci Rep (2020) 40(8), https://doi.org/10.1042/BSR20201313) would like to correct their Ethics Approval statement. The correct Ethics Approval should be as follows:The study was approved by the ethics committee of the Fourth Hospital of Hebei Medical University. The patients or their relatives gave written informed consent prior to entering the study.The authors of the original article “Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A” (The authors apologise for any inconvenience or misunderstanding that this error may have caused.


Schmorls node (SN) are mostly asymptomatic and incidental findings on MRI. However, sometimes they present like acute onset low back pain or acute exacerbation of chronic back pain after minor trauma.We present rare case of symptomatic infected SN in 67 years female patient presented with complains of low back pain radiating to right buttock. After initial conservative treatment failed subsequent imaging showed significant increase in size of lesion with focal signal changes in disc space gave suspicion of underlying secondary pathology. Patient operated for complete excision of lesion. Histopathological report was suggestive of pyogenic vertebral osteomyelitis. Patient improved well postoperatively.Most of the time acute SN responds well to conservative treatment; however rapid deterioration of symptoms or persistent severe pain should give suspicion of underlying secondary pathology. Schmorl’s node (SN) is herniation of intervertebral disc into vertebral body through end plate defect. They first described by Christian Schmorl in 1927. SN are mostly asymptomatic and incidental findings on MRI; however sometimes they present like acute onset low back pain or acute exacerbation of chronic back pain after minor trauma , degenerWe present atypical presentation of acute symptomatic SN with infective pathology. There are no reports in the literature regarding the occurrence, imaging follow-up, treatment and outcome of symptomatic acute infective SN till date.Sixty-seven years female patient presented to our hospital with complains of low back pain radiating to right buttock since 1 month with visual analogue scale (VAS) score 7. There was no associated fever or significant trauma in recent past. She had no other medical or surgical history in the past. Clinically, there was no tenderness over lumbar spine. Patient was neurologically intact.A plain radiograph of lumbar spine was showing L4–5 narrowing of disc space with mild degenerative scoliosis. Dynamic plain radiograph does not show any features of instability. Computed tomography (CT) scan showed osteolytic bone lesion at inferior end plate of L3 vertebral body Fig. . InitialWe performed partial corpectomy L3 and expandable cage insertion through lateral retroperitoneal approach with posterior bone cement augmented percutaneous pedicle screw fixation L2-L4. Sample sent for histopathological examination and microbiology culture. Post operative MRI showed complete excision of lesion with persistent marrow signal changes at anterio-superior part of L4 vertebral body (Fig. Most of the SNs are asymptomatic and incidental finding . It is rVarious theories have been proposed to explain the pathogenesis of SN in which widely accepted theory is axial load model proposed by Dar et al.  They proConventional radiograph has very limited value for diagnosing SNs. It is useful only in late stage of SN where sclerosis appear around lesion. These findings can be seen early and in more details on CT scan. Alternatively, Presence of bone oedema on Dual energy CT can suspect the infective/inflammatory pathology . MRI is Conservative line of management always will be first line of management in symptomatic SN. Symptoms usually resolves within 2 to 6 months; however marrow edema on MRI gradually subsides over period of 3 to 12 months . We alsoPeng et al.  did segmTypical Histopathological examination of pyogenic vertebral osteomyelitis shows inflammatory cell infiltration, vascular proliferations with granulation tissue, fibrosis, thrombosed blood vessels and bony necrosis depending upon stage of disease; as seen in current case report Fig. . It was In this study, we present the first report of infectious SN, which is very similar to acute non-infected Symptomatic SN at the beginning. Therefore, if infected SN is suspected based on laboratory studies Careful follow-up observation is essential. However, the clinical course along with MRI and CT findings and histological images are more suggestive of infective pathology instead of degeneration hence managed aggressively with excision of infective focus.SN is always considered as one of the differential diagnosis of acute low back pain. Most of the time patient responds well to conservative treatment with analgesics and bed rest. Rapid deterioration of symptoms or persistent severe pain despite of conservative treatment should give suspicion of underlying another secondary pathology. It should be aggressively investigated and treated without further delay. MRI is investigation of choice for early diagnosis as well as to differentiate between symptomatic and asymptomatic SN. Currently there is no established treatment modality. Future investigations should address interventions for treating symptomatic SNs.


Jia and colleagues have concluded that plasma endostatin shows a useful value for predicting failure to recover from acute kidney injury (AKI) . They stEndostatin is a useful biomarker to predict recovering failure from acute kidney injuryHui-Miao Jia, Wen-Xiong LiWe appreciate the comments of Honore et al. on our article.In this study, endostatin plasma concentration was detected immediately after acute kidney injury (AKI) diagnosis and before the renal replacement therapy (RRT) started and showed a useful value to predict the recovering from AKI failure. Early prediction aims to enable individual treatments and effective interventions that may improve clinical outcomes. Endostatin is a 28-kDa molecule that can be removed by a high flux membrane . Differe


Flow diverting stents have been used safely and effectively for the treatment of intracranial aneurysms, particularly for large and wide necked aneurysms that are not amenable to conventional endovascular treatment with coiling. The Surpass Streamline device  is a relatively new and unique flow diverting stent which maintains constant device mesh density over varying vessel diameters. This may potentially provide advantages compared to other flow diverting stents in achieving aneurysmal occlusion.Two patients with VRAA were treated using the Surpass Streamline device. The first patient was a 65-year-old male with an incidental 2.4 cm aneurysm originating from the hepatic artery near the gastroduodenal artery (GDA). The second patient was a 56-year-old male with an incidental 1.9 cm renal aneurysm arising from an anterior inferior segmental branch of the left renal artery. A Surpass flow diverting stent was used to successfully exclude the aneurysm neck in both cases.Reduced flow was achieved in one patient . Preserved flow and stagnation  was achieved in the other. There was preserved distal flow in the parent arteries. No immediate complications were encountered in either case. Complete occlusion of both aneurysms was seen on follow up CT angiographic imaging within 8-weeks.The Surpass flow diverting stent can be used safely and effectively to treat VRAA. It should be considered in unruptured large and giant wide necked VRAAs aneurysms. Additional large prospective studies are required for further validation. Flow diversion is a well-established technique for the treatment of intracranial aneurysms with high technical success and low recurrence rates  are more frequently being detected with the increasing use of cross sectional imaging. They are rare with an estimated prevalence of 2–3% . The size (> 2 cm) and lobulatedmorphology suggested high risk of rupture and so the patient was referred for endovascular treatment. The presence of a wide neck made conventional coil embolization less desirable  was placed into the right common femoral artery. Initial angiogram of the celiac artery using a 6-French Cobra-2 catheter  demonstrated a wide-necked aneurysm arising from the terminiation of common hepatic artery involving the origin of the GDA  was placed into the right common femoral artery. Angiography via a 6-French Cobra-2 catheter  demonstrated a 1.9 cm wide-necked renal artery aneurysm arising from an anterior inferior segmental branch of the left renal artery Fig. a. SystemBoth procedures were uncomplicated and technically successful with no immediate or short-term complication. At 8 and 3 weeks follow up CTA imaging respectively both aneurysms were completely occluded Figs.  and 5. DThe use of endovascular procedures as first line treatment for the management of VRAA is becoming increasingly popular , liquid embolic agents such as n-butyl cyanoacrylate or ethylene vinyl copolymer (Onyx) and precipitating hydrophobic injectable liquid (PHIL) , Silk , Flow Reduction Endoluminal Device , p64  and LEO Baby . The unique braided design of these devices produces low radial opening forces to facilitate navigation while greater metal coverage and reduced porosity encourages aneurysm occlusion. Rapid flow reduction promotes thrombosis within hours to days, and sometimes months, and provides a scaffold for neointimal proliferation over the aneurysm neck  with no reported mortalities  and the presence of important arterial branches precluded the use of conventional coil embolization, standard self-expanding or balloon-expandable covered stents. The Surpass flow diverter was ideally suited obviating the risk of distal end organ ischaemic complications. Recent publications demonstrate successful treatment of visceral aneurysms with stents with flow diverting properties, where similarly, parent and side branch patency is deemed important. The double-layer micromesh Roadsaver, similar to the Surpass, has increased mesh density and reduced poor size resulting in improved aneurysm occlusion  indicating successful treatment. Importantly, in patient 2 no change in flow was observed. However, there was stagnation of contrast within the aneurysm (OKM Grade A3). The reduction in flow and stagnation highlights the advantage of the Surpass flow diverter which allows for preservation of side branch and perforator vessels. It is important for operators using this device to be aware that it can take hours to days to achieve complete aneurysm occlusion. At 8 week and 3 weeks respectively both aneurysms were completely occluded on follow up imaging. Systemic anticoagulation and antiplatelet agents may interfere with this; however, a short course of dual antiplatelet therapy is required to maintain stent patency until endothelialization occurs.We advocate for the use of dual antiplatelet therapy to prevent in-stent thrombosis when using flow diverting stents for peripheral aneurysms. Both patients were administered dual antiplatelet therapy for 1 week prior to the procedure (100 mg Aspirin and 75 mg clopidogrel) with the plan to continue this for 6 months postprocedure, at which point clopidogrel is ceased. Most studies evaluating flow diverting stents have used similar regimes and premature cessation of clopidogrel has been linked with a higher risk stent thrombosis, even at 3 months  immediately following stent deployment. Importantly, the Surpass flow diverter is limited to use in smaller vessels with a maximum vessel diameter of 5.3 mm with the 5 mm device. Consideration should also be given to material costs compared to conventional endovascular methods.The Surpass flow diverting stent demonstrates early safety and efficacy in the treatment of VRAA. This novel report of its use in the peripheral vasculature highlights its expanding role extra-cranially. It should be considered in those aneurysms with wide necks or arising from difficult parent vessel anatomy with the constant mesh density potentially providing improved flow reduction over a range of vessel diameters when compared to other commercially available flow diverting stents. Its use should be further validated in larger case series or prospective studies. There is scope for future work to evaluate the long-term clinical outcomes with this device.