Retrograde tubing as a rescue treatment for megaoesophagus: a case report.

Familial dysautonomia (FD) is a genetic disease of the autonomous and sensory nervous systems. Severe gastro-oesophageal reflux is common and one of the major complications. Some patients with FD develop megaoesophagus. Oesophageal malfunction, accompanied by oesophageal food and secretion retention, results in recurrent aspiration and other severe respiratory complications. Through a traditional case report, we wish to show how reverse tubing of the oesophagus can lead to significant symptomatic improvement in these patients. Moreover, this technique can serve as an alternative treatment for other oesophageal motility disorders.

A fully 3D-printed versatile tumor-on-a-chip allows multi-drug screening and correlation with clinical outcomes for personalized medicine.

Optimal clinical outcomes in cancer treatments could be achieved through the development of reliable, precise ex vivo tumor models that function as drug screening platforms for patient-targeted therapies. Microfluidic tumor-on-chip technology is emerging as a preferred tool since it enables the complex set-ups and recapitulation of the physiologically relevant physical microenvironment of tumors. In order to overcome the common hindrances encountered while using this technology, a fully 3D-printed device was developed that sustains patient-derived multicellular spheroids long enough to conduct multiple drug screening tests. This tool is both cost effective and possesses four necessary characteristics of effective microfluidic devices: transparency, biocompatibility, versatility, and sample accessibility. Compelling correlations which demonstrate a clinical proof of concept were found after testing and comparing different chemotherapies on tumor spheroids, derived from ten patients, to their clinical outcomes. This platform offers a potential solution for personalized medicine by functioning as a predictive drug-performance tool.

Rapid Classification of Sarcomas Using Methylation Fingerprint: A Pilot Study.

Sarcoma classification is challenging and can lead to treatment delays. Previous studies used DNA aberrations and machine-learning classifiers based on methylation profiles for diagnosis. We aimed to classify sarcomas by analyzing methylation signatures obtained from low-coverage whole-genome sequencing, which also identifies copy-number alterations. DNA was extracted from 23 suspected sarcoma samples and sequenced on an Oxford Nanopore sequencer. The methylation-based classifier, applied in the nanoDx pipeline, was customized using a reference set based on processed Illumina-based methylation data. Classification analysis utilized the Random Forest algorithm and t-distributed stochastic neighbor embedding, while copy-number alterations were detected using a designated R package. Out of the 23 samples encompassing a restricted range of sarcoma types, 20 were successfully sequenced, but two did not contain tumor tissue, according to the pathologist. Among the 18 tumor samples, 14 were classified as reported in the pathology results. Four classifications were discordant with the pathological report, with one compatible and three showing discrepancies. Improving tissue handling, DNA extraction methods, and detecting point mutations and translocations could enhance accuracy. We envision that rapid, accurate, point-of-care sarcoma classification using nanopore sequencing could be achieved through additional validation in a diverse tumor cohort and the integration of methylation-based classification and other DNA aberrations.

Giant inguinal hernia repair using standard transverse inguinal incision with mesh. A retrospective case control study.

BACKGROUND: Giant inguinal hernia (GIH) is a rare condition in the developed world, and the literature is scarce. Case reports describe different techniques in an attempt to prevent abdominal compartment syndrome (ACS). We aimed to review our experience with GIH repair. METHOD: A retrospective review of the medical records of all consecutive patients who underwent a tension-free mesh GIH repair using a transverse inguinal incision between 2014 and 2021 at a tertiary university referral center. In brief, the technique included head-down positioning, maximal pre-incision reduction of hernia contents, and repair with mesh. Follow-up was conducted in outpatient clinic. We compared the results to a time-based open standard inguinal hernia repair group (control group). RESULTS: During the study period, 58 patients underwent an open GIH repair with mesh without abdominal preparation. 232 patients were included in the control group. The mean surgery duration was 125.5 min in the GIH group and 84 min in the control group (p < 0.001). Bowel resection was not necessary in any case. In-hospital complication rates were 13.8% vs. 5.6% in the GIH and control groups, respectively (p = 0.045). Early complication rates (up to 30 days post-operatively) were 62.1% vs. 14.7% in the GIH and control groups, respectively (p < 0.001). Late complications rate was similar (p = 0.476). ACS and mortality were not reported. No recurrence event was reported in the GIH group. CONCLUSION: Tension-free mesh repair for GIH using a standard transverse inguinal incision is feasible and safe and there is no need for abdominal cavity preparation. Early complications are more common than in the control group, but there were no higher rate of late or severe complications and no recurrence event.

Effect of Magnetic Resonance Imaging on Acute Surgical Treatment of Pregnant Patients: A Single Institution Study.

BACKGROUND: Abdominal pathology in pregnant patients is a frequent challenge for emergency department physicians. Ultrasound is the imaging modality of choice but is inconclusive in approximately one-third of cases. Magnetic resonance imaging (MRI) is becoming increasingly available, even in acute settings. Multiple studies have defined the sensitivity and specificity of MRI in this population. OBJECTIVES: To evaluate the use of MRI findings in pregnant patients presenting with acute abdominal complaints to the emergency department. METHODS: This retrospective cohort study was conducted at a single institution. Data were collected on pregnant patients who underwent an MRI for acute abdominal complaints between 2010 and 2019 at a university center. Patient demographics, diagnosis at admission, ultrasound and MRI findings, and discharge diagnosis were recorded and evaluated. RESULTS: In total, 203 pregnant patients underwent an MRI for acute abdominal complaints during the study period. MRI was found without pathology in 138 cases (68%). In 65 cases (32%), the MRI showed findings that could explain the patient's clinical presentation. Patients presenting with long-standing abdominal pain (> 24 hours), fever, leukocytosis, or elevated C-reactive protein values were at a significantly increased risk of having an acute pathology. In 46 patients (22.6%), MRI findings changed the primary diagnosis and management while in 45 patients (22.1%) MRI findings improved characterization of the suspected pathology. CONCLUSIONS: MRI is helpful when clinical and sonographic findings are inconclusive, leading to changes in patient management in more than one-fifth of patients.

Feasibility and safety of a novel blunt tip concealed needle device for pericardial access in porcine models.

BACKGROUND: Percutaneous pericardial access is the cornerstone of various procedures in clinical cardiology. The two commonly used methods utilizing large bore (LB) and smaller micropuncture (MP) needles often lead to inadvertent RV punctures. As both of these techniques push the pericardium inward, the novel blunt tip concealed needle device (BTCND) introduces the concept of bringing a small portion of the pericardium into a tube, where needle puncture and guidewire can be passed into the pericardial space all within the safety of the tube. METHODS: The BTCND (Via One®, CardioVia, Nazareth, Israel) is a tool designed to allow for safe percutaneous subxiphoid pericardial access. In this preclinical study, a total of 18 procedures were performed in 5 female pigs. All procedures were performed under general anesthesia and under fluoroscopic guidance with a team of veterinarians and cardiac electrophysiologists. A laparoscopic camera was used to demonstrate and record the procedure. The Institutional Animal Care and Use Committees approved all preclinical experiments. RESULTS: A total of 18 procedures were performed on five female pigs. In all procedures, the physicians safely introduced guidewire into the pericardial space. Device operation was not associated with any adverse events or bleeding, nor was any damage seen to the pericardium, the heart, or other organs during the procedure. CONCLUSION: The result of our preclinical report demonstrates that the device is intuitive, easy to use, and effective for its intended use. Large preclinical studies are needed to validate the results of the study.

Pneumatosis Cystoides Coli Presenting as Acute Abdomen in a Patient with Complicated Behcet's Disease: A Case Report.

BACKGROUND Behcet's disease (BD) is defined as vasculitis involving arteries and veins of any size and affecting almost any organ system. Abdominal manifestations of BD are diverse and nonspecific. Mucosal ulcerations can be seen in the gastrointestinal tract. Extensive ulcerations, especially ileocecal lesions, can lead to perforation, strictures, fistulas, and abscesses. Pneumatosis cystoides intestinale is a rare benign condition characterized by multiple submucosal or subserosal, gas-filled cysts in the gastrointestinal tract wall. Pneumatosis cystoides coli (PCC) affects the colon, can present with a wide range of manifestations, and can mimic many different systemic diseases. We describe a case of PCC in a patient with Behcet's disease who presented to the Emergency Department with a clinical suspicion of acute abdomen. CASE REPORT A 40-year-old man with complicated Behcet's disease, treated with high-dose steroids, presented with acute abdomen and CT scan findings highly suggestive of intestinal obstruction due to ileocolic intussusception. He underwent laparoscopic right hemicolectomy. Pathology demonstrated PCC disease. CONCLUSIONS Pneumatosis cystoides coli can present with a broad range of symptoms and can be secondary to many systemic and autoimmune diseases. With radiological evidence and a high level of suspicion, unnecessary surgery can be prevented.

Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study.

OBJECTIVE: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). BACKGROUND: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative. METHODS: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression. RESULTS: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25). CONCLUSIONS: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

Mortality in relation to presence and type of oral antithrombotic agent among adult trauma patients: a single-center retrospective cohort study.

PURPOSE: Oral anticoagulants (AC) and antiplatelet (AP) agents are increasingly prescribed to prevent and treat acute and chronic thrombotic conditions. The direct oral anticoagulants (DOAC), a newer class of AC, raise concerns in the trauma setting. Our study aims to compare the mortality rates and other outcomes among adult trauma patients based on pre-admission AC/AP status. METHODS: We conducted a retrospective cohort study of a prospectively collected database of trauma patients previously on DOAC, warfarin, aspirin or clopidogrel. A matched control group of trauma patients not receiving AC/AP was used for comparison. Our primary endpoint was in-hospital mortality according to antithrombotic medication class. Secondary endpoints included length of stay (LOS), intensive care unit (ICU) admission, need for blood transfusion, and discharge to a dependent setting. Univariate and multivariate analyses were conducted. RESULTS: There were 996 exposed patients and 234 controls, with no major clinically significant difference among study groups in terms of gender, injury site, injury severity, mechanism, and comorbidities. The mortality rates were 2.14% (control, 5/234), 2.88% (DOAC, 3/104), 3.34% (aspirin, 17/509), 7.63% (warfarin, 18/236), 9% (clopidogrel, 8/89), and 13.79% (aspirin + clopidogrel, 8/58) (p < 0.001). In multivariate analyses, there was no difference regarding mortality between DOAC and reference groups. Blood transfusion was more likely in patients receiving warfarin or AP than those prescribed DOAC. CONCLUSION: There was no evidence of increased mortality or blood transfusion requirement among trauma patients on DOAC, including head trauma patients. Further studies on head trauma and specific subgroups of DOAC are recommended.

Senolytic elimination of Cox2-expressing senescent cells inhibits the growth of premalignant pancreatic lesions.

OBJECTIVE: Cellular senescence limits tumourigenesis by blocking the proliferation of premalignant cells. Additionally, however, senescent cells can exert paracrine effects influencing tumour growth. Senescent cells are present in premalignant pancreatic intraepithelial neoplasia (PanIN) lesions, yet their effects on the disease are poorly characterised. It is currently unknown whether senolytic drugs, aimed at eliminating senescent cells from lesions, could be beneficial in blocking tumour development. DESIGN: To uncover the functions of senescent cells and their potential contribution to early pancreatic tumourigenesis, we isolated and characterised senescent cells from PanINs formed in a Kras-driven mouse model, and tested the consequences of their targeted elimination through senolytic treatment. RESULTS: We found that senescent PanIN cells exert a tumour-promoting effect through expression of a proinflammatory signature that includes high Cox2 levels. Senolytic treatment with the Bcl2-family inhibitor ABT-737 eliminated Cox2-expressing senescent cells, and an intermittent short-duration treatment course dramatically reduced PanIN development and progression to pancreatic ductal adenocarcinoma. CONCLUSIONS: These findings reveal that senescent PanIN cells support tumour growth and progression, and provide a first indication that elimination of senescent cells may be effective as preventive therapy for the progression of precancerous lesions.

Circumferential esophageal replacement by a decellularized esophageal matrix in a porcine model.

BACKGROUND: Tissue engineering is an attractive alternative to conventional esophageal replacement techniques using intra-abdominal organs which are associated with a substantial morbidity. The objective was to evaluate the feasibility of esophageal replacement by an allogenic decellularized esophagus in a porcine model. Secondary objectives were to evaluate the benefit of decellularized esophagus recellularization with autologous bone marrow mesenchymal stromal cells and omental maturation of the decellularized esophagus. METHODS: Eighteen pigs divided into 4 experimental groups according to mesenchymal stromal cells recellularization and omental maturation underwent a 5-cm long circumferential replacement of the thoracic esophagus. Turbo green florescent protein labelling was used for in vivo mesenchymal stromal cells tracking. The graft area was covered by a stent for 3 months. Clinical and histologic outcomes were analyzed over a 6-month period. RESULTS: The median follow-up was 112 days [5; 205]. Two animals died during the first postoperative month, 2 experienced an anastomotic leakage, 13 experienced a graft area stenosis following stent migration of which 3 were sacrificed as initially planned after successful endoscopic treatment. The stent could be removed in 2 animals: the graft area showed a continuous mucosa without stenosis. After 3 months, the graft area showed a tissue specific regeneration with a mature epithelium and muscular cells. Clinical and histologic results were similar across experimental groups. CONCLUSION: Circumferential esophageal replacement by a decellularized esophagus was feasible and allowed tissue remodeling toward an esophageal phenotype. We could not demonstrate any benefit provided by the omental maturation of the decellularized esophagus nor its recellularization with mesenchymal stromal cells.

International workshop on "professionalism in the practice of medicine- where are we now?"

Medical professionalism refers to attributes, values, behaviors, responsibilities and commitments of physicians that are congruent with the public's expectations. An international workshop on medical professionalism took place at the Dead Sea, Israel, on December 11-12, 2016. The meeting brought together local medical professionals, physicians and others, as well as international experts, to discuss definitions of professionalism and wrestle with current challenges facing the profession including its perceived status and physician satisfaction, unprofessional behavior and its relation to health care quality and patient safety, and professionalism as a learned competence. Individual medical schools reported on educational efforts to promote professionalism in their curricula. Patient complaints as an improvement mechanism were explored on a national and health plan level. I was found that complaints regarding physician behavior are rare in the Israeli context and need to be dealt with expeditiously at a local level in order to be effective tools for change. The meeting provided a venue to understand local and international strategies and mechanism for regulation and self-regulation, highlighting the role of the Israel Medical Association. A major focus of the meeting was on intergenerational differences in attitude and practice and the necessary adaptation of medicine to the digital age. We provide an overview of the topics addressed, synopsis, evaluation and lessons learned in this first-ever national meeting on medical professionalism in Israel.

Involvement of CCR6/CCL20/IL-17 axis in NSCLC disease progression.

OBJECTIVES: Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. METHODS: A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. RESULTS: CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52-15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. CONCLUSION: Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations.