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Patients with paroxysmal nocturnal hemoglobinuria (PNH) are susceptible to complement-mediated intravascular hemolysis and thrombosis. Factor H (FH) is the main regulator of the complement alternative pathway, which protects cells from unwanted complement-mediated damage. Although FH is not a glycosylphosphatidylinositol-linked molecule, it may play a role in PNH. We sought to determine if rare germline variants in complement factor H (CFH) affect the PNH course, screening 84 patients with PNH treated with eculizumab for rare variants in CFH, CFI, and C3 genes. We compared the allelic frequencies with populational data and a geographically-matched control group, looking for an association between presence of the variants and treatment response (transfusion independence by 6 months). Sixteen patients presented rare variants, 9 in CFH (10.7%). Germline CFH variants were more frequent among patients with PNH than among controls (P = .02) or public data (P < .001) and were more likely to be transfusion-dependent at 6 months after eculizumab initiation (P = .015). With a median follow-up of 5.8 years, 8 of 9 patients with the CFH variant received transfusions, and 2 developed thromboses. None of the patients with the CFH variant had severe aplastic anemia from eculizumab initiation until 6 months. We demonstrated for the first time that rare CFH variants are over-represented among patients with PNH and that germline genetic background may affect the response to eculizumab.

Intravenous immunoglobulin (IVIg), which is used to treat multiple neurological conditions, may be associated with serious adverse reactions. The individual neurological disease characteristics associated with adverse reactions, along with strategies to prevent and treat adverse reactions, are uncertain. A systematic review was conducted of the databases PubMed, Embase, and Cochrane Library to summarise studies that report adverse reactions of IVIg therapy in patients with neurological disease. There were 65 studies included in the review. The reported rates of adverse reactions vary widely, but the best evidence suggests rates between 25 and 34% per patient. Common adverse reactions include headache and laboratory abnormalities. Less common but serious adverse reactions included thromboembolic complications and anaphylaxis. Overall, there is a lack of high-quality comparative data to definitively determine if any specific neurological indications are associated with a higher risk of adverse reactions. However, individual neurological disease characteristics possibly associated with an increased likelihood of adverse reactions include limited mobility (as in certain neuromuscular conditions), paraproteinaemia (as in certain peripheral neuropathies), and cardiomyopathy (as in certain myopathies). There is limited evidence to support the effectiveness of prevention and treatment strategies, which may include modification to dose, reduced infusion rate, and premedication. Further studies regarding methods to prevent and treat IVIg-ARs in neurology patients are required.

Introduction: Machine learning has previously been applied to text analysis. There is limited data regarding the acceptability or accuracy of such applications in medical education. This project examined medical student opinion regarding computer-based marking and evaluated the accuracy of deep learning (DL), a subtype of machine learning, in the scoring of medical short answer questions (SAQs). Methods: Fourth- and fifth-year medical students undertook an anonymised online examination. Prior to the examination, students completed a survey gauging their opinion on computer-based marking. Questions were marked by humans, and then a DL analysis was conducted using convolutional neural networks. In the DL analysis, following preprocessing, data were split into a training dataset (on which models were developed using 10-fold cross-validation) and a test dataset (on which performance analysis was conducted). Results: One hundred and eighty-one students completed the examination (participation rate 59.0%). While students expressed concern regarding the accuracy of computer-based marking, the majority of students agreed that computer marking would be more objective than human marking (67.0%) and reported they would not object to computer-based marking (55.5%). Regarding automated marking of SAQs, for 1-mark questions, there were consistently high classification accuracies (mean accuracy 0.98). For more complex 2-mark and 3-mark SAQs, in which multiclass classification was required, accuracy was lower (mean 0.65 and 0.59, respectively). Conclusions: Medical students may be supportive of computer-based marking due to its objectivity. DL has the potential to provide accurate marking of written questions, however further research into DL marking of medical examinations is required.

Our understanding and management of atypical hemolytic uremic syndrome (aHUS) have dramatically improved in the last decade. aHUS has been established as a prototypic disease resulting from a dysregulation of the complement alternative C3 convertase. Subsequently, prospective nonrandomized studies and retrospective series have shown the efficacy of C5 blockade in the treatment of this devastating disease. C5 blockade has become the cornerstone of the treatment of aHUS. This therapeutic breakthrough has been dulled by persistent difficulties in the positive diagnosis of aHUS, and the latter remains, to date, a diagnosis by exclusion. Furthermore, the precise spectrum of complement-mediated renal thrombotic microangiopathy is still a matter of debate. Nevertheless, long-term management of aHUS is increasingly individualized and lifelong C5 blockade is no longer a paradigm that applies to all patients with this disease. The potential benefit of complement blockade in other forms of HUS, notably secondary HUS, remains uncertain.

Background Interhospital transfers of surgical patients are an independent risk factor for mortality. The Australian and New Zealand Audit of Surgical Mortality (ANZASM) aims to improve surgical care through assessment of all cases of surgical mortality. This study aimed to describe common clinical management issues that contributed to interhospital transfer patient mortality. Methods Data for all surgical patient mortality in Australia (except New South Wales) that underwent interhospital transfer between 1 January 2010 and 31 December 2019 were extracted from ANZASM. The surgeons’ reports and assessors’ evaluations were examined to identify clinical management issues. Thematic analysis was performed to develop pertinent themes and subthemes. Results Some 8679 patients were identified over the 10-year period. Of these, 2171 (25.0 per cent) had 3259 clinical management issues identified. Prominent themes were operative design (n = 466, 14.3 per cent), decision to operate (n = 425, 13.0 per cent), medical conditions (n = 344, 10.6 per cent), diagnosis (n = 326, 10 per cent), transfer (n = 293, 10.0 per cent), intraoperative issues (n = 278, 8.5 per cent), inadequate assessment (n = 238, 7.3 per cent), communication (n = 224, 6.9 per cent), delay in recognizing complications (n = 180, 5.5 per cent), coagulopathy (n = 151, 4.6 per cent), insufficient monitoring (n = 127, 3.9 per cent), infection (n = 107, 3.3 per cent), and hospital resources (n = 100, 3.1 per cent). Assessors considered 58.4 per cent of clinical management issues (n = 1903) probably or definitely preventable. Conclusion This study identified 13 themes of potentially avoidable management issues present in surgical mortality following interhospital transfers. Quality-improvement initiatives targeting these areas may improve surgical patient outcomes.

A state-of-the-art Rietveld refinement strategy is proposed to derive the instrumental resolution function (IRF) for a ball-mill setup for time-resolved in situ (TRIS) synchrotron XRPD.

The purpose of this work is to revisit the history of surgical treatment for obstructive hypertrophic cardiomyopathy (oHCM) over the last 60 years, in the light of advancing knowledge of the pathophysiology of obstruction.In this narrative review the contribution of the different surgical approaches to the field will be assessed in our personal experience in Florence.Septal myectomy is the treatment of choice in patients with obstructive hypertrophic cardiomyopathy who remain symptomatic despite optimal medical treatment. Over the decades, numerous "theme variations" of the Morrow operation have been proposed, each of them targeting a specific pathophysiological determinant of left ventricular outflow tract obstruction.Precision surgery in oHCM patients today depends on the ability of the surgeon to combine and master these variations, with the bird's eye view allowed by climbing on the shoulders of giants.

Three new polycatenated mixed-ligand MOFs containing fluorene and naphthalene scaffolds have been solvothermally synthesized. Their solid-state luminescence has been investigated showing a Förster resonance energy transfer involving the two linkers.

Deep learning may be able to assist with the prediction of neurosurgical inpatient outcomes. The aims of this study were to investigate deep learning and transfer learning in the prediction of several inpatient outcomes including timing of discharge and discharge destination.Data were collected on consecutive neurosurgical admissions from existing databases over a 15-month period. Following pre-processing artificial neural networks were applied to admission notes and ward round notes to predict four inpatient outcomes. Models were developed on the training dataset, before being tested on a hold-out test dataset and a validation dataset.1341 individual admissions were included in the study. Using transfer learning and an artificial neural network an area under the receiver operator curve (AUC) of 0.81 and 0.80 on the derivation and validation datasets was able to be achieved for the prediction of discharge within the next 48 hours using daily ward round notes. This result is in comparison to an AUC of 0.71 and 0.68 using an artificial neural network without transfer learning for the same outcome. When the artificial neural network with transfer learning was applied to the other outcomes AUC of 0.72, 0.93 and 0.83 was achieved on the validation datasets for predicting discharge within the next 7 days, survival to discharge and discharge to home as a destination.Deep learning may predict inpatient neurosurgery outcomes from free-text medical data. Recurrent predictions with ward round notes enable the use of information obtained throughout hospital admissions in these estimates.

BRCA1-associated protein 1 (BAP-1) is a deubiquitylase that functions as a tumor suppressor, regulating multiple cellular processes including cell cycle control, differentiation, cell death, and DNA repair. BAP-1-inactivated melanocytic tumors (BIMTs) have recently been described and are characterized by epithelioid cytomorphology, are often clonal in appearance, and typically do not recur or show malignant transformation on follow-up.To describe the histopathologic and molecular characterization of five cases of BAP-1-inactivated cutaneous malignant melanomas.The archives at two separate institutions were retrospectively searched for tumors classified as melanoma with loss of BAP-1 via immunohistochemistry. Five cases were identified. These cases were classified as malignant melanoma based on cytomorphology, immunohistochemistry, and ancillary molecular testing. The clinical demographics were recorded, along with the histomorphologic features of each case. Genomic analysis for all cases was performed via OncoScan.The five reviewed cases consisted of two females and three males ranging from 67 to 74 years in age. Molecular characterization of each case was performed using OncoScan. Microarray assay showed that there was a complete deletion of 3p in all cases, BRAF V600E mutation in two cases, NRAS missense variant in one case, and loss of 9p in three cases. All cases showed malignant copy number alterations.Herein we describe five cases of BAP-1-inactivated melanomas confirmed by histomorphology and immunohistochemistry, all of which show malignant copy number profiles including loss of 3p. In addition, we provide a case of a likely BIMT showing progression to BAP-1-inactivated melanoma on a 16-year follow-up.

Nudge theory has influenced the behaviour of millions of individuals across the world; however, the potential power of this approach has yet to be fully utilised in the field of inpatient cardiac surgery. The nudge theory also presents multiple nonalert choice architecture modifications that may be employed. Choice architecture is already influencing decisions made in hospitals every day, whether it has been deliberately designed to promote beneficial behaviours or not. Decision making for cardiac surgery inpatients is already subject to inherent choice architectures, which may be amenable to nudges. The types of choices to which nudges may be employed in the inpatient surgical setting are numerous and may be relevant to medical officers, nursing staff, allied health staff, and patients. Through the strategic development and robust evaluation of choice architecture modification, using the principles of the nudge theory, further optimisation of cardiac surgery inpatient management may be achieved.

SUMMARY Statement of problem Customized glass fiber posts using CAD-CAM technology have been suggested for restoring endodontically treated teeth. However, how weakened or non-weakened roots restored with anatomical CAD-CAM posts behave under cyclic fatigue is not clear. Objective To evaluate the load-bearing capacity under fatigue (fatigue failure load [FFL], the number of cycles for failure [CFF], and survival probabilities) and fracture pattern of weakened and non-weakened roots restored with CAD-CAM fiber post and cores, metal cast-post-core, and prefabricated fiber post and resin core. Methods and Materials A total of 60 crack-free bovine incisor roots (13 mm in length) with standard geometry were obtained and randomly allocated considering the factor “root condition” in two levels (weakened and non-weakened). Thus, half of the roots were weakened to obtain a wall thickness of 0.5 mm. After that, the endodontic treatment was executed, all roots embedded with acrylic resin and the specimens randomly allocated (n=10) considering the factor “post system” in three levels (CAD-CAM: CAD-CAM milled glass-fiber post and core; MBC: metallic-based post and core; and FRC: prefabricated glass-fiber post and composite resin core). The posts were luted with a dual-cure self-adhesive luting agent. Then, all teeth received a metallic crown. An initial load of 100 N at 20 Hz for 5000 cycles was applied for the step-stress fatigue test, followed by incremental steps of 50 N for 20,000 cycles each step, up to failure. A fracture pattern analysis was performed. Results CAD-CAM fiber post (FFL: 865 N; CFF: 311,000 cycles) presented similar fatigue performance (p>0.05) to FRC (FFL: 925 N; CFF: 335,000 cycles), with 100% of repairable fractures for non-weakened roots; however, both groups presented worse performance than MBC (p0.05; FFL: 1035-1170 N; CFF: 379,000-433,000 cycles), with a high rate of catastrophic failures. Conclusions CAD-CAM fiber post presented similar fatigue performance to MBC and FRC approaches when restoring weakened roots. CADCAM was similar to FRC when restoring non-weakened roots, while MBC enhanced fatigue properties in this scenario.

The purpose of this study is to present current dental ceramic materials and processing methods. The clinical indication was emphasized on basis of the material's microstructure and composition. Studies of ceramic characterization were also discussed, as they impact the clinical indication and serve as a parameter for the development of new materials. The novel strategies were mostly found aiming to mimic the natural dental structures, provide mechanical reliability, and develop predictable restorations in terms of adaptation and design.

Evidence indicates most people were resilient to the impact of the COVID-19 pandemic on mental health. However, evidence also suggests the pandemic effect on mental health may be heterogeneous. Therefore, we aimed to identify groups of trajectories of common mental disorders' (CMD) symptoms assessed before (2017-19) and during the COVID-19 pandemic (2020-2021), and to investigate predictors of trajectories.We assessed 2,705 participants of the ELSA-Brasil COVID-19 Mental Health Cohort study who reported Clinical Interview Scheduled-Revised (CIS-R) data in 2017-19 and Depression Anxiety Stress Scale-21 (DASS-21) data in May-July 2020, July-September 2020, October-December 2020, and April-June 2021. We used an equi-percentile approach to link the CIS-R total score in 2017-19 with the DASS-21 total score. Group-based trajectory modeling was used to identify CMD trajectories and adjusted multinomial logistic regression was used to investigate predictors of trajectories.Six groups of CMD symptoms trajectories were identified: low symptoms (17.6%), low-decreasing symptoms (13.7%), low-increasing symptoms (23.9%), moderate-decreasing symptoms (16.8%), low-increasing symptoms (23.3%), severe-decreasing symptoms (4.7%). The severe-decreasing trajectory was characterized by age 60 years, female sex, low family income, sedentary behavior, previous mental disorders, and the experience of adverse events in life.Pre-pandemic characteristics were associated with lack of response to assessments. Our occupational cohort sample is not representative.More than half of the sample presented low levels of CMD symptoms. Predictors of trajectories could be used to detect individuals at-risk for presenting CMD symptoms in the context of global adverse events.

Introduction The occurrence of malignant ocular melanomas is uncommon, and the association of these tumors with intradural extramedullary metastases in the cervical spine is exceptionally rare. Case Report A 62-year-old woman undergoing adjuvant chemotherapy after surgical treatment for malignant ocular melanoma begins to experience vertigo and headache. The condition evolved with walking difficulty and neck pain that was exacerbated by swallowing and mobilizing the neck. During her ocular melanoma follow-up, lesions suggestive of metastasis in the central nervous system were not evidenced until this moment. The physical examination did not show significant findings, and a cranial computed tomography scan was performed. The image showed a hyperdense lesion with postcontrast enhancement inside the vertebral canal, at the level of C1-C2. Spinal decompression and subtotal resection were performed. The anatomopathological report revealed intradural metastasis of a malignant ocular melanoma. The postoperative period was uneventful, with significant pain improvement and no recurrences. Conclusion Intradural extramedullary metastases are rare presentations of malignant ocular melanoma. In addition, less than ten similar cases have been reported in the literature. When caring for a patient with melanoma and neurological deficits, always consider evaluating central nervous system metastases. To evaluate this patient, a sensible and detailed neurological exam is extremely important to recognize the location of the deficits and guide the best approach, such as an indication for surgery.

Introduction Ventriculoperitoneal (VP) shunt is commonly used in the treatment of hydrocephalus and may present complications in up to 30% of patients. The present report addresses an uncommon complication in the abdominal cavity, in which the catheter caused extrinsic compression of the gastric wall. Case report A 30-year-old man presented a decreased level of consciousness, associated with severe headache and vomiting. He had a history of congenital neurotoxoplasmosis and VP shunt insertion at 7 years of age. Imaging exams demonstrated the formation of an encapsulated retrogastric pseudocyst and extrinsic compression of the gastric wall by a VP shunt catheter. Through videolaparoscopy, decompression of the gastric wall and removal of the pseudocyst were performed, with the reestablishment of the drainage of cerebrospinal fluid. An analysis of the distal fragment of the removed catheter revealed obstruction by fibrotic material. The patient was discharged with a reestablished baseline after four days of hospitalization. Comments The literature shows that ∼ 47% of the complications presented by patients are related to the distal end of the catheter, and 8.2% of these come from migration to the abdominal cavity. However, there is an extreme paucity of studies that demonstrate extrinsic compression of the gastric wall by a VP shunt catheter. Therefore, we suggest that further studies on complications involving the VP shunt be performed to improve diagnostic and therapeutic results, in addition to complementing the literature on this complication.

Objectives: The study evaluated the bond strength, degree of conversion and fracture pattern of the hybrid layer in cement-dentin adhesion techniques. Materials and Methods: Bovine teeth dentin blocks were divided according to the cementation techniques: G1- Conventional three-step adhesive and dual-curing resin cement; G2- One-step self-etch adhesive and dual-curing resin cement; G3-Self-adhesive resin cement; and G4- Self-adhesive primer and dual-curing resin cement. Specimens were submitted to thermal cycling, chemical aging or water storage. Bond strength was evaluated by testing machine; fracture pattern observed by optical microscopy, and degree of conversion evaluated in micro-Raman spectrophotometer. Data were analyzed by two-way ANOVA and Tukey's test (α=0.05). Results: G1 showed greatest bond strength (p

We assessed the presence of V, Cr, Ni, Cu, Zn, As, Se, Sb, Cd, and Pb in white lupin samples cultivated in Southern Italy by the validation of an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) method. The ICP-MS method validation showed satisfactory values of linearity (r2 > 0.999), recovery (87.4–100.7%), repeatability, and reproducibility values. Zinc was the most abundant element; showing mean concentrations of 0.778 ± 0.09 mg/Kg wet weight (w.w.) and a maximum of 1.013 mg/Kg w.w., followed by copper (0.191 ± 0.05 mg/Kg w.w.). Among the non-essential elements, important levels of cadmium were found (0.017 ± 0.004 mg/Kg w.w.), with 28% exceeding the limits set by the EU Regulation. The results of this work confirm the role of white lupins and other legumes in reducing the pH of the soil, increasing the exchangeable forms of Cd. This work also provides the first data on the nutritional and antinutritional properties of white lupins cultivated in Italy.

Evaluating overall survival in randomized controlled trials (RCTs) can often be confounded by bias introduced by treatment switching. SERAPHIN was a large RCT that evaluated the effects of long-term treatment with the endothelin receptor antagonist macitentan in patients with pulmonary arterial hypertension. In an intent-to-treat (ITT) analysis, a non-significant decrease in the risk of all-cause mortality up to study closure was reported with macitentan 10 mg versus placebo. As patients could switch treatment when experiencing symptoms of disease progression, this analysis attempts to adjust for the confounding effects on overall survival.The inverse probability of censoring weighted (IPCW) and rank-preserving structural failure time (RPSFT) models were used to estimate the treatment effect on overall mortality had there been no treatment switching in SERAPHIN. Time to all-cause death was evaluated up to study closure. Treatment switching was defined as patients in the placebo group switching to open-label macitentan 10 mg, and patients in the macitentan 10 mg group prematurely discontinuing macitentan.By study closure, 73.2% (183/250) of patients in the placebo group had switched to macitentan 10 mg. Among these patients, exposure time to macitentan 10 mg represented 28.2% of total study treatment exposure (cumulative exposure 134.6 patient-years). At study closure, 24.8% (60/242) of patients in the macitentan 10 mg group were not receiving open-label macitentan; mean time not receiving macitentan was 44.3 weeks. The adjusted hazard ratios (HR) for overall survival using the IPCW and RPSFT methods were lower (HR 0.42, 95% confidence interval [CI] 0.22, 0.81; p = 0.009, and HR 0.33, 95% CI 0.04, 2.83, respectively) than the ITT unadjusted HR (0.80, 95% CI 0.51, 1.24).These results from the current analyses indicate that in SERAPHIN, the standard ITT analysis was confounded by treatment switching resulting in an underestimation of the benefit of macitentan 10 mg on overall survival. By adjusting for switching, the IPCW and RPSFT models estimated a 58% and 67% reduction in risk of mortality, respectively, with macitentan 10 mg versus placebo.ClinicalTrials.gov identifier: NCT00660179.

Background Depression is the leading cause of global disability and can develop following the change in body image and functional capacity associated with stoma surgery. However, reported prevalence across the literature is unknown. Accordingly, we performed a systematic review and meta-analysis aiming to characterise depressive symptoms after stoma surgery and potential predictive factors. Methods PubMed/MEDLINE, Embase, CINAHL and Cochrane Library were searched from respective database inception to 6 March 2023 for studies reporting rates of depressive symptoms after stoma surgery. Risk of bias was assessed using the Downs and Black checklist for non-randomised studies of interventions (NRSIs), and Cochrane RoB2 tool for randomised controlled trials (RCTs). Meta-analysis incorporated meta-regressions and a random-effects model. Registration: PROSPERO, CRD42021262345. Results From 5,742 records, 68 studies were included. According to Downs and Black checklist, the 65 NRSIs were of low to moderate methodological quality. According to Cochrane RoB2, the three RCTs ranged from low risk of bias to some concerns of bias. Thirty-eight studies reported rates of depressive symptoms after stoma surgery as a proportion of the respective study populations, and from these, the median rate across all timepoints was 42.9% 42.9% (IQR: 24.2–58.9%). Pooled scores for respective validated depression measures (Hospital Anxiety and Depression Score (HADS), Beck Depression Inventory (BDI), and Patient Health Questionnaire-9 (PHQ-9)) across studies reporting those scores were below clinical thresholds for major depressive disorder according to severity criteria of the respective scores. In the three studies that used the HADS to compare non-stoma versus stoma surgical populations, depressive symptoms were 58% less frequent in non-stoma populations. Region (Asia–Pacific; Europe; Middle East/Africa; North America) was significantly associated with postoperative depressive symptoms (p = 0.002), whereas age (p = 0.592) and sex (p = 0.069) were not. Conclusions Depressive symptoms occur in almost half of stoma surgery patients, which is higher than the general population, and many inflammatory bowel disease and colorectal cancer populations outlined in the literature. However, validated measures suggest this is mostly at a level of clinical severity below major depressive disorder. Stoma patient outcomes and postoperative psychosocial adjustment may be enhanced by increased psychological evaluation and care in the perioperative period.

With more than one billion people exposed to floods throughout the world, this natural hazard is the most common and devastating one, resulting in loss of lives and damaging personal properties or sensitive infrastructures. Numerical models have become essential to forecast and to mitigate their consequences, but they remain uncertain mainly due to the lack of high-resolution data and the inherent uncertainties related to the simplified representation of natural phenomena.The growing availability of satellite observations distributed in time and space is a valuable source of information for improving flood modelling. Additional data like water level or flood extent can be extracted and used to calibrate numerical models.This study proposes to analyse the potential of remote sensing data as a complement to in-situ observations (from hydrometric stations) in the calibration process of shallow-water flood numerical models. A two-dimensional twin experiment of an extreme flood event overflowing into the floodplains is carried out on a 50 km reach on the Garonne River in France between Tonneins and La Réole. The roughness coefficients are computed as solutions to an inverse problem mixing both in-situ (pointwise and high-frequency) and satellite observations (spatially distributed but low-frequency) data. Data assimilation combining uncertain model simulations and observations has proven efficient for improving hydraulic models. However, an open question is the choice of the best information to assimilate (water level or/and flood extent maps) into the hydraulic models. We study this problem by testing different assimilation configurations. The satellite observations are not considered perfect, so the numerical solutions are compared with different noise levels.

Liver transplantation (LT) is the only effective treatment for acute-on-chronic liver failure (ACLF), but it is limited by organ availability. This study aims to identify predictive factors of mortality for LT candidates based on parameters measured at the admission into the ICU.Sixty-four patients diagnosed with ACLF, admitted consecutively into ICU between 2015 and 2019, were retrospectively enrolled in the study. Data were assessed using univariate and multivariate regression analyses to identify risk factors for inhospital mortality and 1-year mortality.A total of 67% of patients were diagnosed with ACLF grade 3, and 25 and 8% with grades 2 and 1. Thirty percent received LT with a 1-year mortality rate of 16%, whereas for nontransplanted patients it reached 90%. Clinical features were compared according to transplant eligibility. In the univariate analysis model, lung failure (HR, 3.01; 95% CI, 1.48-6.09; P = 0.002), high lactate levels (HR, 1.03; 95% CI, 1.02-1.04; P0.001) and CLIF-ACLF score (HR, 1.04; 95% CI, 1.01-1.09; P = 0.026) were independently correlated to increased inhospital mortality. LT reduced mortality risk (HR, 0.16; 95% CI, 0.04-0.72; P = 0.016).Lung failure, CLIF-ACLF score and blood lactate levels at admission were the only statistically significant independent predictors of inhospital mortality, more accurate in determining transplant success than ACLF grade.

Adeno-associated virus (AAV) gene therapies are highly promising, such as the onasemnogene abeparvovec (Zolgensma) in spinal muscle atrophy (SMA). We report the first case of fatal systemic thrombotic microangiopathy (TMA) following onasemnogene abeparvovec in a 6-month-old child with SMA type 1, carrying a potential genetic predisposition in the complement factor I gene. Other cases of TMA have recently been reported after onasemnogene abeparvovec and after AAV9 minidystrophin therapy in Duchenne muscular dystrophy. The risk-benefit ratio of this therapy must therefore be assessed. Early recognition of TMA and targeted immunotherapy are fundamental to ensure the safety of patients treated with AAV gene therapies.

Introduction: Lichen planus is an inflammatory condition that can affect the vulva and vagina. Although more common in women over 50 years of age, lichen planus can affect younger women and complicate pregnancy. During pregnancy, lichen planus can cause vaginal irritation, antepartum bleeding, and postpartum hemorrhages. It is imperative to maintain good control of the disease during pregnancy with topical corticosteroids. Case Report: A 35-year-old female with a history of vaginal lichen planus, on vaginal hydrocortisone, presented to the labor and delivery ward in the active stage of labor. She proceeds with a vaginal delivery that is followed by a postpartum hemorrhage requiring a blood transfusion. The postpartum hemorrhage was secondary to bleeding from the vaginal mucosa that was intolerant to sutures. Bleeding was then controlled with topical hemostatic agents as well as vaginal packing. Conclusion: Uncontrolled vaginal lichen planus can be associated with postpartum hemorrhage at the time of delivery. Some providers may recommend a cesarean section to prevent these outcomes; however, instead it is recommended to focus on adequate control of the disease prior to delivery and to proceed with a vaginal delivery. Standard regimens of topical corticosteroids can be safe and effective at preventing flares of lichen planus in pregnancy. In the event of a postpartum hemorrhage secondary to lichen planus, topical hemostatic agents and vaginal packing should be implemented as means to minimize blood loss.

INTRODUCTION: Stiff Person Syndrome (SPS) is a rare neurological disorder, first described in 1956 by Moersch and Woltman. The clinical picture has an insidious onset of classic findings of episodic painful spasms, hyperreflexia, axial muscle stiffness, progressing slowly to the proximal limb muscles. Painful hyperlordosis due to lumbar spine stiffness is a diagnostic characteristic of SPS. CASE REPORT: Male, 69 years old, with SPS for 40 years, referred by the neurologist to the spine surgeon because of failure to conservative management of chronic low back pain, progressively acute leg and gait impairment. Physical examination is difficult to perform in SPS because it triggers spasms. MRI presented zygoapophyseal joint, intervertebral discs and muscle degeneration, including a L4L5 cranial migrated herniated disc. Once there were no other effective ways to manage his axial and radicular pain, it was decided to perform percutaneous transforaminal endoscopic discectomy for L4L5 decompression, L3 to S1 dorsal ganglion root medial branch ablative radiofrequency rhizotomy to relieve facet pain and L2 dorsal sensory ganglion pulsed radiofrequency rhizotomy for modulation of chronic low back pain. One year postoperative follow up, the patient has showed improvement in the VAS and SF-36. CONCLUSION: Chronic pain reported by a patient must be addressed in the biological, psychological and social dimensions. Understanding the multidimensionality of the factors involved with pain allows planning less aggressive and highly efficient strategies in uncommon and off label patients, as in the case of SPS.