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Facetectomy and laminectomy are techniques for decompressing lumbosacral spinal stenosis. Resections of posterior bony or ligamentous parts normally lead to a decrease in stability. The degree of instability depends on the extent of resection, the loading situation and the condition of the intervertebral discs. The correlation between these parameters is not well understood. In order to investigate how these parameters relate to one another, a three-dimensional, non-linear finite element model of the lumbosacral spine was created. Intersegmental rotations, intradiscal pressures, stresses, strains and forces in the facet joints were calculated while simulating an intact spine as well as different extents of resection (left and bilateral hemifacetectomy, hemilaminectomy and bilateral laminectomy, two-level laminectomy), disc conditions (intact and degenerated) and loading situations (pure moment loads, standing and forward bending). The results of the modelling showed that a unilateral hemifacetectomy increases intersegmental rotation for the loading situation of axial rotation. Expanding the resection to bilateral hemifacetectomy increases intersegmental rotation even more, while further resection up to a bilateral laminectomy has only a minor additional effect. Hemilaminectomy and laminectomy only differ in their effect for ventriflexion and muscle-supported forward bending. Two-level laminectomy increases the intersegmental rotation only for standing. Degenerated discs result in smaller intersegmental rotations and higher disc stresses at the respective levels. Decompression procedures affect the examined biomechanical parameters less markedly in degenerated than in intact discs. Resection of posterior bony or ligamentous elements has a stronger influence on the amount than on the distribution of stresses and deformations in a disc. It has only a minor effect on the biomechanical behaviour of the adjacent region. Spinal stability is decreased after a laminectomy for forward bending, and after a two-level laminectomy for standing. For axial rotation, spinal stability is decreased even after a hemifacetectomy. Patients should therefore avoid excessive axial rotation after such a treatment. [ABSTRACT FROM AUTHOR]

Malignant astrocytomas are among the most common brain tumours and few therapeutic options exist. It has recently been recognized that the ligand-activated nuclear receptor PPARγ can regulate cellular proliferation and induce apoptosis in different malignant cells. We report the effect of three structurally different PPARγ agonists inducing apoptosis in human (U87MG and A172) and rat (C6) glioma cells. The PPARγ agonists ciglitazone, LY171 833 and prostaglandin-J2, but not the PPARα agonist WY14643, inhibited proliferation and induced cell death. PPARγ agonist-induced cell death was characterized by DNA fragmentation and nuclear condensation, as well as inhibited by the synthetic receptor-antagonist bisphenol A diglycidyl ether (BADGE). In contrast, primary murine astrocytes were not affected by PPARγ agonist treatment. The apoptotic death in the glioma cell lines treated with PPARγ agonists was correlated with the transient up-regulation of Bax and Bad protein levels. Furthermore, inhibition of Bax expression by specific antisense oligonucleotides protected glioma cells against PPARγ-mediated apoptosis, indicating an essential role of Bax in PPARγ-induced apoptosis. However, PPARγ agonists not only induced apoptosis but also caused redifferentiation as indicated by outgrowth of long processes and expression of the redifferentiation marker N-cadherin in response to PPARγ agonists. Taken together, treatment of glioma cells with PPARγ agonists may hold therapeutic potential for the treatment of gliomas. [ABSTRACT FROM AUTHOR]

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We probe with deep level transient spectroscopy electron states in self-assembled InAs quantum dots. Two pronounced maxima are observed that we associate with emission from different quantum-dot orbital states. Fine structure clearly establishes distinct emission rates for quantum dots with one or two electrons in the s state and up to four electrons in the p-like states. In order to confirm these assignments spectra have been recorded in strong magnetic fields. The observed magnetic field dispersion of the emission energies is described with a harmonic oscillator model using an effective electron mass of m*=0.03me. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinomas or combined adeno-neuroendocrine carcinomas (MANEC) of small bowel usually have a dismal prognosis with limited systemic therapy options. This is the first description of a patient showing a germline-related BRCA1 mutated MANEC of his ileum. The tumor presented a susceptibility to a combined chemotherapy and the PARP1-inhibitor olaparib.Case Presentation: A 74-year old male patient presented with a metastasized MANEC of his ileum. Due to clinical symptoms his ileum-tumor and the single brain metastasis were removed. We verified the same pathogenic (class 5) BRCA1 mutation in different tumor locations. There was no known personal history of a previous malignant tumor. Nevertheless we identified his BRCA1 mutation as germline-related. A systemic treatment was started including Gemcitabine followed by selective internal radiotherapy (SIRT) to treat liver metastases and in the further course Capecitabine but this treatment finally failed after 9 months and all liver metastases showed progression. The treatment failure was the reason to induce an individualized therapeutic approach using combined chemotherapy of carboplatin, paclitaxel and the Poly (ADP-ribose) polymerase- (PARP)-inhibitor olaparib analogous to the treatment protocol of Oza et al. All liver metastases demonstrated with significant tumor regression after 3 months and could be removed. In his most current follow up from December 2017 (25 months after his primary diagnosis) the patient is in a very good general condition without evidence for further metastases.Conclusion: We present first evidence of a therapy susceptible germline-related BRCA1 mutation in small bowel adeno-neuroendocrine carcinoma (MANEC). Our findings offer a personalized treatment option. The germline background was unexpected in a 74-year old man with no previously known tumor burden. We should be aware of the familiar background in tumors of older patients as well. [ABSTRACT FROM AUTHOR]

The article shows that NFκB activation and TGFβ loss signatures are prominent ex vivo responses of peripheral blood mononuclear cells. It attempts to determine whether there is a global cellular response to the ex vivo system itself. The article shows a strong activation state of cells just maintained in culture.

Background: Histopathologic regression following neoadjuvant treatment (NT) of oesophageal cancer is a prognostic factor of survival, but the nodal status is not considered. Here, a score combining both to improve prediction of survival after neoadjuvant therapy is developed. Methods: Seven hundred and fifteen patients with oesophageal squamous cell (SCC) or adenocarcinoma (AC) undergoing NT and esophagectomy were analysed. Histopathologic response was classified according to percentage of vital residual tumour cells (VRTC): complete response (CR) without VRTC, major response with <10% VRTC, minor response with >10% VRTC. Nodal stage was classified as ypN0 and ypN+. Kaplan–Meier and Cox regression were used for survival analysis. Results: Survival analysis identified three groups with significantly different mortality risks: (1) low-risk group for CR (ypT0N0) with 72% 5-year overall survival (5y-OS), (2) intermediate-risk group for minor/major responders and ypN0 with 59% 5y-OS, and (3) high-risk group for minor/major responders and ypN+ with 20% 5y-OS (p < 0.001). Median survival in AC and SCC cohorts were comparable (3.8 (CI 95%: 3.1, 5.3) vs. 4.6 years (CI 95%: 3.3, not reached), p = 0.3). Conclusions: Histopathologic regression and nodal status should be combined for estimating AC and SCC prognosis. Poor survival in the high-risk group highlights need for adjuvant therapy. [ABSTRACT FROM AUTHOR]

Purpose: To determine the postoperative temporal course of the forces acting on a vertebral body replacement (VBR) for two well reproducible activities. Methods: A telemeterised VBR was implanted in five patients. It allows the measurement of six load components. Implant loads were measured in up to 28 measuring sessions for different activities, including standing and walking. Results: The postoperative temporal course of the resultant implant forces measured during standing and walking was similar in each patient, but the patterns varied strongly from patient to patient. In one patient, the forces decreased in the first year and then increased in the following 4 years. In another patient, the forces increased in the first few months and then decreased. In a third patient, the forces varied only slightly in the postoperative time. In two patients, there was a strong drop of the implant force in the first two postoperative months. The force was on average approximately 100 N or 71 % higher for walking than for standing. Conclusions: The strong force reduction in the first 2 months is most likely caused by implant subsidence, and the force reduction over a period of more than 6 months is most likely caused by fusion of the vertebrae adjacent to the VBR. The short-term force increase could be attributed to bone atrophy at the index level, and the long-term force increase could be attributed to an increase in the thoracic spine kyphosis angle. [ABSTRACT FROM AUTHOR]

Background: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer.Methods: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival.Results: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group.Conclusions: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.). [ABSTRACT FROM AUTHOR]

Bei steigenden medizinischen Kosten, aber begrenzt verfügbaren finanziellen Ressourcen lassen sich medizinische Behandlung und ökonomische Analyse nicht mehr voneinander trennen. Vor diesem Hintergrund gewinnen die Deckungsbeitrags- und Kostenträgerrechnung als Steuerungsinstrumente zunehmend an Bedeutung. Die transthorakale Ösophagektomie ist fester Bestandteil des aktuellen Behandlungskonzeptes bei Patienten mit Ösophaguskarzinom. Die Frage der vorliegenden Untersuchung war, ob durch das gegenwärtige DRG-System die transthorakale Ösophagektomie kostendeckend abgebildet ist. In diese retrospektive Studie eines High-volume-Zentrums wurden 161 konsekutive Patienten mit Ösophaguskarzinom eingeschlossen, die entsprechend der aktuellen S3-Leitlinie durch eine transthorakale Ösophagektomie chirurgisch therapiert wurden. Eine detaillierte und standardisierte Dokumentation der postoperativen Komplikationen erfolgte nach der Klassifikation von Dindo-Clavien und den Richtlinien der Esophagectomy Complications Consensus Group (ECCG). Für jeden einzelnen Patienten wurden die jeweiligen Istkosten unter Vollkostenansatz basierend auf der InEK-Kostenmatrix sowie die DRG-Gesamterlöse (DRG G03A) inklusiver aller Zusatzentgelte analysiert. Die durchschnittlichen Fallkosten der 161 untersuchten Patienten lagen bei 24.338 € (Median: 19.210 €; Range: 12.149 bis 127.376 €). Demgegenüber stand ein durchschnittlicher Erlös von 22.591 €. Für das Gesamtkollektiv lag somit der Deckungsbeitrag (DB) bei −281.330 € (Durchschnitt: −1747 €). Lediglich für Patienten mit einem unkomplizierten Verlauf (Dindo-Clavien 0) war der DB mit 2514 € geringfügig positiv. Mit steigendem Komplikationsscore wurde der DB zunehmend negativer (Dindo-Clavien I: −2878 €; Dindo-Clavien IVb: −58.543 €). In der Analyse der InEK-Kostenmatrix waren der Ärztliche Dienst (22,3 %) und die nichtmedizinische Infrastruktur (18,7 %) die wesentlichen Kostengruppen. Die leitliniengerechte chirurgische Behandlung von Patienten mit einem Ösophaguskarzinom lässt sich auch in einem High-volume-Zentrum nicht aus den alleinigen DRG-Erlösen finanzieren. [ABSTRACT FROM AUTHOR]

The occurrence of varicella zoster virus (VZV) reactivation is increased after allogeneic transplantation, whereas limited data are available for herpes zoster (HZ) after autologous SCT (ASCT). We determined the incidence and the prognostic significance of HZ and its correlation with VZV serology in 191 consecutive myeloma patients undergoing high-dose melphalan chemotherapy with ASCT. We found that VZV reactivation occurred in 57 (30%) patients, in 8.5% during induction and in 21.5% after ASCT peaking at 8 months after ASCT. Disease burden due to HZ was assessed as high or rather high in 70% of the patients. By immune fluorescence and Serion Elisa VZV IgG assessment, 90.8% of all patients had specific anti-VZV antibodies at ASCT. Lower specific antibody titers at transplantation were observed in patients with HZ after ASCT than in those without reactivation (P=0.009). Finally, OS was better in myeloma patients with HZ after ASCT compared with patients without HZ (P=0.007). Our data indicate that VZV reactivation after ASCT is a frequent event carrying a significant disease burden and it is associated with improved survival. Low levels of specific VZV antibodies at ASCT suggest increased vulnerability for VZV reactivation. [ABSTRACT FROM AUTHOR]

Purpose: After total disc replacement with a ball-and-socket joint, reduced range of motion and progression of facet joint degeneration at the index level have been described. The aim of the study was to test the hypothesis that misalignment of the vertebrae adjacent to the implant reduces range of motion and increases facet joint or capsule tensile forces. Methods: A probabilistic finite element analysis was performed using a lumbosacral spine model with an artificial disc at level L5/S1. Misalignment of the L5 vertebra, the gap size of the facet joints, the transection of the posterior longitudinal ligament, and the spinal shape were varied. The model was loaded with pure moments. Results: Misalignment of the L5 vertebra reduced the range of motion up to 2°. A 2-mm displacement of the L5 vertebra in the anterior direction already led to facet joint forces of approximately 240 N. Extension, lateral bending, and axial rotation caused maximum facet joint forces between 280 and 380 N, while flexion caused maximum forces of approximately 200 N. A 2-mm displacement in the posterior direction led to capsule forces of approximately 80 N. Additional moments increased the maximum facet capsule forces to values between 120 and 230 N. Conclusions: Misalignment of the vertebrae adjacent to an artificial disc strongly increases facet joint or capsule forces. It might, therefore, be an important reason for unsatisfactory clinical results. In an associated clinical study (Part 2), these findings are validated. [ABSTRACT FROM AUTHOR]

Diabet. Med. 28, 1249-1252 (2011) Abstract Aims To analyse the outcome of the proactive management of patients with diabetes, critical limb ischaemia and foot ulcers using percutaneous transluminal angioplasty as the only vascular procedure and adjuvant conservative surgery when indicated. Methods A retrospective study of patients with diabetes included in our database who sought a second opinion in our unit and met the following criteria: foot ulcer and critical limb ischaemia in patients for whom any proactive vascular treatment had not previously been considered by other teams. Results Twenty patients underwent endovascular procedures. Success was achieved in 19 cases (95%). No post-operative mortality (within 30 days after the procedure) was found. Additional surgery was required in eight cases (40%): one calcaneal ostectomy and seven minor amputations. The need for surgery was associated with infection ( P < 0.01). Limb salvage was sustained during a mean period of follow-up of 642 days ( sd 488) in 19 cases (95%). Healing was achieved in 14 cases (70%), four are still healing (20%), one underwent major amputation (5%) and the last one died before being healed (5%). Three patients died during follow-up (15%). Conclusions Management of patients with diabetes, foot ulcers and critical limb ischaemia by means of a proactive approach including endovascular procedures in specialized settings provides a high rate of limb salvage. This may result in lowering the number of lower limb amputations in our community. [ABSTRACT FROM AUTHOR]

Local control of hepatic metastases is a prognostic factor for survival of patients with metastatic colon cancer - results of a single center analysis B Background: b The aim was to evaluate local liver directed therapy on overall survival of patients with metastatic colon cancer. B Methods: b 320 patients were treated for either local recurrence or metastases, out of these 288 developed liver metastases, with simultaneous extrahepatic disease (63 local recurrence, 47 lung metastases, 12 bone metastases, 8 peritoneal cavity). [Extracted from the article]

A letter to the editor is presented about clonal Reed-Sternberg cells recurring in patients with Hodgkin's disease.

Competing Interests: Disclosure Information: The authors have no conflicts of interest to declare.

Introduction: Unplanned intensive care unit (ICU) admissions are associated with increased morbidity and mortality. This study uses interpretable machine learning to predict unplanned ICU admissions for initial nonoperative trauma patients admitted to non-ICU locations., Methods: TQIP (2020-2021) was queried for initial nonoperative adult patients admitted to non-ICU locations. Univariable analysis compared patients who required an unplanned ICU admission to those who did not. Using variables that could be known at hospital admission, gradient boosting machines (CatBoost, LightGBM, XGBoost) were trained on 2021 data and tested on 2020 data. SHapley Additive exPlanations (SHAP) were used for interpretation., Results: The cohort had 1,107,822 patients; 1.6% had an unplanned ICU admission. Unplanned ICU admissions were older (71 [58-80] vs. 61 [39-76] years, p < 0.01), had a higher Injury Severity Score (ISS) (9 [8-13] vs. 9 [4-10], p < 0.01), longer length of stay (11 [7-17] vs. 4 [3-6] days, p < 0.01), higher rates of all complications and most comorbidities and injuries (p < 0.05). All models had an AUC of 0.78 and an F1 score of 0.12, indicating poor performance in predicting the minority class. Mean absolute SHAP values revealed ISS (0.46), age (0.29), and absence of comorbidities (0.16) as most influential in predictions. Dependency plots showed greater SHAP values for greater ISS, age, and presence of comorbidities., Conclusions: Machine learning may outperform prior attempts at predicting the risk of unplanned ICU admissions in trauma patients while identifying unique predictors. Despite this progress, further research is needed to improve predictive performance by addressing class imbalance limitations., Competing Interests: Disclosures: The authors have no related conflicts of interest to declare., (Copyright © 2024 by the Shock Society.)

Background: The cost-to-charge ratio reflects the markup of hospital services. A lower cost-to-charge ratio indicates lower costs and/or greater charges. This study examines factors associated with cost-to-charge ratio trends to determine whether decreasing cost-to-charge ratio is associated with worse surgical outcomes., Methods: The Florida Agency for Healthcare Administration Inpatient database (2018-2020) was queried for common surgical procedures and linked to the Distressed Communities Index, RAND Corporation Hospital data, Center for Medicare Services Cost Reports, and American Hospital Association data. Only hospitals with monotonically increasing or decreasing cost-to-charge ratio were included in the study. Univariable analysis compared these hospitals. Using patient-level data, interpretable machine learning predicted cost-to-charge ratio trend while identifying influential factors., Results: The cohort had 67 hospitals (27 increasing cost-to-charge ratio and 40 decreasing cost-to-charge ratio) with 35,661 surgeries. Decreasing cost-to-charge ratio hospitals were more often proprietarily owned (78% vs 33%, P = .01) and had greater mean total charges ($134,349 ± $114,510 vs $77,185 ± $82,027, P < .01) with marginally greater mean estimated costs ($14,863 ± $12,343 vs $14,458 ± $15,440, P < .01). Patients from decreasing cost-to-charge ratio hospitals had greater rates of most comorbidities (P < .05) but no difference in mortality or overall complications. Machine-learning models revealed charges rather than clinical factors as most influential in cost-to-charge ratio trend prediction., Conclusions: Decreasing cost-to-charge ratio hospitals charge vastly more despite minimally greater estimated costs and no difference in outcomes. Although differences in case-mix existed, charges were the predominant differentiators. Patient clinical factors had far less of an impact., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We sought to determine the premium associated with a career in academic surgery, as measured by compensation normalized to the work relative value unit (wRVU)., Background: An academic surgical career embodying innovation and mentorship offers intrinsic rewards but is not well monetized. We know compensation for academic surgeons is less than their nonacademic counterparts, but the value of clinical effort, as normalized to the wRVU, between academic and nonacademic surgeons has not been well characterized. Thus, we analyzed the variations in the valuation of academic and nonacademic surgical work from 2010 to 2022., Methods: We utilized Medical Group Management Association Provider Compensation data from 2010, 2014, 2018, and 2022 to compare academic and nonacademic surgeons. We analyzed raw total cash compensation (TCC), wRVU, TCC per wRVU (TCC/wRVU), and TCC to collections (TCCtColl). We calculated collections per wRVU (Coll/wRVU). We adjusted TCC and TCCtColl for inflation using the Consumer Price Index. Linear modeling for trend analysis was performed., Results: Compared with nonacademic, academic surgeons had lower TCC (2010: $500,415.0±23,666 vs $631,515.5±23,948.2, -21%; 2022: $564,789.8±23,993.9 vs $628,247.4±15,753.2, -10%), despite higher wRVUs (2022: 9109.4±474.9 vs 8062.7±252.7) and higher Coll/wRVU (2022: 76.68±8.15 vs 71.80±6.10). Trend analysis indicated that TCC will converge in 2038 at an estimated $660,931., Conclusions: In 2022, academic surgeons had more clinical activity and superior organizational revenue capture, despite less total and normalized clinical compensation. On the basis of TCC/wRVUs, academia charges a premium of 16% over nonacademic surgery. However, trend analysis suggests that TCC will converge within the next 20 years., Competing Interests: T.Z. is currently receiving grant funding from the NIH (T32GM144274). The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The Cancer of Unknown Primary (CUP) syndrome is characterized by identifiable metastases while the primary tumor remains hidden. In recent years, various data-driven approaches have been suggested to predict the location of the primary tumor (LOP) in CUP patients promising improved diagnosis and outcome. These LOP prediction approaches use high-dimensional input data like images or genetic data. However, leveraging such data is challenging, resource-intensive and therefore a potential translational barrier. Instead of using high-dimensional data, we analyzed the LOP prediction performance of low-dimensional data from routine medical care. With our findings, we show that such low-dimensional routine clinical information suffices as input data for tree-based LOP prediction models. The best model reached a mean Accuracy of 94% and a mean Matthews correlation coefficient (MCC) score of 0.92 in 10-fold nested cross-validation (NCV) when distinguishing four types of cancer. When considering eight types of cancer, this model achieved a mean Accuracy of 85% and a mean MCC score of 0.81. This is comparable to the performance achieved by approaches using high-dimensional input data. Additionally, the distribution pattern of metastases appears to be important information in predicting the LOP., Competing Interests: SL received author and speaker royalties from Amboss GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gehrmann, Soenarto, Hidayat, Beyer, Quakulinski, Alkarkoukly, Berressem, Gundert, Butler, Grönke, Lennartz, Persigehl, Zander and Beyan.)

Introduction: Big Data has revolutionized healthcare research through the three Vs: volume, veracity, and variety. This study introduces the OnetoMap meta-data repository, a centralized inventory developed in collaboration with the University of South Florida's Department of Surgery., Methods: The repository offers extensive details about each database, including its primary purpose, available variables, and examples of high-impact research utilizing these databases. It aims to create a centralized inventory, enabling researchers to locate and link relevant datasets efficiently. Each dataset is described using standardized criteria to ensure clarity and usability, such as data type, source, collection methods, and potential linkages to other datasets.  Results: Currently, the OnetoMap repository contains descriptions of 49 datasets, with ongoing updates to include new datasets and additional data years. These datasets include a range of data types, including cross-sectional and longitudinal, gathered through claims, registries, electronic health records, and surveys. The repository is hosted on GitHub, enabling version control, collaboration, and open access. Effective search functionalities and descriptive categorization enhance the findability of datasets., Discussion: The data repository includes comprehensive records of patient health statuses, socioeconomic profiles, hospital structures, and physician practices, enabling nuanced interventions and addressing complex healthcare needs. It also promotes interdisciplinary research and accelerates novel discoveries by providing a centralized source of diverse data and facilitating collaboration among research teams., Conclusion: The OnetoMap meta-data repository represents a significant advancement in healthcare research by providing a centralized, detailed, and easily accessible repository of clinical research databases. Future directions include implementing automatic annual updates of datasets, exploring automatic dataset linkage, providing monthly updates on published research, creating a user chat space for enhanced collaboration, and developing code applets for simplified data analysis. These efforts will ensure that the repository remains current, functional, and accessible, ultimately facilitating new discoveries and insights in healthcare outcomes research., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mateussi et al.)

Introduction: Identifying contributors to lung transplant survival is vital in mitigating mortality. To enhance individualized mortality estimation and determine variable interaction, we employed a survival tree algorithm utilizing recipient and donor data., Methods: United Network Organ Sharing data (2000-2021) were queried for single and double lung transplants in adult patients. Graft survival time <7 d was excluded. Sixty preoperative and immediate postoperative factors were evaluated with stepwise logistic regression on mortality; final model variables were included in survival tree modeling. Data were split into training and testing sets and additionally validated with 10-fold cross validation. Survival tree pruning and model selection was based on Akaike information criteria and log-likelihood values. Estimated survival probabilities and log-rank pairwise comparisons between subgroups were calculated., Results: A total of 27,296 lung transplant patients (8175 single; 19,121 double lung) were included. Stepwise logistic regression yielded 47 significant variables associated with mortality. Survival tree modeling returned six significant factors: recipient age, length of stay from transplant to discharge, recipient ventilator duration post-transplant, double lung transplant, recipient reintubation post-transplant, and donor cytomegalovirus status. Eight subgroups consisting of combinations of these factors were identified with distinct Kaplan-Meier survival curves., Conclusions: Survival trees provide the ability to understand the effects and interactions of covariates on survival after lung transplantation. Individualized survival probability with this technique found that preoperative and postoperative factors influence survival after lung transplantation. Thus, preoperative patient counseling should acknowledge a degree of uncertainty given the influence of postoperative factors., (Published by Elsevier Inc.)

Background: The impact of different phases of COVID-19 infection on outcomes from acute calculous cholecystitis (ACC) is not well understood. Therefore, we examined outcomes of acute cholecystitis during the COVID-19 pandemic, comparing the effect of different treatment modalities and COVID-19 infection status. We hypothesized that patients with acute COVID-19 would have worse outcomes than COVID-negative patients, but there would be no difference between COVID-negative and COVID-recovered patients., Methods: We used 2020-2023 National COVID Cohort Collaborative data to identify adults with ACC. Treatment (antibiotics-only, cholecystostomy tube, or cholecystectomy) and COVID-19 status (negative, active, or recovered) were collected. Treatment failure of nonoperative managements was noted. Adjusted analysis using a series of generalized linear models controlled for confounders (age, sex, body mass index, Charlson comorbidity index, severity at presentation, and year) to better assess differences in outcomes among treatment groups, as well as between COVID-19 groups., Results: In total, 32,433 patients (skewed count) were included: 29,749 COVID-negative, 2112 COVID-active, and 572 (skewed count) COVID-recovered. COVID-active had higher rates of sepsis at presentation. COVID-negative more often underwent cholecystectomy. Unadjusted, COVID-active had higher 30-day mortality, 30-day complication, and longer length of stay than COVID-negative and COVID-recovered. Adjusted analysis revealed cholecystectomy carried lower odds of mortality for COVID-active and COVID-negative patients than antibiotics or cholecystostomy. COVID-recovered patients' mortality was unaffected by treatment modality. Treatment failure from antibiotics was more common for COVID-negative patients., Conclusion: Acute cholecystitis outcomes are affected by phase of COVID-19 infection and treatment modality. Cholecystectomy does not lead to worse outcomes for COVID-active and COVID-recovered patients than nonoperative treatments; thus, these patients can be considered for cholecystectomy if their physiology is not prohibitive., (Published by Elsevier Inc.)

Esophageal adenocarcinoma (EAC) is one of the deadliest tumor entities worldwide, with a 5-year survival rate of less than 25%. Unlike other tumor entities, personalized therapy options are rare, partly due to the lack of knowledge about specific subgroups. In this publication, we demonstrate a subgroup of patients with EAC in a large screening cohort of 826 patients, characterized by specific morphological and immunohistochemical features. This subgroup represents approximately 0.7% (6/826) of the total cohort. Morphological features of this subgroup show a striking clear cytoplasm of the tumour cells and the parallel existence of rare growth patterns like yolk sac-like differentiation and enteroblastic differentiation. Immunohistochemistry reveals expression of the fetal gut cell-like proteins Sal-like protein 4 (SALL4), claudin-6, and glypican 3. Interestingly, we find a correlation with alterations of SWI/SNF-complex associated genes, which are supposed to serve as tumor suppressor genes in various tumour entities. Our results suggest a possible implication of rare tumour subtypes in the WHO classification for EACs according to the classification for gastric cancer. Furthermore, claudin-6 positive tumors have shown promising efficacy of CAR T cell therapy in the recently published BNT-211-01 trial (NCT04503278). This represents a personalized therapeutic option for this tumor subtype., (© 2024. The Author(s).)