Multicenter Retrospective Cohort Study Research Articles

Gastric variceal obstruction improves the efficacy of endoscopic management of esophageal variceal bleeding in GOV type I.

Background and study aims Limited data exist regarding endoscopic obstruction of type I gastroesophageal (GOV I) in managing bleeding from esophageal varices. In this multicenter retrospective cohort study, we aimed to access the efficacy of blocking gastric varices in management of bleeding from esophageal varices in patients with GOV1. Patients and methods Cirrhotic patients experiencing bleeding from esophageal varices and having GOV I gastric varices in four centers were screened. All included patients were followed up for 180 days, or until death. Results A total of 93 cirrhotic patients with GOV I and bleeding esophageal varices were included. Among them, 58 patients underwent endoscopic cyanoacrylate injection (ECI) for gastric varices in addition to treatment for esophageal varices (EV), while the remaining 35 patients received treatment for EV only. Kaplan-Meier analysis demonstrated that the cumulative 180-day rebleeding rate was significantly lower in the ECI plus EV treatment group (7.9%) compared with the EV treatment group (30.7%) ( P = 0.0031). The cumulative incidence of 180-day mortality was 1.9% in the ECI plus EV treatment group and 23.9% in the EV treatment group ( P = 0.0010). Multivariable Cox regression analysis revealed that concomitant ECI treatment was an independent protective factor against 180-day rebleeding and overall mortality. Conclusions In conclusion, obstruction of gastric varices in addition to endoscopic treatment for bleeding from esophageal varices in patients with GOV 1 proved superior to endoscopic treatment alone for esophageal variceal bleeding.

Recurrence in Eyelid Sebaceous Carcinoma: A Multicentric Study of 418 Patients.

Local recurrence predicts dismal prognosis in eyelid sebaceous carcinoma (SC). Recurrence predictors vary across studies. Accurate recurrence estimation is essential for individualized therapy in eyelid SC. This study aims to identify recurrence predictors and develop a nomogram for personalized prediction in eyelid SC. We conducted a multicenter retrospective cohort study. Chart reviews were performed in 418 consecutive patients with eyelid SC. All patients were followed up after their initial surgery. Multivariate Cox regression was used to explore the independent predictors of recurrence. A nomogram for recurrence prediction was developed and validated with bootstrap resampling. The predictive accuracy and discriminative ability were compared with the Tumor, Node, Metastasis (TNM) staging system. Over a median of 60-month follow-up, 167 patients (40%) had local recurrence. The median time from diagnosis to recurrence was 14months. The 1-year cumulative recurrence rate was 18%. Diagnostic delay (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00-1.01, P = 0.001), orbital involvement (HR = 4.47, 95% CI = 3.04-6.58, P < 0.001), Ki67 (HR = 1.01, 95% CI = 1.00-1.02, P = 0.008) and initial surgery of Mohs micrographic surgery with intraoperative frozen section control (HR = 0.53, 95% CI = 0.35-0.80, P = 0.003) were independent influencing factors of recurrence. A nomogram integrating these four factors combined with pagetoid spread displayed satisfactory discriminative ability (C-index = 0.80-0.83; area under the curve [AUC] = 0.82-0.84), which compared favorably than TNM staging (all P < 0.05). The recurrence rate is high in eyelid SC. Early detection and primary resection with Mohs micrographic surgery are recommended in controlling recurrence. Patients with orbital involvement, high Ki67 expression, and pagetoid spread may require adjuvant measures. This nomogram offers more accurate recurrence estimates, aiding in therapeutic decision making.

Risk factors for neurosurgical intervention within 48 hours of admission for patients with mild traumatic brain injury and isolated subdural hematoma.

The objective was to identify demographic, clinical, and radiographic risk factors for neurosurgical intervention within 48 hours of admission in patients with mild traumatic brain injury and isolated subdural hematoma. The authors conducted a multicenter retrospective cohort study of all trauma patients admitted to 6 level I/II trauma centers who met the following criteria: admitted between January 1, 2016, and December 31, 2020, age ≥ 18 years, ICD-10 diagnosis code for isolated subdural hematoma, available initial head imaging, initial Glasgow Coma Scale score of 13-15, and arrival at the hospital within 48 hours of injury. Patients were excluded for skull fracture, non-subdural hematoma, and absence of neurosurgical consultation. The study outcome was neurosurgical intervention within 48 hours of hospital admission. Multivariable logistic regression with backward selection examined 30 demographic, clinical, and radiographic risk factors for neurosurgery. In total, 1333 patients were included, of whom 117 (8.8%) received a neurosurgical intervention. When only demographic and clinical variables were considered, sex, mechanism of injury, and hours from injury to initial head imaging were significant covariates (area under the receiver operating characteristic curve [AUROC] [95% CI] 0.70 [0.65-0.75]). When only radiographic risk factors were considered, only maximum hemorrhage thickness (in mm) and midline shift (in mm) were independent risk factors for the outcome (AUROC 0.95 [0.92-0.97]). When all demographic, clinical, and radiographic variables were considered together, advanced directive, Injury Severity Score, midline shift, and maximum hemorrhage thickness were identified as significant risk factors for neurosurgical intervention within 48 hours of hospital admission (AUROC 0.95 [0.94-0.97]). In the setting of mild traumatic brain injury with isolated subdural hematoma, radiographic risk factors were shown to be stronger than demographic and clinical variables in understanding future risk of neurosurgical intervention. These final radiographic risk factors should be considered in the creation of future prediction models and used to increase the efficiency of existing management guidelines.

Norovirus Management and Outcomes in a Multicenter Pediatric Kidney Transplant Population.

Norovirus is the most common cause of viral gastroenteritis. Studies in adult kidney recipients have documented significant morbidity associated with norovirus infection, but there are few studies in pediatric recipients. Multicenter retrospective cohort study of pediatric kidney transplant recipients with norovirus, confirmed by stool PCR, between January 1, 2008, and December 31, 2018. Outcomes of interest included duration of diarrhea, incidence of chronic diarrhea, management strategies, and graft function. Forty pediatric kidney transplant recipients from four centers were identified for inclusion. Median age at transplant was 5.4 years (IQR 2.2-11.2 years), and median time post-transplant was 1.9 years (IQR 0.8-3.8 years). Median diarrheal duration was 16 days (IQR 6.0-41.5 days); 15 patients (43%) had acute diarrhea, 8 (23%) had persistent, and 12 (30%) had chronic diarrhea. Twenty-one (53%) patients developed acute kidney injury. Thirty-five (88%) patients required supplemental fluids, 8 (20%) patients underwent immunosuppression reduction for a median of 22 days, 5 (13%) were treated with nitazoxanide, and 5 (13%) received oral immunoglobulin. Acute rejection was diagnosed in 3 (8%) patients within 6 months of norovirus diagnosis. We observed no sustained decline in eGFR at 12 months after diarrhea resolution (median eGFR difference: 2.8 mL/min/1.73 m2 [IQR: -17.1, 7.4]). Of the patients in the cohort, two lost their graft at 6.8 and 30.0 months after the onset of diarrhea. Norovirus is associated with significant morbidity in pediatric kidney transplant recipients. Various treatment interventions are being employed for norovirus infection. Larger studies, both observational and interventional, are needed to determine the optimal treatment.

Development and validation of a predictive scoring model for risk stratification of tuberculosis treatment interruption

BackgroundTuberculosis (TB) treatment interruption poses risks of antimicrobial resistance, potentially leading to treatment failure and mortality. Addressing the risk of early treatment interruption is crucial in tuberculosis care and management to improve treatment outcomes and curb disease transmission. ObjectivesThis study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption. MethodsA multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance. ResultsOf 2953 cases, two-thirds (1969) were assigned to the derivation cohort, and one-third (984) formed the validation cohort. Positive predictors included smoking, previously treated cases, and adverse drug reactions, while concurrent diabetes was protective. Based on the validation dataset, the model demonstrated good calibration (P = 0.143) with acceptable discriminative ability (AUC = 0.775). A cutoff score of 2.5 out of 11 achieved a sensitivity of 81 % and a specificity of 64.4 %. Risk stratification into low (0–2), medium (3–5), and high-risk (≥6) categories showed ascending interruption rates of 5.3 %, 18.1 %, and 41.3 %, respectively (P < 0.001). ConclusionThe predictive scoring model aids in risk assessment for TB treatment interruption, enabling focused monitoring and personalized intervention plans for higher-risk groups in the early treatment phase.

Development of a Software Support System for Targeted Treatment of Non-Small Cell Lung Cancer Utilizing Genetic Mutation Analysis Data

This study presents the development of a software support system aimed at improving targeted treatment outcomes in non-small cell lung cancer (NSCLC) by utilizing genetic mutation analysis data. PubMed BERT model were generated to identify tumor gene mutated features associated with gene-drug responses. Then the best classifier with highest accuracy served for the development of the support software. A multi-center retrospective cohort study was conducted to evaluate of treatment outcomes based on software support to identify and predict targeted therapeutic in NSCLC. The results demonstrated the potential of leveraging genetic mutation analysis data and AI technology to optimize treatment strategies and improve outcomes for NSCLC patients with PubMed BERT model in extracting and categorizing keywords to build the database (a Recall (sensitivity) score of 98.12%). The study revealed that among the 109 patients with EGFR mutations identified through NGS analysis, 72% showed partial responsiveness, overall response rate (ORR) was 67.0%, and the disease control rate (DCR) was 82.6%. The software support system developed in this study holds promise for enhancing personalized treatment approaches in NSCLC by leveraging genetic mutation analysis data to guide targeted therapies and improve the treatment outcome for patients.

Predictive factors for COVID-19 severity and mortality in hospitalized children

BackgroundUnderstanding the factors influencing disease progression and severity in pediatric COVID-19 cases is essential for effective management and intervention strategies. This study aimed to evaluate the discriminative ability of clinical and laboratory parameters to identify predictors of COVID-19 severity and mortality in hospitalized children.MethodsIn this multicenter retrospective cohort study, we included 468 pediatric patients with COVID-19. We developed a predictive model using their demographic, clinical, and laboratory data. The performance of the model was assessed using various metrics including sensitivity, specificity, positive predictive value rates, and receiver operating characteristics (ROC).ResultsOur findings demonstrated strong discriminatory power, with an area under the curve (AUC) of 0.818 for severity and 0.873 for mortality prediction. Key risk factors for severe COVID-19 in children include low albumin levels, elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and underlying medical conditions. Furthermore, ROC curve analysis highlights the predictive value of CRP, LDH, and albumin, with AUC values of 0.789, 0.752, and 0.758, respectively.ConclusionOur study indicates that laboratory values are valuable in predicting COVID-19 severity in children. Various factors, including CRP, LDH, and albumin levels, demonstrated statistically significant differences between patient groups, suggesting their potential as predictive markers for disease severity. Implementing predictive analyses based on these markers could aid clinicians in making informed decisions regarding patient management.

Clinical outcomes in paediatric tubulointerstitial nephritis and uveitis syndrome (TINU).

To evaluate the clinical presentation, course, and outcomes of uveitis in paediatric patients with tubulointerstitial nephritis and uveitis syndrome (TINU). Multicentric Retrospective Cohort Study 110 patients ≤21 years of age diagnosed with TINU from 10 sites across the United States and Canada. Clinical diagnosis of TINU required uveitis diagnosed by an ophthalmologist, elevated serum creatinine (SCr) and elevated urine β2-microglobulin (β2M) or abnormal urinalysis. Renal biopsy and systemic illness were not mandatory. Univariate and multivariate analysis was performed to analyse risk factors and treatment modalities. Median age was 13 years (Range (5.9-18.4); 52% male); median follow-up, 1.6 years (IQR 0.98-4.02). Uveitis was symptomatic in 90%, with bilateral anterior uveitis in 94%. Ninety-two (84%) patients required immunomodulatory treatment (IMT). Methotrexate (n = 44) and mycophenolate mofetil (n = 39) were the first agents after oral corticosteroids. 45% required addition of biologic agents (Adalimumab [n = 33], Infliximab [n = 8]). Younger age (p = 0.018), male sex (p = 0.011), and higher uveitis grade at presentation (p = 0.031) were associated with greater IMT ( ≥ 2) requirement. 53% had uveitis recurrence compared to 16% with nephritis recurrence. At the most recent visit, nephritis was controlled in 90%, while uveitis in 74%. Four (4%) patients required glaucoma surgery. Nine (8%) patients had renal complications. Most patients with TINU require steroid-sparing IMT for control of uveitis, with nearly half requiring addition of biologic agents. Urinalysis, urine β2M and SCr testing should be considered in children presenting with uveitis, especially when the disease is bilateral and anterior.

Comparison of R-CHOP-14 and R-mini-CHOP in older adults with diffuse large B-cell lymphoma-A retrospective multicenter cohort study.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity, and its incidence increases with age. There is a paucity of data regarding use of biweekly R-CHOP (R-CHOP-14) in patients ≥80 years of age. We performed a retrospective cohort study of patients with DLBCL aged ≥80 years treated with R-CHOP-14 and R-miniCHOP in two academic tertiary centers in Germany between 01/01/2005 and 12/30/2019. Overall, 79 patients were included. Median age was 84 years (range 80-91). Despite higher CR rates with R-CHOP-14 (71.4% vs. 52.4%), no statistically significant difference could be found between patients treated with R-CHOP-14 and R-miniCHOP regarding overall survival (OS) (p = .88, HR 0.94, 95% CI = 0.47-1.90) and progression-free survival (PFS) (p = .26, HR 0.66, 95% CI = 0.32-1.36). At a median follow-up of 40 months, the 2-year OS rates were 56% with R-CHOP-14 and 53% with R-miniCHOP. Two-year PFS rates were 46% for R-CHOP-14 and 50% for R-mini-CHOP. Relative dose intensity of chemotherapy did not correlate with OS (p = .72). With the caveat of a retrospective cohort study, we conclude that lacking a difference in OS, R-miniCHOP should be preferred for most patients with untreated DLBCL aged ≥80 years.

Development and validation of early prediction models for new-onset functional impairment of patients with trauma at hospital discharge.

Early identification of individuals at risk of functional impairment after trauma is crucial for the timely clinical decision-making and intervention to improve reintegration into the society. This study aimed to develop and validate models for predicting new-onset functional impairment after trauma using predictors that are routinely collected within 2 days of hospital admission. In this multicenter retrospective cohort study of acute care hospitals in Japan, we identified adult patients with trauma with independence in carrying out activities of daily living before hospitalization, treated in the intensive or high-dependency care unit, and survived for at least 2 days between April 2008 and September 2023. The primary outcome was functional impairment defined as Barthel Index ≤60 at hospital discharge. In the internal validation data set (between April 2008 and August 2022), using the routinely collected 129 candidate predictors within 2 days of admission, we trained and tuned the four conventional and machine learning models with repeated random subsampling cross-validation. We measured the performance of these models in the temporal validation data set (between September 2022 and September 2023). We also computed the importance of each predictor variable in our model. We identified 8,529 eligible patients. Functional impairment at discharge was observed in 41% of the patients (n = 3,506/8,529). In the temporal validation data set, all four models showed moderate discrimination ability, with areas under the curve above 0.79, and extreme gradient boosting showing the best performance (0.83). In the variable importance analyses, age was the most important predictor, followed by consciousness, severity score, cervical spinal cord injury, mild dementia, and serum albumin level at admission. We successfully developed early prediction models for patients with trauma with new-onset functional impairment at discharge that achieved high predictive performance using routinely collected data within 2 days of hospital admission. Prognostic/Epidemiological; Level II.

Oncologic outcomes based on lymphovascular space invasion in node-negative FIGO 2009 stage I endometrioid endometrial adenocarcinoma: a multicenter retrospective cohort study

BackgroundThe 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system includes lymphovascular invasion quantification as a staging criterion for endometrioid endometrial carcinomas; no lymphovascular invasion and focal invasion (≤4...

A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events.

Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment. We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.

Preoperative and intraoperative tirofiban during endovascular thrombectomy in large vessel occlusion stroke due to large artery atherosclerosis.

The aim of this study is to investigate the efficacy and safety of preoperative versus intraoperative tirofiban in patients with large vessel occlusion (LVO) due to large artery atherosclerosis (LAA). This is a retrospective multicenter cohort study based on the RESCUE-RE (Registration Study for Critical Care of Acute Ischemic Stroke After Recanalization) trial enrolling patients with anterior circulation LVO classified as LAA within 24 h of onset. Patients were divided into three groups: preoperative tirofiban (PT), intraoperative tirofiban (IT), and no tirofiban (NT). Propensity score matching (PSM) was used to balance baseline characteristics. The efficacy outcomes included 90-day functional independence (modified Rankin Scale score = 0-2) and early partial recanalization (EPR; defined as a modified Thrombolysis in Cerebral Infarction score = 1-2a). The safety outcomes included symptomatic intracranial hemorrhage (sICH). A total of 104 matched triplets were obtained through PSM. Compared with NT, PT increased 90-day functional independence (60.8% vs. 42.3%, p = 0.008) and EPR (42.7% vs. 18.3%, p < 0.001) rate, with a tendency to increase the asymptomatic intracranial hemorrhage (aICH) proportion (28.8% vs. 18.3%, p = 0.072). Compared with IT, PT had a higher 90-day functional independence (60.8% vs. 45.2%, p = 0.025) and EPR (42.7% vs. 20.2%, p = 0.001) rate, with no significant difference in sICH (14.4% vs. 7.7%, p = 0.122) and aICH (28.8% vs. 21.2%, p = 0.200). Compared with NT, IT had a lower 90-day mortality rate (9.6% vs. 24.0%, p = 0.005). Tirofiban shows good adjuvant therapy potential in acute ischemic stroke-LVO due to LAA patients. PT is associated with higher rates of EPR and better therapeutic efficacy. In addition, EPR may be a potential way to improve prognosis.

Community-acquired pneumonia in people with Human Immunodeficiency Virus (HIV) during the current era of effective antiretroviral therapy: A multi-center retrospective cohort study.

It is unclear if Human Immunodeficiency Virus (HIV) infection affects the prognosis for community acquired pneumonia (CAP) in the current era of effective anti-retroviral therapy. In this multi-center retrospective cohort study of patients admitted for CAP, we compared the in-hospital mortality rate between people with HIV (PWH) and people without HIV. The study included consecutive patients admitted with a diagnosis of CAP across 31 hospitals in Ontario, Canada from 2015 to 2022. HIV infection was based on discharge diagnoses and anti-retroviral prescription. The primary outcome was in-hospital mortality. Competing risk models were used to describe time to death in hospital or discharge. Potential confounders were balanced using overlap weighting of propensity scores. Of 82,822 patients admitted with CAP, 1,518 (1.8%) patients had a diagnosis of HIV. PWH were more likely to be younger, be male and have less comorbidities. In hospital, 67 (4.4%) PWH and 6,873 (8.5%) people without HIV died. HIV status had an adjusted sub-distribution hazard ratio (sHR) of 1.02 (95% CI 0.80-1.31 P=0.8440) for dying in hospital. Of 1,518 PWH, 440 (29.0%) patients had a diagnosis of acquired immunodeficiency syndrome (AIDS). AIDS diagnosis had an adjusted sHR of 3.04 (95% CI 1.69-5.45 P=0.0002) for dying in hospital compared to HIV without AIDS. People with and without HIV admitted for CAP had a similar in-hospital mortality rate. For PWH, AIDS significantly increased the mortality risk. HIV infection by itself without AIDS should not be considered a poor prognostic factor for CAP.

Effect of sacubitril/valsartan on hospital readmissions in heart failure with reduced ejection fraction in Saudi Arabia: A multicenter retrospective cohort study.

Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that has been shown in multiple clinical trials to have clinical benefits and is recommended by major clinical management guidelines as a first-line treatment for heart failure with reduced ejection fraction (HFrEF). The most significant benefit that was observed in clinical trials is its effect in reducing hospital readmissions. However, little evidence supports its effectiveness in practice, especially in Saudi Arabia. A multicenter retrospective cohort study was conducted using the patient medical records at 2 tertiary hospitals in Saudi Arabia. Eligible patients were adults (≥18 years old) with a confirmed diagnosis of HFrEF who were discharged on either sacubitril/valsartan or angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) in addition to the other recommended therapy for HFrEF. The primary endpoint was the all-cause 30-day readmission rate. The secondary endpoints included all-cause readmissions at 60-day, 90-day, and 12 months. Additionally, 30-day, 60-day, and 90-day readmissions due to HF were evaluated. A total of 398 patients were included in our analysis; 199 (50.0%) received sacubitril/valsartan (group 1), and 199 (50.0%) received ACEI/ARB (group 2). Our results showed that all-cause 30-day readmissions in group 1 were significantly lower than in group 2 (7% vs 25.0%, RR 0.28, 95% Cl 0.16-0.49; P < .001). Additionally, the secondary outcomes showed significantly fewer 60-day, 90-day, and 12-month all-cause readmissions were identified in group 1 compared to group 2 (11% vs 30.7%, RR 0.36, 95% CI 0.23-0.56; P < .001), (11.6%. vs 32.6%, RR 0.35, 95% CI 0.23-0.55; P < .001) and (23.6% vs 51.2%, RR 0.46, 95% CI 0.35-0.62; P < .001), respectively. Furthermore, HF readmissions at 30-day, 60-day, and 90-day in group 1 were significantly lower than in group 2 (P < .05). Sacubitril/valsartan for the treatment of HFrEF is associated with a significantly lower rate of all-cause readmission as well as HF readmissions compared to ACEI/ARB. These benefits extend up to 12 months post-discharge.

Oncologic Outcomes of Patients with Immune Checkpoint Inhibitor Resistant Urothelial Carcinoma Treated with Enfortumab Vedotin and the Impact of Neutrophil-to-Lymphocyte Ratio and Dysgeusia on Overall Survival: A Retrospective Multicenter Cohort Study in Japan.

Randomized phase III trial results have demonstrated enfortumab vedotin (EV), an antibody-drug conjugate (ADC) consisting of an anti-Nectin-4 human IgG1 monoclonal antibody and monomethyl auristatin E, is a useful treatment for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) that progressed after immune checkpoint inhibitor (ICI) therapies. This multicenter retrospective cohort study aimed to identify predictive factors for the efficacy of EV therapy and prolonged overall survival (OS) of patients in clinical practice. This study included patients with la/mUC who received ICI treatment. Patients who subsequently received EV treatment, those who received non-EV chemotherapy, and those who received no treatment were defined as EV, non-EV, and best supportive care (BSC) groups, respectively. The median OS was 20, 15, and 7 months in the EV, non-EV, and BSC groups, respectively (p < 0.001). Patients with la/mUC who had a complete or partial response after EV treatment had a significantly prolonged OS compared with those with stable or progressive disease. Univariate analysis showed age, neutrophil-to-lymphocyte ratio (NLR), dysgeusia, and rash as independent predictors of OS improvement. NLR and dysgeusia were independent predictors of OS after EV in multivariate analysis. Patients without these factors had a significantly prolonged OS compared to those with both factors. In real-world practice, EV therapy is an effective treatment for patients with la/mUC after ICI treatment.

Treatment patterns and outcomes in KRASG12C‐positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study

ObjectivesKRAS mutations, particularly KRASG12C, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRASG12C-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRASG12C-positive advanced NSCLC receiving systemic therapy post-ICI treatment. MethodsFrom the CAnadian CAncers With Rare Molecular Alterations-Basket Real-world Observational Study (CARMA-BROS), a cohort of 102 patients with KRASG12C-positive advanced NSCLC across 9 Canadian centers diagnosed between 2015 and 2021 was analyzed. Clinico-demographic and treatment data were obtained from electronic health records. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models. ResultsThe patients (median age 66 years; 58 % female; 99 % current/former tobacco exposure; 59 % PD-L1 ≥ 50 %), exhibited heterogeneous treatment patterns post-ICI. Most patients received ICIs as a first-line therapy, with varying subsequent lines including chemotherapy and targeted therapy. In patients receiving systemic therapy post-ICI, median overall survival was 12.6 months, and real-world progression-free survival was 4.7 months. KRASG12C-selective targeted therapy post-ICI (n = 20) showed longer real-world progression-free survival compared to single-agent chemotherapy (aHR = 0.39, p = 0.012). ConclusionThis study contributes valuable real-world data on KRASG12C-positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRASG12C-targeted therapies.

A decision tree model for predicting high mono-N-desethylamiodarone concentrations and reducing tissue toxicity in patients with low-dose amiodarone therapy: A multicentral retrospective cohort study.

High plasma levels of mono-N-desethylamiodarone (MDEA), an active amiodarone metabolite, may be associated with tissue toxicity in heart failure (patients with heart rhythm disturbances); therefore, a tool that can identify patients for whom therapeutic drug monitoring (TDM) of MDEA is required. This multicenter study aimed to develop a decision tree (DT) model that can identify patients with heart rhythm disturbances at high MDEA concentrations. A multicenter retrospective cohort study was conducted, including 157 adult patients with heart failure who received oral amiodarone treatment. A χ2 automatic interaction-detection algorithm was used to construct a DT model. In the DT analysis, the dependent variable was set as an MDEA trough plasma concentration of ≥0.6 μg/mL during the steady-state period. Explanatory variables were selected as factors with p < 0.05 in multivariate logistic regression analysis. The adjusted odds ratios for the daily dose of amiodarone and body mass index were 1.01 (95% coefficient interval: 1.008-1.021, p<0.001) and 0.91 (95% confidence interval: 0.834-0.988, p=0.025), respectively. For DT analysis, the risk of reaching plasma MDEA concentrations ≥0.6μg/mL was relatively high, combined with a daily dose of amiodarone >100 mg and body mass index ≤22.3 kg/m2 at 69.0% (20/29), and its trend was also detected in the sensitivity analysis. Patients taking a daily amiodarone dose > 100 mg and with a body mass index ≤22.3 kg/m2 warrant TDM implementation for MDEA to minimize the risk of MDEA-induced tissue toxicity.

Predicting pathological response in esophageal squamous cell carcinoma with longitudinal CT radiomics and disentangled representation learning: a multicenter retrospective cohort study.

Predicting pathological response in esophageal squamous cell carcinoma with longitudinal CT radiomics and disentangled representation learning: a multicenter retrospective cohort study.

Parameters Predictive of Propofol-Associated Acute Pancreatitis in Critically Ill Patients with COVID-19 Pneumonia: A Retrospective Cohort Study.

Propofol, a commonly used agent for short- and long-term sedation, is associated with acute pancreatitis. The main indirect mechanism of propofol-associated acute pancreatitis is by inducing hypertriglyceridemia. Patients with severe coronavirus disease 2019 (COVID-19) pneumonia often require prolonged mechanical ventilation and sedation. We examined the incidence rate of acute pancreatitis among critically ill adults with COVID-19 pneumonia on mechanical ventilation receiving propofol. In addition, we attempted to determine cutoff levels of serum triglycerides and doses of propofol that are predictive of propofol-associated acute pancreatitis. This was a multicenter retrospective cohort study using a large dataset of hospitalized patients with COVID-19. The collected data included the number of days on propofol, cumulative doses of propofol, peak levels of serum triglycerides, serum lipase levels, and abdominal imaging findings. We used receiver-operating characteristic analysis in conjunction with Youden's index to identify the optimal thresholds for propofol administration parameters and levels of triglycerides that would provide maximal sensitivity and specificity for predicting acute pancreatitis. Out of 499 critically ill patients with COVID-19 pneumonia, 154 met the inclusion criteria. Six (4%) patients had suspected acute pancreatitis based on elevated serum lipase levels. Cutoff values greater than 688 mg/dL for peak level of triglycerides, 4.5 days on propofol, 3007 mg/day for average daily propofol dose, and 24 113 mg for cumulative propofol dose were associated with high risk of suspected acute pancreatitis. The negative predictive values for suspected acute pancreatitis using these cutoffs ranged from 98% to 100%. Propofol use in critically ill COVID-19 patients is associated with a low incidence rate of acute pancreatitis. We identified cutoff values for serum triglycerides and cumulative propofol dose that are linked to higher risk of propofol-associated pancreatitis. More research is needed to examine the true incidence of propofol-associated pancreatitis and help develop optimal cutoff values for certain parameters to help guide safe propofol administration.