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Cholelithiasis is the most common biliary tract disorder. Surgery is the treatment of choice for symptomatic gallstones. Aims of this study were to investigate the feasibility and short-term safety of a new endoscopic procedure with a specially designed Nitinol gallbladder stent for blockage of gallstone migration, the Shai™ Stent. The Shai stent is designed to enable free bile flow, which will be supposed to prevent recurrent attacks. The Shai™ Stent was inserted into the gallbladder during a standard ERCP procedure using a conventional metal stent delivery system. The aim of the present study was to investigate the feasibility and safety of insertion and deployment and removal of the stent into the gallbladder of pigs. In addition, the short-term safety of the stent was evaluated. Fifteen stents were placed in the gallbladder of 15 pigs. Mean procedure time was 25 min (15–37). The maximum follow-up before sacrifice was 42 days. The stent in 1 pig had migrated at the 42 days follow-up but there were no macroscopic changes in its gallbladder or other organs. The stent remained in place in the remaining 12 pigs at autopsy, and the gallbladder and bile ducts were macroscopically normal. Stent removal was easily done in two pigs immediately after placement. Correct placement and removal of the Shai™ Stent in the gallbladder is safe and feasible in pigs. Further clinical trials are warranted to confirm these results and to effectively evaluate the capability of this stent as an innovative biotechnology to block gallstones from migration and impaction.

Acute kidney injury (AKI) is a highly fatal complication of malaria. We used the Kidney Disease Improving Global Outcomes (KDIGO) and Pediatric Risk, Injury, Failure, Loss, End-Stage Kidney Disease (pRIFLE) guidelines to assess AKI among children. One hundred children with Plasmodium falciparum malaria were recruited from the St. Andrew's Catholic Hospital. Admission and 48-h serum creatinine were estimated. Weight and height of the participants were measured, and AKI status determined with the KDIGO and pRIFLE guidelines. A questionnaire was used to collect the socio-demographic and clinical data of participants. Two percent and 5% of the participants had AKI according to the KDIGO and pRIFLE criteria, respectively. Per the KDIGO guidelines, 1% of the participants had Stage 2 and 1% also had Stage 3 AKI. Four percent had Stage 1 (risk) and 1% had Stage 2 (injury) AKI per the pRIFLE criteria. Participants with AKI were dehydrated, and neither had sepsis or on antibiotics when the KDIGO guideline was used. Participants who had AKI were dehydrated, with 80% having sepsis and 40% on antibiotics when the pRIFLE criteria were used. There was no association between the KDIGO and pRIFLE criteria with respect to AKI status of participants (k = -0.029, P = 0.743). Two percent and 5% of the study participants had AKI when the KDIGO and pRIFLE guidelines were used respectively. One percent of the participants had Stage 2 and 1% also had Stage 3 AKI per KDIGO; 4% had Stage 1 (risk) and 1% had Stage 2 (injury) AKI per the pRIFLE.

Background Influenza vaccination is recommended by the World Health Organization for high risk groups, yet few data exist on influenza disease burden in West Africa. Methods We estimated medically attended influenza-associated illness rates among residents of Shai-Osudoku and Ningo Pram-Pram Districts (SONPD), Ghana. From May 2013 to April 2015, we conducted prospective surveillance for severe acute respiratory illness (SARI) and influenza-like illness (ILI) in 17 health facilities. In 2015, we conducted a retrospective assessment at an additional 18 health facilities to capture all SONPD SARI and ILI patients during the study period. We applied positivity rates to those not tested to estimate total influenza cases. Results Of 612 SARI patients tested, 58 (9%) were positive for influenza. The estimated incidence of influenza-associated SARI was 30 per 100,000 persons (95% CI: 13-84). Children aged 0 to 4 years had the highest influenza-associated SARI incidence (135 per 100,000 persons, 95% CI: 120-152) and adults aged 25 to 44 years had the lowest (3 per 100,000 persons, 95% CI: 1-7) (p

Working with Teenage Parents: Handbook of Theory and Practice for Practitioners Working with Pregnant Teenagers, Young Parents and Their Children By J. Raphael-Leff, N. Malberg, D. Shai, M. Mills, E. Hopper, M. Zaphirious Woods, Anna Freud Centre, 2011, £15.00, pb, 258 pp. ISBN: 9780954931933

Robert N Jamison,1 Robert R Edwards,1 Samantha Curran,1 Limeng Wan,1 Edgar L Ross,1 Christopher J Gilligan,1 Shai N Gozani2 1Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School, Brigham & Women’s Hospital, Chestnut Hill, MA, USA; 2NeuroMetrix, Inc., Woburn, MA, USACorrespondence: Shai N GozaniNeuroMetrix, Inc., 4b Gill St., Woburn, MA, 01801, USATel +1 781 314 2789Fax +1 781 890 1556Email gozani@neurometrix.comPurpose: Fibromyalgia is a chronic condition characterized by widespread pain and interference with daily activities. The aim of this study is to assess the benefit of transcutaneous electrical nerve stimulation (TENS) for persons diagnosed with fibromyalgia.Patients and Methods: Adults meeting diagnostic criteria for fibromyalgia were randomized in a double-blind trial to receive either an active (n=62) or sham (n=57) wearable TENS device for 3-months. Subjects were classified as having lower or higher pain sensitivity by Quantitative Sensory Testing (QST). Patient Global Impression of Change (PGIC, primary outcome) and secondary efficacy measures including Fibromyalgia Impact Questionnaire (FIQR), Brief Pain Inventory (BPI) and painDETECT questionnaire (PDQ) were assessed at baseline, 6-weeks and 3-months. Treatment effects were determined by a mixed model for repeated measures (MMRM) analysis of the intention-to-treat (ITT) population (N=119). A pre-specified subgroup analysis of pain sensitivity was conducted using an interaction term in the model.Results: No differences were found between active and sham treatment on PGIC scores at 3-months (0.34, 95% CI [− 0.37, 1.04], p=0.351) in the ITT population. However, in subjects with higher pain sensitivity (n=60), PGIC was significantly greater for active treatment compared to sham (1.19, 95% CI [0.24, 2.13], p=0.014). FIQR total score (− 7.47, 95% CI [− 12.46, − 2.48], p=0.003), FIQR pain item (− 0.62, 95% CI [− 1.17, − 0.06], p=0.029), BPI Interference (− 0.70, 95% CI [− 1.30, − 0.11], p=0.021) and PDQ (− 1.69, 95% CI [− 3.20, − 0.18], p=0.028) exhibited significant improvements for active treatment compared to sham in the ITT population. Analgesics use was stable and comparable in both groups.Conclusion: This study demonstrated modest treatment effects of reduced disease impact, pain and functional impairment from wearable TENS in individuals with fibromyalgia. Subjects with higher pain sensitivity exhibited larger treatment effects than those with lower pain sensitivity. Wearable TENS may be a safe treatment option for people with fibromyalgia.Clinicaltrials.gov Registration: NCT03714425.Keywords: fibromyalgia, wearable, transcutaneous electrical nerve stimulation, neuromodulation, non-pharmacological treatment, clinical trial

Background: It has been suggested that fellowship training can reduce patient morbidity and mortality related to the learning curve. There are limited data comparing the outcomes before and after b...

Background: Auricular keloids belong to the most perplexing medical conditions, which have significant psychosocial impact on the patient’s body image and quality of life. Summary: The article is purposed to provide dermatologists and plastic surgeons with the best proven practice using intralesional cryosurgery for the treatment of the different auricular keloid types in order to obtain superior clinical results by minimizing the probability of recurrence. In the past 20 years, the authors have developed novel procedures in order to increase the effectiveness of intralesional cryosurgery on auricular keloids, including hydrodissection, warm gauze technique, and excision of dangling skin. Long-lasting clinical results with a low recurrence rate and a satisfactory aesthetic outcome are achieved with no deformation of the ear framework.

Background Adherence to direct oral anticoagulants (DOACs) remains a concern among non‐valvular atrial fibrillation (AF) patients. We aimed to assess patterns of adherence with DOACs and examine their association with ischemic stroke and systemic embolism (SE). Methods This retrospective cohort study includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed non‐valvular AF between January 2014 and March 2019, who initiated DOACs within 90 days of AF diagnosis and used DOACs exclusively. Adherence was assessed using the proportion of days covered (PDC) over the first year of treatment, and high adherence was defined as PDC ≥80%. Regression models were used to identify predictors of high adherence to DOACs and to examine the association between adherence and stroke or SE. Results Overall 15,255 patients were included in this study. The proportion of highly adherent (PDC ≥80%) DOACs users was around 75% and decreased slightly over the years. On multivariable analyses, the likelihood of high adherence to DOACs increased with age and across higher socioeconomic classes, and was more likely among females, Jews, statins users, and patients with CHA2DS2‐VASc score ≥2. Risk of stroke and SE was lower among highly adherent DOACs users; adjusted HR 0.56 (95% CI, 0.45–0.71), compared to users with PDC

BACKGROUND & AIMS There is a lack of convenient, sensitive, non-invasive strategies for screening and surveillance for colorectal neoplasia. An assay combining the results of circulating gastrointestinal epithelial cells (CEC) and somatic mutations of cell-free DNA adjusting for age/sex using a unique algorithm is evaluated in patients requiring colonoscopy. METHODS A prospective single-site 458-subject study (asymptomatic: 43% screening/43% surveillance, enriched with 65 symptomatic subjects) undergoing colonoscopy was conducted. The test analyzed CEC and somatic mutations. The probability of advanced neoplasia (advanced adenoma (AA) and CRC) was determined by logistic regression methods adjusted for expected CRC incidence rate, prior history of AA, patient age and sex on a training subset. A linear predictor was developed to generate a score scaled from 0-100. The test performance was evaluated on an independent set of subjects using pre-specified algorithms and cutpoint. RESULTS Based on a pre-defined clinical threshold and predictive model derived from the training set (n=232), analysis of an independent asymptomatic validation set (n=194) yielded 89% (Lower exact one-sided 95% CI: 80%) specificity and 100% (95% CI: 37%)/78% (95% CI: 61%) sensitivity for detection of CRC/AA. In a secondary analysis, excluding surveillance subjects, the 97-subject screening cohort yielded 91% (95% CI: 79%) specificity and CRC/AA sensitivity at 100% (95% CI:37%)/83% (95% CI: 56%, 87% for advanced neoplasia 95% CI: 64%). Significant associations, (p CONCLUSIONS A multimodal blood test that included CEC and somatic mutations with adjustment for age and sex demonstrated high sensitivity for the diagnosis of advanced colorectal neoplasia. The resulting score captures prognostic information for CRC progression of index adenoma size and number and has the potential to enable stratification of patients for screening or post- polypectomy surveillance colonoscopy.

AML can be associated with autoimmune or inflammatory phenomena (AIP) occurring prior, concomitantly, or after its diagnosis. Trisomy 8 is one of the most common cytogenetic abnormalities associated with AML. We describe three patients with AML, trisomy 8, and associated AIP and review the known literature on this association. All of our patients had major symptomatic relief when treated with leukemia-directed therapy and corticosteroids. AIP in AML may be an underdiagnosed phenomenon, particularly in patients with trisomy 8.

Endoscopic findings in early esophageal cancer are often subtle and require careful inspection and meticulous endoscopic examination. When dysplasia is suspected, we recommend performing 1 or 2 targeted biopsies of the abnormal area and review with a pathologist specialized in evaluating gastrointestinal diseases. In the case of adenocarcinoma, after resection of any visible cancer, residual Barrett's can be treated by ablation. Endoscopic resection can offer the opportunity for patients to avoid surgery. Further studies are needed to evaluate the optimal management of circumferential and near-circumferential lesions as well as tools and techniques to facilitate the performance of endoscopic submucosal dissection and endoscopic mucosal resection.

We report a case of huge carcinosarcoma of lung initially presenting as an intra-abdominal mass: treatment with enucleation of the firm sarcomatous component followed by pulmonary resection. A 65-year-old man with mild mental retardation who smoked one pack of cigarettes per day until 1-month before he was admitted to our hospital complaining of a progressively poorer appetite, vomiting and an abdominal mass at the left upper quadrant region. Physical examination revealed a palpable mass over the left upper abdomen with percussion dullness of the lower hemithorax. Chest radiograph revealed a homogeneous mass lesion in the left lower lung field with obliteration of the costophrenic angle. Computed tomography scans of the chest disclosed a huge mass over the left lower thorax and upper abdomen with compression of the heart and shift of the esophagus and descending aorta to the midline. Sono-guided aspiration biopsy cytology revealed squamous cell carcinoma. Surgical intervention with enucleation of the very firm sarcomatous component with fragmentation followed by radical lobectomy. Chemotherapy was planned as adjuvant therapy in the postoperative period, but the patient's family declined it. The patient is currently survived without tumor recurrence 14 months after surgery. Our case revealed a huge tumor not only mediastinal compression but also initial presenting abdominal symptoms. Initially, from the symptoms and nonbiopsy study, we were unable to determine exactly if it was an intrathoracic tumor or an intra-abdominal tumor. This case highlights the importance of remaining clinically vigilant to differentiate an unusual tumor mass, and preoperative tissue proof is warranted.

Scarring of the face following chemical peeling is an uncommon and devastating complication. This case report describes the successful treatment of bulky mature keloids on both cheeks following deep chemical peeling by using a combined approach of intralesional cryosurgery followed by pulsed dye and ablative fractional CO2 laser therapy. Level of evidence: Level V, therapeutic study.

While perforations, postoperative fistulas, and leaks have traditionally led to surgical or interventional radiology consultation for management, the introduction of the over-the-scope clip has allowed increased therapeutic possibilities for endoscopists. While primarily limited to case reports and series, the over-the-scope clip successfully manages gastrointestinal bleeding, perforations, as well as postoperative leaks and fistulas. Retrospective studies have demonstrated a relatively high success rate and a low complication rate. Given the similarity to variceal banding equipment, the learning curve with the over-the-scope clip is rapid. However, given the higher risk of procedures involving the use of the over-the-scope clip, it is essential to obtain the scope in a stable position and grasp sufficient tissue with the cap using a grasping tool and/or suction. From our experience, while closure may be successful in lesions sized up to 3 cm, successful outcomes are obtained for lesions sized

Background COVID-19, the novel coronavirus, has caused a global pandemic affecting millions of people around the world. Risk factors for critical disease in adults are advanced age and underlying medical comorbidities, including cancer. Data are sparse on the effect of COVID-19 infection on pediatric patients with cancer during their active antineoplastic therapy. The optimal management of antineoplastic treatment during COVID-19 infection in this unique population is controversial. Aim To describe the severity and clinical course of COVID-19 infection in pediatric patients with cancer during active antineoplastic treatment and to study their course of treatment. Methods Clinical and laboratory data were collected from medical files of patients diagnosed with COVID-19, confirmed by polymerase chain reaction (PCR), who received active antineoplastic treatment between March 2020 and May 2021 in a large tertiary pediatric medical center. Results Eighteen patients with diverse pediatric cancers are described. They were infected with COVID-19 at different stages of their antineoplastic treatment regimen. Eight had an asymptomatic COVID-19 infection, nine had mild symptoms, and one had severe disease. All of them recovered from COVID-19 infection. Two patients experienced delays in their antineoplastic treatment; none of the other patients had delays or interruptions, including patients who were symptomatic for COVID-19. Conclusion In pediatric patients with cancer who test positive for COVID-19, yet are asymptomatic or have mild symptoms, the continuance of antineoplastic therapy may be considered.

Purpose To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. Methods Injection index is defined as the mean anti-vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: ≥9, low: Results Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04-12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. Conclusion Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.

Background: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI. Methods: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments. Results: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P =0.02; odds ratio, 0.58 (95% CI, 0.37–0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment. Conclusions: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897). Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02610283.

BACKGROUND: Temporal lobe T2 hyperintensity has been described in association with prenatal cytomegalovirus (CMV) infection on fetal MRI. However, these findings are often perplexing with high inter-observer variability. Our objective was to evaluate temporal lobe T2 signal quantitatively in prenatal CMV infection. METHODS: In this retrospective study, 119 fetuses, of which 51 fetuses with suspected CMV exposure (29–36 weeks of gestation) based on maternal seroconversion and age-matched 68 normal controls, were included. Mean and maximal temporal lobe T2 signal were evaluated quantitatively by measuring the T2 signal in the temporal lobes relative to the amniotic fluid’s signal. Intra-observer, inter-observer variability and diagnostic performance were assessed. The occurrence of neonatal sensorineural hearing loss (SNHL) was recorded. RESULTS: Relative temporal lobe T2 signal did not change along with the examined gestational age. Of our suspected CMV cohort, 29 fetuses were positive for fetal CMV infection on polymerase chain reaction (PCR) analysis. There were no statistically significant differences in the relative mean or maximal temporal lobes T2 signal between CMV positive, CMV negative fetuses, or normal controls. No correlation was found between neonatal SNHL and temporal lobe T2 signal. CONCLUSIONS: When temporal lobe T2 signal is analyzed quantitatively, CMV infected fetuses do not present an increased signal than age-matched controls. Thus, reported subjective temporal T2 hyperintensities should be interpreted carefully and should have a limited effect on pregnancy management, especially as an isolated finding. Our study illustrates the importance of quantitative imaging in diagnostic neuroradiology.

Acute chorioamnionitis complicates 1-2% of all pregnancies and might increase the prevalence of endometritis that can cause Asherman syndrome or adhesions, but little is known about the direct effects of chorioamnionitis on future fertility. We aimed to evaluate the effect of chorioamnionitis on future fertility and obstetrics complications in patients diagnosed with chorioamnionitis during their pregnancy. We performed an observational, case-control retrospective study of pregnant women aged 18-40 years old, hospitalized with a diagnosis of chorioamnionitis between January 2013 and December 2017. The control group consisted of patients with similar demographic/obstetrics characteristics, matched with a ratio of 1:2 without chorioamnionitis. The prevalence of post gestational diagnostic hysteroscopy was significantly higher in the study group as compared to the control group (22.9% versus 9.0%, respectively

Third trimester amniocentesis is often performed when indications arise after 24 weeks of gestation—typically to investigate new sonographic findings, and might be related to pre-term birth. Scarcity of data exists concerning the risks of third-trimester amniocentesis in twin pregnancies. A retrospective cohort study of all twin gestations that underwent amniocentesis in a tertiary hospital between 2007 and 2016. Outcomes and procedure-related complications were compared between third-trimester (≥ 24 weeks) and mid-trimester amniocentesis (16–23 weeks). Primary outcome was defined as membrane rupture within four weeks of procedure. Logistic regression analysis was utilized to adjust results to potential confounders. Overall, 185 eligible women were included, of them, 28 (15.1%) underwent third-trimester amniocentesis and 157 (84.9%) underwent mid-trimester amniocentesis. Women in the third-trimester amniocentesis group were younger and presented higher frequencies of intra-uterine growth restriction (31.5 vs. 35.3, p

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by multiorgan hamartomas, including cerebral lesions, with seizures as a common presentation. Most TSC patients will also experience neurocognitive comorbidities. Our objective was to use machine learning techniques incorporating clinical and imaging data to predict the occurrence of major neurocognitive disorders and seizures in TSC patients. A cohort of TSC patients were enrolled in this retrospective study. Clinical data included genetic, demographic, and seizure characteristics. Imaging parameters included the number, characteristics, and location of cortical tubers and the presence of subependymal nodules, SEGAs, and cerebellar tubers. A random forest machine learning scheme was used to predict seizures and neurodevelopmental delay or intellectual developmental disability. Prediction ability was assessed by the area-under-the-curve of receiver-operating-characteristics (AUC-ROC) of ten-fold cross-validation training set and an independent validation set. The study population included 77 patients, 55% male (17.1 ± 11.7 years old). The model achieved AUC-ROC of 0.72 ± 0.1 and 0.68 in the training and internal validation datasets, respectively, for predicting neurocognitive comorbidity. Performance was limited in predicting seizures (AUC-ROC of 0.54 ± 0.19 and 0.71 in the training and internal validation datasets, respectively). The integration of seizure characteristics into the model improved the prediction of neurocognitive comorbidity with AUC-ROC of 0.84 ± 0.07 and 0.75 in the training and internal validation datasets, respectively. This proof of concept study shows that it is possible to achieve a reasonable prediction of major neurocognitive morbidity in TSC patients using structural brain imaging and machine learning techniques. These tools can help clinicians identify subgroups of TSC patients with an increased risk of developing neurocognitive comorbidities.

Vascular dysfunction is entwined with aging and in the pathogenesis of Alzheimer's disease (AD) and contributes to reduced cerebral blood flow (CBF) and consequently, hypoxia. Hyperbaric oxygen therapy (HBOT) is in clinical use for a wide range of medical conditions. In the current study, we exposed 5XFAD mice, a well-studied AD model that presents impaired cognitive abilities, to HBOT and then investigated the therapeutical effects using two-photon live animal imaging, behavioral tasks, and biochemical and histological analysis. HBOT increased arteriolar luminal diameter and elevated CBF, thus contributing to reduced hypoxia. Furthermore, HBOT reduced amyloid burden by reducing the volume of pre-existing plaques and attenuating the formation of new ones. This was associated with changes in amyloid precursor protein processing, elevated degradation and clearance of Aß protein and improved behavior of 5XFAD mice. Hence, our findings are consistent with the effects of HBOT being mediated partially through a persistent structural change in blood vessels that reduces brain hypoxia. Motivated by these findings, we exposed elderly patients with significant memory loss at baseline to HBOT and observed an increase in CBF and improvement in cognitive performances. This study demonstrates HBOT efficacy in hypoxia-related neurological conditions, particularly in AD and aging.

An “unplanned excision” refers to soft tissue sarcomas excised without planning imaging studies and a diagnostic biopsy, resulting in the presence of residual disease and usually necessitating a re-excision procedure. We aimed to assess the impact of previous unplanned excisions on the intra-operative pathologic assessment at the time of re-excision, in terms of need to perform repeat assessments and the accuracy to predict margin status of the final pathologic specimen. Data was collected for all patients with extremity soft tissue sarcoma who had undergone wide local excision limb salvage surgery or amputation between 2012 and 2017. Intra-operative pathologic assessment with frozen sections was performed in all cases and was classified as negative, negative but close (

ObjectiveAnti-drug antibodies (ADA) to anti-tumour necrosis factor (anti-TNF) therapy drive treatment loss of response. An association between intestinal microbial composition and response to anti-TNF therapy was noted. We therefore aimed to assess the implications of antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD).DesignWe analysed data from the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all patients with IBD in Israel. We included all patients treated with anti-TNF who had available ADA levels. Survival analysis with drug use as time varying covariates were used to assess the association between antibiotic use and ADA development. Next, specific pathogen and germ-free C57BL mice were treated with respective antibiotics and challenged with infliximab. ADA were assessed after 14 days.ResultsAmong 1946 eligible patients, with a median follow-up of 651 days from initiation of therapy, 363 had positive ADA. Cox proportional hazard model demonstrated an increased risk of ADA development in patients who used cephalosporins (HR=1.97, 95% CI 1.58 to 2.44), or penicillins with β-lactamase inhibitors (penicillin-BLI, HR=1.4, 95% CI 1.13 to 1.74), whereas a reduced risk was noted in patients treated with macrolides (HR=0.38, 95% CI 0.16 to 0.86) or fluoroquinolones (HR=0.20, 95% CI 0.12 to 0.35). In mice exposed to infliximab, significantly increased ADA production was observed in cephalosporin as compared with macrolide pretreated mice. Germ-free mice produced no ADA.ConclusionADA production is associated with the microbial composition. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillin-BLIs, or by treatment with fluoroquinolones or macrolides.

Objectives There are multiple etiologies of heterotopic ossification )HO) and limited information regarding the outcome of HO complicating specific injuries in children. The aim of this study was to examine the characteristics and long term results of treatment of HO in pediatric patients with severe traumatic brain injury (TBI). Patients and methods The files of all patients treated at a pediatric rehabilitation center with severe TBI during the study period were retrospectively examined. Patients diagnosed with HO during the rehabilitation period were examined in the clinic. Results Of 75 patient with TBI, HO was diagnosed in six patients at an average of four months after the injury. No difference was found between patients with or without HO, regarding age, gender, GCS, length of stay in rehabilitation facility or ventilation during this period. In all the six patients diagnosed with HO, the involved side was the spastic and paraparetic limb, 4 in the elbow, 1 knee and 1 hip joint. Symptoms resolved in five patients with NSAIDS treatment. One patient required surgical excision of the elbow HO, due to a progressive ulnar neuropathy. Conclusion Severe TBI in children may be complicated by HO of the spastic and paraparetic limb at a rate of 8%, the majority in the elbow joint. The rate and manifestations of the HO are less severe than in adults. Although treatment and timing of excision of HO is controversial, a peripheral neuropathy may be an indication for early excision of the HO mass. [Hand Microsurg 2021; 10(2.000): 80-87]

Late onset neutropenia (LON) after rituximab is a previously described complication. We aimed to assess and characterize LON after obinutuzumab, a novel anti-CD20 antibody, in the real-world setting and compare it to LON after rituximab therapy. We retrospectively analyzed 330 consecutive patients with lymphoproliferative neoplasms (rituximab-treated n = 283; obinutuzumab-treated n = 47). LON occurred in 23% patients with similar incidence in rituximab (n = 66, 23%) or obinutuzumab (n = 10, 21%) groups (p = 0.853). Patients treated for CLL and post-transplantation lymphoproliferative disease (PTLD) were at higher risk to develop LON (multivariate analysis: HR for CLL - 6.62 CI 95% 1.33-32.92; HR for PTLD 15.82 CI 95% 2.04-122.4). Febrile neutropenia was uncommon during LON and occurred in 15 patients (4.5%; rituximab (n = 14) and obinutuzumab (n = 1).These data suggest that LON after obinutuzumab treatment is as common as with rituximab. The similarities in LON after rituximab and obinutuzumab argue for a possible class effect for anti-CD20 monoclonal antibodies.

BACKGROUND Minimally-invasive endoscopic strip-craniectomy (or suturectomy) for the repair of craniosynostosis combined with postoperative cranial orthotic molding has been widely adopted in the past 2 decades, proving itself as a safe and effective procedure. Over time the authors transitioned from performing an endoscopic strip-craniectomy, to performing the same surgery without the endoscope. The authors here describe our technique and compare its results to those published in the literature for endoscopic suturectomies. METHODS A retrospective chart review was performed for patients with nonsyndromic craniosynostosis who underwent minimally-invasive nonendoscopic suturectomy between 2019 and 2020 at our institution. RESULTS Thirteen patients (11 males; 2 females) were operated including 5 Metopic, 5 Sagittal, 2 coronal, and 1 lambdoid craniosynostosis. The average age at surgery was 4.35 months. The average length of surgery was 71 minutes. Averaged intraoperative estimated blood loss was 31.54 mL. Eleven patients received a blood transfusion (most before performing the skin incision) with a mean amount of 94.62 mL of blood transfused during surgery. The mean hemoglobin at discharge was 10.38 mg/dL. There was only 1 intraoperative mild complication. The mean intrahospital length of stay was 1.77 days with no postoperative complications noted. All patients initiated remodeling orthotic treatment following surgery. Long-term follow-up scans were available for 8 patients (5 metopic, 2 sagittal, and 1 lambdoid) with an average follow-up of 9 months. In all cases, there was a significant improvement in the skull width at the synostosis location as well as in the skull proportions and symmetry. The above outcomes are similar to those published in the literature for endoscope-assisted strip-craniectomies. CONCLUSIONS Suturectomies assisted with cranial orthosis remodeling for the treatment of all types of nonsyndromic craniosynostosis can be performed without an endoscope while maintaining minimal-invasiveness, good surgical results, and low complication rates.

Background/aim Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk. Materials and methods MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples. Results MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index. Conclusion Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

To investigate the effect of the COVID-19 pandemic on healthcare utilization related to labor and delivery and to assess the effect of the COVID-19 pandemic on intra-partum and delivery complications.This retrospective study was performed at a university-affiliated, tertiary medical center. It included women admitted to the delivery room from 1 March 2020 to 23 July 2020 during the first wave of the COVID-19 pandemic. They were compared against women who were admitted to the delivery room during the same time period in 2019. The outcomes of 2701 deliveries during the pre-pandemic period were compared to those of 2668 deliveries during the pandemic period. Main outcomes were pregnancy and delivery outcomes.The mean number of emergency department visits before admission for delivery was higher in the pre-pandemic period than in the pandemic period (2.3 ± 1.5 and 2.1 ± 1.3 visits, respectively;In our study population, in the presence of public and accessible obstetric medicine, the first wave of the COVID-19 pandemic did not affect pregnancy or early delivery outcomes.

PURPOSE To evaluate whether ethnicity affects the risk of full mutation expansion among females heterozygous for FMR1 premutation. METHODS Women who carry the FMR1 premutation alelle of Jewish origin who underwent fragile X prenatal diagnosis between 2011 and 2018 in two medical centers in Israel were included. The heterozygote women and fetuses were analyzed for the number of CGG repeats and AGG interruptions. RESULTS Seven hundred sixty-six subjects were included. Parental ethnicity was fully concordant in 592 cases (Jewish, Ashkenazi, and non-Ashkenazi). Ashkenazi compared with non-Ashkenazi heterozygotes have a significantly higher mean number of CGG repeats (68 ± 8.7, 64 ± 6.4 respectively, P = 0.03) and a lower mean number of AGG interruptions (0.89 ± 0.83, 1.60 ± 1.18 respectively, p = 0.0001). Overall, 56/198 (28.2%) fetuses of Ashkenazi heterozygotes had an expansion to a full mutation compared with 6/98 among the non-Ashkenazi (6.1%) (p = 0.001). Multivariate analysis demonstrated that, in addition to CGG repeats and AGG interruptions (which contributed 68.3% of variance), ethnicity is an independent risk factor for a full mutation expansion (odds ratio [OR] = 2.04, p

Background Substance misuse is a global public health problem. In addition to social and economic concerns, consumption of tobacco and alcohol is associated with susceptibility to cardiovascular, respiratory, and infectious diseases, cancers, and risk of transition to substance use disorders. African data suggest regional differences in the prevalence and patterns of substance use, but a number of key questions remain. This cross-sectional population-based study of middle-aged adults aims to examine prevalence and socio-demographic correlates of substance use in four sub-Saharan African countries, in rural and urban settings. Methods Participants aged between 40 and 60 years were recruited from six research centres as part of the Africa Wits-INDEPTH partnership for Genomic Research study. Data on patterns of tobacco and alcohol consumption was captured, and the latter further assessed using the CAGE (cut-annoyed-guilty-eye) questionnaire. Results Data from 10,703 participants suggested that more men (68.4%) than women (33.3%) were current substance users. The prevalence of current smoking was significantly higher in men than in women (34.5% vs 2.1%, p Conclusions Regional variation in the patterns and prevalence of substance use was observed across study sites, and in rural and urban settings. The high levels of substance use recorded in this study are of concern due to the increased risk of associated morbidities. Further longitudinal data will be valuable in determining trends in substance misuse in Africa.

AIMS Oral anticoagulants (OACs) are considered the mainstay in preventing stroke in atrial fibrillation (AF). OAC treatment remains suboptimal among AF patients, even after the introduction of direct oral anticoagulants (DOACs). We aimed to assess trends overtime and current implementation of OAC treatment guidelines in AF, using a large dataset of real world data from Israel. METHODS This is a retrospective cohort study that includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed nonvalvular AF between January 2014 and December 2019 with CHA2 DS2 -VASc score ≥2. OAC treatment rates were calculated and multivariate regression models were used to identify predictors of OACs initiation. RESULTS Overall, 46 531 patients were included in the study. The 3-months cumulative OAC treatment rates increased consistently over the years: 46.9% (95% confidence interval, 46.1-47.7%), 54.9% (54.1-55.6%) and 61.7% (60.9-62.4%) during 2014-2015, 2016-2017 and 2018-2019, respectively. DOACs constituted 51.3% of prescribed OACs in 2014-2015 and increased to 95.1% during 2018-2019. On multivariate analyses, the likelihood of OACs initiation among AF patients increased across the years and across higher socioeconomic classes, and was more likely among females, Jews, statins users and patients previously screened for colorectal cancer, but less likely among smokers and patients with impaired renal function. The likelihood of treatment increased with higher CHA2 DS2 -VASc score and decreased with higher HAS-BLED score. CONCLUSION Despite the increasing OAC treatment rates among high-risk AF patients, mainly attributed to the expanding DOAC use, OAC treatment scope is still far from optimal.

BACKGROUND AND AIMS In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF. METHODS For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA-), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays. RESULTS At baseline, participants (92% men; body mass index = 30.2 kg/m2 ) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P

Background We tested whether CHA2DS2-VASc and/or HAS-BLED scores better predict ischemic stroke and major bleeding, respectively, than their individual components in maintenance hemodialysis (MHD) patients with atrial fibrillation (AF). Methods A retrospective cohort study of a clinical database containing the medical records of 268 MHD patients with non-valvular AF (167 women, mean age 73.4 ± 10.2 years). During the median follow-up of 21.0 (interquartile range, 5.0–44.0) months, 46 (17.2%) ischemic strokes and 24 (9.0%) major bleeding events were reported. Results Although CHA2DS2-VASc predicted ischemic stroke risk in the study population (adjusted HR 1.74 with 95% CI 1.23–2.46 for each unit of increase in CHA2DS2-VASc score, and HR of 5.57 with 95% CI 1.88–16.49 for CHA2DS2-VASc score ≥ 6), prior ischemic strokes/transient ischemic attacks (TIAs) were non-inferior in both univariate and multivariate analyses (adjusted HR 8.65 with 95% CI 2.82–26.49). The ROC AUC was larger for the prior ischemic stroke/TIA than for CHA2DS2-VASc. Furthermore, the CHA2DS2-VASc score did not predict future ischemic stroke risks in study participants who did not previously experience ischemic strokes/TIAs (adjusted HR 1.41, 95% CI: 0.84–2.36). The HAS-BLED score and its components did not have predictive abilities in discriminating bleeding risk in the study population. Conclusions Previous ischemic strokes are non-inferior for predicting of future ischemic strokes than the complete CHA2DS2-VASc score in MHD patients. CHA2DS2VASc scores are less predictive in MHD patients without histories of CVA/TIA. HAS-BLED scores do not predict major bleeding in MHD patients. These findings should redesign approaches to ischemic stroke risk stratification in MHD patients if future large-scale epidemiological studies confirm them.

Background/aims Cold snare polypectomy (CSP) is an effective method of polyp removal for small colorectal polyps. However, the effect of submucosal injection in cold snare endoscopic mucosal resection (CS-EMR) for small polyps is unclear. Therefore, this study aimed to evaluate the effect of submucosal injection in CS-EMR for small polyps. Methods Between 2018 and 2019, 100 consecutive small colorectal polyps (5-10 mm) were identified in 58 patients. The first 50 consecutive polyps were removed by CS-EMR, and the remaining 50 were removed by CSP. Demographic data, clinical data, endoscopic findings, procedure times, complication rates, and pathology data were collected. Results No difference in the complete resection rate was observed between the CS-EMR and CSP groups. A total of 9 polyps showed post-polypectomy bleeding (7 had immediate bleeding, 1 had delayed bleeding, and 1 had both immediate and delayed bleeding). No difference in the bleeding rate was observed between the two groups. In multivariate analysis, warfarin (odds ratio [OR], 42.334; 95% confidence interval [CI], 1.006-1,781.758) and direct-acting oral anticoagulants (OR, 35.244; 95% CI, 3.853-322.397) showed a significantly increased risk of bleeding. Conclusions The effect of submucosal injection in CSP was not significant for small colorectal polyps.

To evaluate the outcome of a novel, combined endoscopic and mini-open repair (CEMR) of a chronic complete retracted proximal hamstring tendon avulsion (PHA). A retrospective case series of a single-surgeon database for all patients, with a minimum of 1-year follow-up, who underwent CEMR between July 2015 and September 2019 was performed. Patients were evaluated for their functional outcome using the Perth Hamstring Assessment Tool (PHAT). At the latest follow-up, patients were evaluated for their muscle strength, subjective satisfaction and post-operative complications. Twelve patients who underwent endoscopic surgery for chronic PHA were identified, of which seven patients underwent CEMR. After exclusion of one patient from the study due to an open claim for health insurance, six patients (five males) with a mean age of 48 years (range 20–61 years) were evaluated. The mean time from injury to surgery was 12 months (range 2–43 months). At a mean follow-up of 28 months (range 12–55 months), the average PHAT score was 73 (range 70–80). The mean subjective activity level percentage improved from 34 (range 20–50) pre-surgery to 81 (range 75–90) post-surgery. The mean strength of the quadriceps, hamstring at 30°, and hamstring at 90° of the operated leg compared to the uninjured leg did not differ significantly. One patient underwent adhesiolysis 1 year after the index procedure for treatment of subcutaneous adhesions. CEMR is a viable and safe option for the treatment of chronic complete proximal hamstring tears, with good to excellent short-term functional outcome. Level of evidence: IV.

Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with transient and permanent forms. Currently, there are no effective tools to predict severity and time to resolution in infants with transient hyperinsulinism (tHI). Therefore, our objective was to assess whether early glucose trends predict disease duration in tHI. Methods A retrospective, pilot cohort of infants admitted with tHI was phenotyped for clinical and laboratory parameters. Blood glucose (BG) values were collected from the first documented hypoglycemia for 120 h (five days). Results In 27 neonates with tHI, the presence of fetal distress (p=0.001) and higher mean daily BG (p=0.035) were associated with shorter time to resolution of hypoglycemia. In a further sensitivity analysis that grouped the cohort by the presence or absence of fetal distress, we found that in neonates without fetal distress, lower mean daily glucose was associated with longer disease duration (R2=0.53, p=0.01). Conclusions Our pilot data suggests that predictors for disease duration of tHI may be elicited in the first week of life, and that tHI associated with fetal distress may represent a distinct clinical entity with a shorter time course.

Previous studies have reported a longitudinal association between cybervictimization and suicidal thoughts and behavior. However, the relationship between cyber-perpetration and prospective suicide risk remains unclear. The sample was composed of 2150 at-risk adolescents (mean age 15.42), enrolled in Vocational Education and Training high schools in Israel. Cyberbullying, traditional bullying, depression, hostility, serious suicidal ideations, and suicide attempts were assessed through self-report questionnaires at the beginning of the school year and one year later. All types of victimization and preparation were cross-sectionally associated with suicide ideation and attempts. Longitudinal associations were found between cyber-perpetration and suicidal ideation/attempts. Cyber-perpetrators were found to be over twice more likely to report serious suicidal ideation (OR = 2.04) or attempt suicide (OR = 2.64) in the subsequent year compared to noninvolved adolescents. These associations were significant even after adjusting for baseline depression, hostility, and traditional bullying. Traditional bullying perpetration was prospectively associated with suicide attempts. Traditional victimization was cross-sectionally associated with suicide ideation and attempts but not prospectively. Cybervictimization was prospectively associated with suicide ideation but not to suicide attempts. The findings demonstrate the prospective risk of involvement in bullying in regard to suicide ideation and behavior. Cyberbullying was found to be a somewhat differentiated phenomena from traditional bullying.

Background Chemotherapy improves overall survival after surgery and radiotherapy for newly diagnosed high-risk IDH-mutant low-grade gliomas (LGGs), but a proportion of patients treated with temozolomide (TMZ) will develop recurrent tumors with TMZ-induced hypermutation. We aimed to determine the prevalence of TMZ-induced hypermutation at recurrence and prognostic implications. Methods We sequenced recurrent tumors from 82 patients with initially low-grade IDH-mutant gliomas who underwent reoperation and correlated hypermutation status with grade at recurrence and subsequent clinical outcomes. Results Hypermutation was associated with high-grade disease at the time of reoperation (OR 12.0 95% CI 2.5-115.5, P = .002) and was identified at transformation in 57% of recurrent LGGs previously exposed to TMZ. After anaplastic (grade III) transformation, hypermutation was associated with shorter survival on univariate and multivariate analysis (HR 3.4, 95% CI 1.2-9.9, P = .024), controlling for tumor grade, subtype, age, and prior radiotherapy. The effect of hypermutation on survival after transformation was validated in an independent, published dataset. Hypermutated (HM) tumors were more likely to develop discontiguous foci of disease in the brain and spine (P = .003). To estimate the overall incidence of high-grade transformation among low-grade IDH-mutant tumors, data from a phase II trial of TMZ for LGG were analyzed. Eight-year transformation-free survival was 53.8% (95% CI 42.8-69.2), and 61% of analyzed transformed cases were HM. Conclusions TMZ-induced hypermutation is a common event in transformed LGG previously treated with TMZ and is associated with worse prognosis and development of discontiguous disease after recurrence. These findings impact tumor classification at recurrence, prognostication, and clinical trial design.

Shigella remains in the top four pathogens responsible for moderate to severe diarrhoea in children below 5 years of age. The shigella O-specific polysaccharide (O-SP) is a promising vaccine target. We developed a conjugate vaccine prototype incorporating a unique well defined synthetic oligosaccharide hapten, chemically designed for optimal antigenic, conformational, structural, and functional mimicry of the O-SP from Shigella flexneri 2a (SF2a). We aimed to assess the safety, tolerability, and immunogenicity of this original synthetic oligosaccharide-based vaccine candidate, SF2a-TT15, conceived to drive the antibody response towards the key protective determinants of the native lipopolysaccharide antigen, in a first-in-human phase 1 study.We did a first-in-human, dose-escalating, single-blind, observer-masked, randomised, placebo-controlled study at the Clinical Research Center of Tel Aviv Sourasky Medical Center (Israel). Participants were healthy adults aged 18-45 years with low titres of serum SF2a-specific IgG antibodies. 64 eligible participants were assigned to one of two cohorts. 32 participants in each of the two cohorts were randomly assigned via computer-generated algorithm in a stepwise manner to receive the 2 μg (cohort 1) and 10 μg oligosaccharide dose (cohort 2) of the SF2a-TT15 vaccine candidate non-adjuvanted or adjuvanted with aluminium hydroxide (alum) or matching placebos. The vaccine was administered as three single intramuscular injections into the arm, 28 days apart. The primary outcome was the incidence and severity of adverse events, which were assessed in the intention-to-treat safety population analysis including all participants who were randomly assigned and received at least one vaccine or placebo injection. The immunogenicity endpoints were secondary outcomes and were analysed in all participants who were randomly assigned, received all of the assigned injections before the time of the immunogenicity assessment, and provided blood samples for immunological follow-up (per-protocol immunogenicity analysis). The study is registered with ClinicalStudies.gov, NCT02797236 and is completed.Of 203 volunteers initially screened, 64 participants were enrolled between Sept 20, 2016, and Sept 26, 2017. In each of the two cohorts, 12 participants received the adjuvanted vaccine, 12 received the non-adjuvanted vaccine and eight received the matching placebo (four each). The SF2a-TT15 glycoconjugate was well tolerated at both doses. No serious or severe adverse events occurred. Overall, seven (88%) of eight to 12 (100%) of 12 in each group of volunteers had one adverse event or more after receiving the study agents with the majority of adverse events, 300 (98%) of 307, considered mild in intensity. Of the seven adverse events defined as moderate in severity, one (nausea) was suspected to be related to the vaccine candidate. At all post-immunisation days and for both oligosaccharide doses, whether adjuvanted or not, SF2a-TT15 induced significantly higher serum IgG anti-SF2a lipopolysaccharide geometric mean titres (GMTs) as compared with baseline or with the corresponding GMTs in placebo recipients (p0·01). After one injection, the non-adjuvanted 10 μg oligosaccharide dose induced a 27-times increase in IgG GMT (5080 vs 189) and the non-adjuvanted 2 μg oligosaccharide dose induced a five-times increase (1411 vs 283), compared with baseline. Alum enhanced the specific IgG response at 2 μg oligosaccharide dose after the third injection (GMTs 3200 vs 1176, p=0.045).SF2a-TT15 was safe and well tolerated and induced high titres of anti-SF2a LPS IgG antibodies. These results support further evaluation of this original synthetic oligosaccharide-protein conjugate vaccine candidate for safety, immunogenicity, and protective efficacy in target populations.The European Union Seventh Framework Programme.

Background and aims: The prevalence of coronavirus disease 2019 (COVID-19) resulted in health anxiety among general population and unreasonable referring to health centers. This study aimed to assess health anxiety related to COVID-19 in individuals referring to healthcare centers of Arak, Iran in 2020. Methods: Using convenient sampling method, the participants of this cross-sectional study were selected from 16 urban health centers of Arak. Salkovskis 18-item Health Anxiety Inventory (HAI-18) was completed by 392 participants. The collected data entered in SPSS software version 24 and was analyzed by Mann-Whitney U and Kruskal-Wallis tests. Results: Mean ± SD of total score of health anxiety was 28.96 ± 7.62. Most participants (74.7%) had medium anxiety and 19.1% had high anxiety. The mean of total score of health anxiety was higher in the 30-59 age range, higher education, single people and students. Participants with chronic diseases and symptoms of cold and people who referred to health centers due to COVID-19 screening had a higher anxiety level. Conclusion: Most people referring to health centers of arak had moderate anxiety. COVID-19-related health anxiety was higher in middle age range, higher education, students, people with chronic diseases, and people with symptoms of common cold.

INTRODUCTION In primary Crohn's disease (CD), laparoscopic ileocolic resection has been shown to be both feasible and safe, and is associated with improved outcomes in terms of postoperative morbidity and length of hospital stay. However, it is unclear whether the laparoscopic approach can be routinely proposed as a safe procedure for patients with complex enterovisceral fistulas.The aim of this study is to assess the feasibility and safety of laparoscopic surgery for complex enterovisceral fistulas, and compare it with CD patients who underwent primary laparoscopic ileocolic resection. PATIENTS AND METHODS All patients who underwent laparoscopic primary ileocolic resection (LICR) for complex enterovisceral fistulas between July 2006 and July 2017 were included. They were compared with all consecutive patients who underwent LICR for nonfistulizing CD in the same period of time. Patients with previous bowel resections or recurrent disease were excluded. RESULTS Nineteen patients with 20 enterovisceral fistulas (group I) were compared with 61 patients who underwent LICR for nonfistulizing disease (group II). There were no differences between the groups in age, sex, preoperative body mass index, nutritional status, and American Society of Anesthesiology score. There was no conversion to open surgery in both groups.There were no significant differences between groups in terms of operative time [120 (range: 65 to 232) vs. 117 (range: 62 to 217) min, P=0.7], hospital stay [6 (5 to 8) vs. 7 (5 to 65) days, P=0.56], overall morbidity 26.3% versus 16.4% (P=0.33), major morbidity (Clavien-Dindo >3) 15.7% versus 10% (P=0.66) and reoperation rates 5.3% versus 4.9% (P=0.9). There was no mortality in both groups. CONCLUSIONS Our experience shows that the laparoscopic approach for complex enterovisceral fistulas in selected CD patients is both feasible and safe in the hands of experienced inflammatory bowel disease surgeons with extensive expertise in laparoscopic surgery. Larger study cohorts are needed to confirm these findings.

Introduction There is no consensus regarding the optimal device for displaced intracapsular hip fractures. This retrospective study compared two techniques (1) cannulated cancellous screw (CCS), and (2) Targon Femoral Neck (TFN) plate. Materials and methods Data regarding gender, operational data, complications, pain, Quality of life and function scores were retrieved. Results 103 patients were included, 42 were treated using CCS, compared to 61 treated using TFN. Operative time shorter for CCS (p = 0.019). Complication rates were not different (p > 0.05). Conclusion As CCS method take shorter operating time and reduced costs, CCS should be used for the treatment of displaced ICHF.

BACKGROUND The use of electric scooters (e-scooters) has dramatically increased as they become an attractive alternative for public transportation in busy metropolitan areas worldwide. Despite their benefits, e-scooters challenge the health-care system with poorly understood forms of injuries, mainly orthopaedic fractures. To our knowledge, this study is the first to investigate e-scooter-related orthopaedic fracture patterns, mechanisms of injury, and management. METHODS Data on 3,331 e-scooter-related admissions were retrospectively collected between May 2017 and February 2020 in a level-I trauma center. These admissions were analyzed for demographic variables, orthopaedic fracture diagnosis (using the AO/OTA classification), associated injuries, and surgical treatment. RESULTS During the study period, a total of 716 fractures were diagnosed in 563 patients, with 46.4% of the patients requiring hospitalization. Of 492 upper-limb fractures, 89.2% occurred in a rider fall mechanism; and of 210 lower-limb fractures, 15.7% occurred in rider-vehicle collisions. Fifty-nine percent of long bone fractures were complex fragmentary and/or intra-articular fractures. Orthopaedic surgeons recommended that 225 fractures undergo surgical treatment. The most common upper-limb fracture was AO/OTA class 2R1A, with open reduction and internal fixation of the distal part of the radius being the most common upper-limb procedure (n = 58). The most common lower-limb fracture was AO/OTA class 41C, with open reduction and internal fixation of the proximal part of the tibia being the most common procedure (n = 28). A total of 22 patients (3.9%) required reoperation within 1 year. CONCLUSIONS This investigation provides unique information on demographic characteristics, patterns, and treatment of orthopaedic fractures secondary to the high-energy mechanism of e-scooter injuries. These new in-depth data are important, first, for health-care system preparedness with regard to management and resource allocation to treat these challenging injuries and, second, for legislators promoting safety and injury prevention strategies.

Following hyperacute management after traumatic brain injury (TBI), most patients receive treatment which is inadequate or inappropriate, and delayed. This results in suboptimal rehabilitation outcome and avoidable detrimental chronic effects on patients’ recovery. This worsens long-term disability, and magnifies costs to the individual and society. We believe that accurate diagnosis (at the level of pathology, impairment and function) of the causes of disability is a prerequisite for appropriate care and for accessing effective rehabilitation. An expert-led, integrated care pathway is needed to deliver accurate and timely diagnosis and optimal treatment at all stages during a TBI patient’s care. We propose the introduction of a specialist interdisciplinary traumatic brain injury team, led by a neurosciences-trained brain injury consultant. This team would engage acutely and for a longer term after TBI to provide accurate diagnoses, which guides subsequent management and rehabilitation. This approach would also encourage more efficient collaboration between research and the clinic. We propose that the current major trauma network is leveraged to introduce and evaluate this proposal. Improvements to patient outcomes through this approach would lead to reduced personal, societal and economic impact of TBI.

Background: The prognosis of patients with non-small cell lung cancer (NSCLC) is traditionally determined by anatomic staging using the Tumor, Node, Metastasis (TNM) staging system. TNM staging neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying NSCLC patients at increased risk of recurrence after curative-intent surgery remains an important unmet need as adjuvant therapies are available that may reduce the risk of recurrence and improve patient survival. Methods: Digital Display Precision Predictor (DDPP), based on differential RNA expression in tumor versus normal tissue, was used to interrogate gene sets to determine their association with disease-free survival (DFS) in patients with non-small cell lung cancer (NSCLC) who underwent curative-intent surgery. Findings: Low versus high DDPP score was significantly associated with shorter DFS (highest recurrence risk): HR=1.88, 95% CI [1.2-2.9] (p=0.006) in all patients (n=120) and in patients with TNM stages 1-2 (p= 0.00051) (n=83). For patients with stages 1-2 and low DDPP (n=29), adjuvant chemotherapy was associated with improved DFS (p= 0.0041). High co-overexpression of CTLA-4, PD-L1 and ICOS in normal lung (28 of 120 patients), hypothesized to reflect the host immune status, was also significantly associated with decreased DFS (p= 0.0013) suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS (p=2.12E-11). Interpretation: We identified stage 1-2 NSCLC patients with high risk of recurrence who benefitted from adjuvant chemotherapy. Furthermore, identified a subset of NSCLC patients who may have poor post-surgery outcome related to an immunotolerant normal tissue profile that might be amenable to modulation by specific checkpoint blockade immunotherapies. Funding: European Union Frame Pprogram 6-funded project (Chemores FP6 Health, Grant 37 665). Declaration of Interest: Dr. Vladimir Lazar, Catherine Bresson, are full time employees of Worldwide Innovative Network (WIN) Association - WIN Consortium. Worldwide Innovative Network (WIN) Association - WIN Consortium is the owner of the patent family entitled Digital Display. The inventors are Dr. Vladimir Lazar, and Shai Magidi. Dr. Jean-Francois Martini, is a full-time employee and stockholder of Pfizer Inc. Dr. Susan Galbraith is a full-time employee and stockholder of AstraZeneca. Dr. Benjamin Solomon received honorarium for Advisory Board from AstraZeneca and Bayer. Shai Magidi receives consultancy from Worldwide Innovative Network (WIN) Association. Dr. Amir Onn receives consulting fees from Roche Israel, MSD Israel, Boehringer Ingelheim 552 and AstraZeneca. Dr. Enriqueta Felip receives advisory board and/or speaker’s bureau fee from Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-LaRoche, Glaxi Smith Kline, Janssen, Medical Trends, Medscape, Merck Sharp & Dohme, Merck Serono, Peptomyc, Peervoice, Pfizer, Puma, Regeneron, Sanofi, Springer, Syneos Health, Takeda, Touch Medical; on the board of Grifols, Independent member. Receives research funding from Fundacion Merck Salud, Grant for Oncology Innovation (GOI) EMD Serono. Dr. Josep Tabernero declares scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. Dr. Gerald Batist collaborates in formal clinical trial contracts, IITs and in joint grants funded by Canadian and Quebec governments with Roche, Merck, Novartis, Astra-Zeneca, Bayer, Esperas, Aurka, Caprion, MRM. Pr. Angel Porgador declares scientific consultancy role for PiNK Biopharma. Dr. Razelle Kurzrock has received research funding from Genentech, Merck Serono, Pfizer, Boehringer Ingelheim, TopAlliance, Takeda, Incyte, Debiopharm, Medimmune, Sequenom, Foundation Medicine, Konica Minolta, Grifols, Omniseq, and Guardant, as well as consultant and/or speaker fees and/or advisory board for X-Biotech, Neomed, Pfizer, Actuate Therapeutics, Roche, Turning Point Therapeutics, TD2/Volastra, Bicara Therapeutics, Inc., and Biological Dynamics, has an equity interest in IDbyDNA and CureMatch Inc, serves on the Board of CureMatch and CureMetrix, and is a co-founder of CureMatch. Dr. Richard L. Schilsky’s institution (ASCO) receives research grants in support of a clinical trial that he directs from the following companies: AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Genentech, Lilly, Merck, Pfizer. Dr. Schilsky reports being a consultant to Cellworks, Clarify Precision Medicine, Bryologx, EQRx and Scandion Oncology. The remaining authors declare no competing interests. Ethical Approval: The bio-banking study was approved by the IMM’s Ethics Committee.