Multicenter Retrospective Cohort Study Research Articles

Short- and long-term outcomes of conversion surgery for initially unresectable advanced gastric cancer: A Japanese multicenter retrospective cohort study.

402 Background: The efficacy of conversion surgery in patients with unresectable advanced gastric cancer at the initial diagnosis who converted to be resectable due to remarkable response to chemotherapy is unclear. To evaluate short- and long-term outcomes of conversion surgery for initially unresectable cStage IVB/pStage IV gastric cancer as the basic data for the JCOG2301 trial, which is a randomized controlled trial comparing conversion surgery with continuation of chemotherapy, a multicenter retrospective cohort study was conducted in the Stomach Cancer Study Group of the Japan Clinical Oncology Group. Methods: Inclusion criteria were as follows; (1)gastric cancer with at least one of following distant metastasis at the initial diagnosis; (i) peritoneal metastasis (PER) diagnosed by imaging examination or P1b or P1c disease diagnosed by laparoscopy or laparotomy, (ii) multiple liver metastasis (HEP) more than three lesions, and (iii) distant lymph node metastasis (LYM) beyond paraaortic lymph node station 16a2/b1, (2) conversion to be resectable after systemic chemotherapy, (3) surgery aiming at an R0 resection of the primary and remaining lesions between April 2010 and September 2017. Clinical data were retrospectively obtained from electronic patient records of 58 institutions. Results: Atotal of 241 patients were included to the study. Initial unresectable factors were PER, HEP, and LYM in 132(55%), 37(15%), and 63(26%) patients, respectively, and 9(4%) patients had two or more factors. Conversion to be resectable obtained during the first and second/later line chemotherapy was in 209 (87%) patients and 32 (13%), respectively. 182(76%), 29(12%), and 30(12%) patients underwent R0, R1, and R2 resection, respectively. The incidence of postoperative complication of Clavien-Dindo Grade II or higher was 24% and no surgery-related death was observed. The median overall survival (mOS) from surgery was 45.4 (95%CI 30.9-61.4) months in R0 resection, 16.6 (11.5-18.5) months in R1, and 20.9 (11.3-35.6) months in R2. In case of R0 resection, the mOS from surgery was 34.4 (95%CI 26.5-59.2) months in PER, 55.9 (21.8-96.7) months in HEP, 54.6 (30.9-98.3) months in LYM, and not reached (19.7-NA) in two or more factors. Conclusions: Conversion surgery appears to be safe and a promising treatment strategy for patients who have initially unresectable advanced gastric cancer and presented remarkable response to systemic chemotherapy.

Psychological health status after major trauma across different levels of trauma care: A multicentre secondary analysis.

Concentration of trauma care in trauma network has resulted in different trauma populations across designated levels of trauma care. Describing psychological health status, by means of the impact event scale (IES) and the hospital anxiety and depression scale (HADS), of major trauma patients one and two years post-trauma across different levels of trauma care in trauma networks. A multicentre retrospective cohort study was conducted. aged ≥ 18 and an Injury Severity Score (ISS) > 15, surviving their injuries one year after trauma. Psychological health status was self-reported with HADS and IES. Subgroup analysis, univariate, and multivariable analysis were done on level of trauma care and trauma region for HADS and IES as outcome measures. Psychological health issues were frequently reported (likely depressed n = 31, 14.7 %); likely anxious n = 32, 15.2 %; indication of a post-traumatic stress disorder n = 46, 18.0 %). Respondents admitted to a level I trauma centre reported more symptoms of anxiety (3, P25-P75 1-6 vs. 5, P25-P75 2-9, p = 0.002), depression (2, P25-P75 1-5 vs. 5, P25-P75 2-9, p < 0.001), and post-traumatic stress (6, P25-P75 0-15 vs. 13, P25-P75 3-33, p = 0.001), than patients admitted to a non-level I trauma centre. Differences across trauma regions were reported for depression (3, P25-P75 1-6 vs. 4, P25-P75 2-10, p = 0.030) and post-traumatic stress (7, P25-P75 0-18 vs. 15, P25-P75 4-34, p < 0.001). Major trauma patients admitted to a level I trauma centre have more depressive, anxious, and post-traumatic stress symptoms than when admitted to a non-level I trauma centre. These symptoms differed across trauma regions, indicating populations differences. Level of trauma care and trauma region are important when analysing psychological health status.

Development and validation of a deep learning–based pathomics signature for prognosis and chemotherapy benefits in colorectal cancer: A retrospective multicenter cohort study.

298 Background: The current TNM staging system fails to provide adequate information for prognosis and adjuvant chemotherapy benefits in colorectal cancer (CRC). Pathomics, an emerging field, shows promise in improving prognosis estimation and decision-making. In this study, we developed and validated a pathomics signature (PS CRC ) that directly analyzes hematoxylin and eosin–stained slides using deep learning to predict outcomes. Methods: A total of 883 whole slide images from two cohorts, Harbin Medical University Cancer Hospital and The Cancer Genome Atlas (TCGA), were retrospectively analyzed. An interpretable, multi-instance deep learning model was proposed to establish the PS CRC . Shapley additive explanations were employed to interpret the model's decisions, and gradient-weighted class activation mapping was applied to visualise the pathological phenotypes of the PS CRC . The transcriptomics data from TCGA cohort was used to explore the potential pathogenesis underlying the PS CRC . Results: The PS CRC was identified as an independent prognostic factor associated with both overall survival and disease-free survival. Incorporating the PS CRC into the TNM stage model resulted in a significant improvement in prognosis estimation, as evidenced by a notable increase in net reclassification improvement and integrated discrimination improvement. Moreover, among stage II and III CRC patients with low levels of PS CRC , satisfactory benefits from chemotherapy were observed. Notably, the main underlying features of PS CRC include tumor cell infiltration, adipocyte accumulation, fibrous tissue deposition, and stromal infiltration. Transcriptome analysis further support the relevance of PS CRC to tumor progression and immune suppression. Conclusions: Our finds highlight the significant potential of histopathology images-based deep learning in predicting prognosis and assess therapeutic response of CRC. The PS CRC could serve as an effective tool in clinical decision for CRC management, providing insights into the underlying pathogenic mechanisms. However, prospective studies are still necessary for further validation.

Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.

Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management. This is a multi-centre international retrospective cohort study with data collected up to May 2023 from 17 centres across 6 countries. Outcomes included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for anti-PD-(L)1 and subsequent therapy. One-hundred and eighty-five advanced MCC patients received anti-PD-(L)1 therapy. At median follow-up of 28.7 months (95 % CI: 21.4-38.3), ORR was 57.3 %, median DOR was 42.8 months (95 % CI, 25.8 - not reached (NR)), median PFS was 14 months (95 % CI, 8.1- 19.8), and median OS was 42.8 months (95 % CI, 30.3 - NR). One-hundred and eight patients (59 %) experienced progressive disease; 50 % (n = 54/108) with primary resistance and 26 % (n = 28/108) with secondary resistance. Fifty patients (27 %; n = 50/185) received subsequent systemic therapies (+/- local therapy) with response data; 18 (36 %; n = 18/50) received doublet platinum chemotherapy (ORR 67 %, DOR 5.0 months [95 % CI; 3.7 - NR]) and 16 (32 %; n = 16/50) were rechallenged with anti-PD-(L)1 (ORR 56 %, DOR 20.2 months [95 % CI; 8.3 - NR]). The most common subsequent treatment for patients with primary resistance was chemotherapy, while those with secondary resistance most frequently underwent further anti-PD-(L)1 therapy in combination with other therapies. Despite both therapies demonstrating promising ORR, doublet platinum chemotherapy had a poorer DOR compared to anti-PD-(L)1 rechallenge.

Major Pathologic Response as a Prognostic Surrogate in Esophageal Squamous Cell Carcinoma Patients Receiving Neoadjuvant Chemotherapy/Chemoimmunotherapy: a Multi-center Cohort Study

To determine the prognostic and survival surrogate value of major pathologic response (MPR) in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemotherapy/chemoimmunotherapy(nCT/nICT) and surgery. A retrospective multi-center study cohort study enrolled 305 ESCC patients who underwent neoadjuvant chemotherapy/chemoimmunotherapy followed by esophagectomy. Endpoints included recurrence-free survival (RFS), locoregional recurrence-free survival(L-RFS), distant metastasis-free survival(D-MFS), and recurrence patterns. The Cox regression analysis and Harrell's C-index were used to analyze survival differences and surrogate endpoints. The Kaplan-Meier method was used for the subgroup analysis in two subgroups(the patients receiving nICT and patients receiving nCT) and the prognostic value analysis of adjuvant therapy in non-MPR and MPR patients. Of the 305 patients, 105 achieved MPR, demonstrating a significantly improved RFS (P value<0.001), L-RFS (P value<0.001), and D-MFS (P value=0.003). MPR was identified as an independent risk factor for RFS(HR:0.415, 95%CI:[0.227, 0.759], P value=0.004) and demonstrated equal predictive capacity to be a surrogate of survival endpoints with T stage and N stage(Harrell's C-index: 0.613). In subgroup analysis, patients with MPR showed better survival outcomes in subgroups that received neoadjuvant chemoimmunotherapy (P value=0.012) and neoadjuvant chemotherapy(P value<0.001). Additionally, adjuvant therapy did not confer additional survival benefits to both MPR and non-MPR patients. Compared with patients who achieved MPR, non-MPR patients exhibited a higher recurrence rate, although the recurrence sites were similar between the two groups. MPR can serve as an independent prognostic factor and a surrogate of survival endpoints in ESCC patients undergoing nCT/nICT. Besides, as a potential indicator for postoperative management, MPR can provide reference basis and evidence support in clinical practice.

Results of a multicenter retrospective cohort study evaluating the safety and efficacy of FTD/TPI plus ramucirumab in advanced gastric cancer (HGCSG2302).

351 Background: In advanced gastric cancer, trifluridine/tipiracil (FTD/TPI) is one of the standard treatments for later-line chemotherapy. Ramucirumab (RAM), an anti-VEGFR-2 monoclonal antibody, has shown promising efficacy in combination with FTD/TPI in phase II studies conducted in Japan, suggesting that this combination could improve treatment outcomes. However, there remains a paucity of real-world clinical data comparing the efficacy and safety of FTD/TPI monotherapy and FTD/TPI plus RAM combination therapy in general clinical practice. Methods: This retrospective analysis to evaluate safety and efficacy included patients with gastric cancer who were received FTD/TPI plus RAM combination therapy or FTD/TPI monotherapy between August 2019 and March 2023 at 21 institutions. Results: 164 patients were analyzed, 38 patients in the RAM combination group and 126 in the FTD/TPI monotherapy group. The distribution of treatment lines (third/fourth/fifth) was 10/13/15 in the RAM group and 26/54/46 in the monotherapy group, respectively. RAM had been previously administered to 34 patients (89.5%) in the RAM group. Objective response rate and disease control rate were 11.1% / 55.6% (OR 2.0, 95% C.I. 0.84-4.77, p=0.126) in the RAM group and 5.5% /38.5% (OR 2.0, 95% C.I. 0.84-4.77, p=0.126) in the monotherapy group, respectively. Median progression-free survival (PFS) was 3.5 months in the RAM group and 2.1 months in the monotherapy group (HR 0.69, 95% C.I. 0.49-1.02, p=0.06), respectively. Median overall survival (OS) was 8.4 months in the RAM group and 5.8 months in the monotherapy group (HR 0.82, 95% C.I. 0.54-1.25, p=0.350), respectively. Grade 3 neutropenia was reported in 48.6%/52.4% (p=0.707), and there were no significant differences in other adverse event profiles between the two groups. Additionally, in the RAM group, a comparison between patients receiving standard dosing (2 weeks on/2 weeks off; n=7) and those on biweekly dosing (1 week on/1 week off; n=24) showed no notable differences in efficacy or safety. Conclusions: FTD/TPI plus RAM combination therapy showed a trend toward prolonged PFS compared to FTD/TPI monotherapy, but no significant difference in OS.

Association Between Preterm Birth and Fulfillment of Desired Permanent Contraception.

In cases of preterm delivery, the Medicaid sterilization policy mandates a signed consent form at least 72h before surgery for permanent contraception, which is less than the 30day minimum waiting period for term births. This study evaluated the association between preterm birth and fulfillment of planned permanent contraception. This was a secondary analysis of a multi-center retrospective cohort study of 3013 patients with a postpartum contraceptive plan of permanent contraception. Primary outcomes were permanent contraception fulfillment, compared between preterm and term deliveries. Secondary analyses examined moderation by delivery mode and insurance type. At hospital discharge, patients who had a preterm delivery were less likely to undergo desired permanent contraception than those with a term delivery (adjusted odds ratio (aOR): 0.67, 95% CI: 0.53-0.84), and this finding persisted up to one year postpartum (aOR: 0.65, 95% CI: 0.53-0.8). For patients with cesarean deliveries, the odds of permanent contraception fulfillment were significantly lower among those with preterm compared to term deliveries (aOR: 0.54, 95% CI: 0.39-0.76). Among patients with Medicaid insurance, those who delivered preterm were less likely than those who delivered term to undergo desired permanent contraception (aOR: 0.66, 95% CI: 0.59-0.88). Patients delivering preterm face barriers to fulfillment of desired permanent contraception postpartum. Prioritization of contraceptive goals is important for patient autonomy and increasing equitable access to contraception for all.

Predictors of cytomegalovirus infection in patients with connective tissue disease treated by pulsed methylprednisolone therapy: a multicenter retrospective cohort study

BackgroundCytomegalovirus (CMV) can cause life-threatening diseases in immunosuppressed patients. Some of the patients with connective tissue disease develop CMV infection, and approximately half of this group has been reported to have received pulsed-methylprednisolone (p-MPSL) therapy. This study aimed to identify predictors of the onset of CMV infection in patients receiving p-MPSL therapy for connective tissue disease.MethodsThis was a retrospective, multicenter cohort study. We included patients who received p-MPSL therapy for connective tissue disease and had CMV antigenemia measured between April 2011 and December 2020. Peripheral blood cell data before the start of p-MPSL therapy and at the start of steroid tapering were collected in addition to baseline characteristics, including age, sex, and body mass index. CMV infection was defined as detection of one or more CMV antigen-positive cells (CMV-positive). The study examined and compared the CMV-positive group with the CMV-negative group. Logistic regression analysis was used to explore the factors associated with CMV antigen positivity. Receiver operating characteristic curve analysis was used to identify the cut-off values for the factors associated with CMV antigen sensitivity.ResultsOf the 200 patients included, 87 had antigen positivity. Logistic regression analysis showed that age ≥ 65 years [adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.54–4.92] and platelet count less than 30.20 × 104 /µL [aOR: 4.38, 95%CI: 2.21–8.68] at baseline were significantly associated with CMV antigen positivity. Lymphocyte count < 1440 /µL [aOR: 5.36, 95% CI: 1.96–14.65], neutrophil-to-lymphocyte ratio (NLR) ≥ 3.42 [aOR: 7.31, 95% CI: 2.52–21.22], and platelet-to-lymphocyte ratio (PLR) ≥ 145.28 [aOR:6.10, 95% CI: 2.24–16.64] at the start of steroid tapering also increased the OR for CMV infection. The areas under the receiver operating characteristic curves for lymphocytes, NLR, and PLR were 0.742, 0.693, and 0.673 respectively.ConclusionPlatelet count, lymphocyte count, NLR, and PLR may be crucial predictors of the onset of CMV infection in patients with connective tissue disease. These easily obtainable factors may be clinically useful as predictors of CMV infection. A potential research area would be to validate the parameters in a prospective patient population.

Prognostic factors in severe dengue patients: A multi-center retrospective cohort study.

Early detection of severe dengue (SD) and appropriate management are crucial in reducing the case fatality rate. The objective of this study was to investigate the clinical characteristics of SD and identify independent risk factors associated with mortality among SD patients. A retrospective study was conducted at two medical center hospitals between 2002 and 2019, involving patients aged ≧18 years with laboratory-confirmed SD. This study included 294 patients with SD, of whom 203 (69%) survived and 91 (31%) died. Among the 294 SD patients, 103 (35%) experienced acute kidney injury, 54 (18.4%) had pneumonia, and 19 (6.5%) had bacteremia. Among the 286 patients with available alanine aminotransferase (ALT) data, 41 (14.3%) experienced severe hepatitis (ALT>1000U/L). The median time from illness onset to death among the 91 SD patients who died was 5 days. Multivariable regression analysis revealed increasing odds of death associated with older age (odds ratio [OR], 1.037; 95% confidence interval [CI], 1.009-1.066), altered consciousness (OR, 8.591; 95% CI, 2.914-25.330), gastrointestinal bleeding (OR, 1.939; 95% CI, 1.037-3.626), and leukocytosis (OR, 2.504; 95% CI, 1.124-5.578) upon arrival, as well as organ impairment during hospitalization, including acute kidney injury (OR, 2.627; 95% CI, 1.373-5.028), severe hepatitis (OR, 5.324; 95% CI, 2.199-12.889), and pneumonia (OR, 2.250; 95% CI, 1.054-4.802). Our findings underscore the importance of early recognition and intervention by frontline physicians in identifying SD patients at high risk of mortality. This information can significantly contribute to reducing fatalities and improving the overall management of SD cases.

Comparative Outcomes of Babesiosis in Immunocompromised and Non-Immunocompromised Hosts: A Multicenter Cohort Study.

Babesiosis poses significant risks of adverse outcomes in individuals with immunocompromising conditions (IC) and asplenia/hyposplenia (AH). This study compares clinical outcomes between these vulnerable groups and immunocompetent patients. A multicenter retrospective cohort study included adult patients with laboratory-confirmed babesiosis from 2009 to 2023. Complications, management, and outcomes were compared between patients with IC/AH (ICAH) and without ICAH (immune intact cohort). Of 225 patients (mean age 66 years, 36% female), 112 were ICAH. ICAH patients had higher median peak parasitemia (2.8% vs. 0.9%, p<0.0001) and higher rates of complications, including acute kidney injury (24% vs. 11%, p=0.016), acute respiratory distress syndrome (11% vs. 4%, p=0.041), and were more likely to undergo packed red blood cell transfusion (31% vs. 17%, p=0.023) and exchange transfusion (18% vs. 6%, p=0.008). Treatment duration was longer in the ICAH cohort (median 27 vs. 10 days, p<0.001), particularly in those with both IC and AH (median 43 days, p=0.003). ICAH patients had higher 12-month all-cause mortality (7% vs. 1%, p=0.019) and recurrence rates (8% vs. 0%, p=0.001). Hematologic malignancy (OR=7.0, p=0.023) and B-cell-depleting therapies (OR=9.4, p=0.015) were significant predictors of recurrence. Despite most patients undergoing follow-up testing with blood smears and PCR, these did not reliably predict recurrence. Patients with ICAH with babesiosis experience more severe disease and higher complication rates. Follow-up testing, including blood smear and PCR, did not reliably predict recurrence, highlighting the need for more effective monitoring strategies in these high-risk populations.

Predisposing Factors of Progression from Refractory Status Epilepticus to Super-Refractory Status Epilepticus in ICU-Admitted Patients: Multicenter Retrospective Cohort Study in a Resource-Limited Setting.

Super-refractory status epilepticus (SRSE) is an extremely serious neurological emergency. Risk factors and mechanisms involved in transition from refractory status epilepticus (RSE) to SRSE are insufficiently studied. This was a multicenter retrospective cohort study of consecutive patients diagnosed and treated for RSE at two reference hospital over 5years in Ecuador. A total of 140 patients were included. Potential demographic, clinical, and treatment variables that may predict progression from refractory to SRSE were analyzed. Super-refractory status epilepticus was identified in 67/140 (48%) of patients. In univariate analyses, level of consciousness on hospital admission (Glasgow Coma Score < 12, odds ratio [OR] 2.9, p < 0.01), traumatic brain injury (OR 2.3, p = 0.05), acute etiology (OR 3.0, p = 0.04), higher Status Epilepticus Severity Score (STESS) (OR 1.7, p < 0.01), and new clinical or electrographic seizure within 6h (OR 4.2, p < 0.01) of starting anesthetic infusion were important factors related to super-refractory disease. The best independents predictors of SRSE when the presence of other potential factors were considered for multivariate analysis. Two models were calculated to avoid interactions between similar variables. Glasgow Coma Score on hospital admission < 12 (OR 3.1 [95% confidence interval {CI} 1.16-8.29], p = 0.02) and new clinical or electroencephalography (EEG) seizure after first 6h of starting anesthetic infusion (OR 3.1 [95% CI 1.36-7.09], p = 0.01) were associated with higher risk of progression to SRSE in model 1. In contrast, model 2 indicated that patients with STESS ≥ 3 points (OR 2.9 [95% CI 1.24-6.65], p = 0.01) and new clinical or EEG seizure after 6h starting anesthetic infusion (OR 3.0 [95% CI 1.32-6.97], p = 0.01) were the factors independentlyrelated to super-refractory disease. The rate of patients with RSE admitted to intensive care units developing SRSE was high. Low level of consciousness on admission, higher STESS scores, and patients who did not achieve total control of clinical or EEG seizure in the first 6h of starting intravenous anesthetic infusion may be early indicators of SRSE.

Validation of a New Classification for Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants: Insights from a Large Japanese Cohort.

A recent scoping review identified histological chorioamnionitis (HCA), small for gestational age (SGA), and bubbly/cystic appearance on chest X-ray (bubbly/cystic CXR) as risk factors for severe bronchopulmonary dysplasia (BPD). To further validate these results, a large-scale database was analyzed. This retrospective multicenter cohort study included infants born at <28 weeks' gestational age between 2003 and 2016. The validated risk factors identified from the scoping review were analyzed for independent associations with severe BPD using multivariable logistic regression. Additionally, the association of these factors with long-term outcomes at 3 years, including home oxygen therapy (HOT) and neurodevelopmental impairments (NDIs), were analyzed. Among 15,834 extremely preterm infants, HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were significantly and independently associated with severe BPD (adjusted odds ratio, 1.20; 95% confidence interval, 1.06-1.36) (1.73; 1.51-1.98) (1.79; 1.60-2.01), respectively. These three factors were also linked to HOT at 3 years (1.54; 1.14-2.08) (1.70; 1.21-2.39) (2.63; 1.94-3.56), respectively. Their combination significantly increased the prevalence of severe BPD and HOT at 3 years, particularly with bubbly/cystic CXR. Only SGA was independently associated with NDIs in BPD infants (1.55; 1.32-1.83). HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were identified as important risk factors for severe BPD and long-term respiratory outcomes. While further research is needed to validate their role in endotype-specific classification of BPD, these findings may contribute to early prognostic strategies and targeted interventions before 36 weeks' postmenstrual age.

Metastatic Status and Dissection Effect of Regional/Extraregional Lymph Nodes in Japanese Patients with Squamous Cell Carcinoma of the Anal Canal: A Multicenter Retrospective Cohort Study

Metastatic Status and Dissection Effect of Regional/Extraregional Lymph Nodes in Japanese Patients with Squamous Cell Carcinoma of the Anal Canal: A Multicenter Retrospective Cohort Study

Predictors of functional recovery following surgical repair of quadriceps tendon rupture: insights from a German multicentre study.

More extensive and cohesive studies on quadriceps tendon rupture (QTR) repair surgery are required to guide effective treatment strategies. Therefore, in this study, we aimed to identify predictors of subjective functional recovery following QTR repair surgery. This multicentre retrospective cohort study enrolled 191 adults (age ≥ 18years) who underwent surgical unilateral QTR repair (2010-2022) and had ≥ 1-year postoperative follow-up at three trauma centres in Germany. Multiple linear regression and moderation analyses evaluated seven patient-centred factors and eight treatment-related predictors of the International Knee Documentation Committee (IKDC) and Tegner-Lysholm Knee scores. The participants ( meanage = 62.3years) had mean (standard deviation) IKDC and Tegner-Lysholm Knee scores of 67.4 (19.4) and 74.8 (22.5), respectively. Male sex, lower body mass index (BMI), shorter time to surgery, and early rehabilitation adoption predicted higher functional scores (p < 0.05). Smoking and suturing techniques showed no significantmain effects. Age was negatively correlated with IKDC scores when transosseous sutures were applied but not when suture anchors were used. Notably, 6% of the cohort were affected by complications such as re-rupture or deep vein thrombosis. Patient-centred factors (sex and BMI) and treatment-related factors (timing of surgery and rehabilitation protocols) significantly influence postoperative functional outcomes in patients with QTR. Early surgical intervention and dynamic rehabilitation protocols are important for optimising recovery, and suture anchor techniques may be advantageous in older patients. Further research is essential to improve QTR management strategies and enhance patient outcomes. IV-Retrospective cohort study without a comparison group.

Comparative Analysis of the Effectiveness of Generic and Brand-Name Cefepime: A Multicenter Retrospective Cohort Study

The clinical effectiveness of generic and brand-name cefepime in real-world settings remains unclear. Given the potential implications for healthcare costs and patient outcomes, this study aims to compare the efficacy and safety of these two formulations. We conducted a multicenter, retrospective cohort study (2017–2022), enrolling adults who received either generic or brand-name cefepime as initial monotherapy for at least three consecutive days. Demographics, comorbidities, disease severity, infection sites, cefepime dosage, and serial laboratory data were analyzed. Propensity score matching was employed to adjust key confounding variables. A total of 2370 patients were included, 877 receiving generic and 1493 receiving brand-name cefepime. After matching, no significant differences were observed in primary (in-hospital mortality, p = 0.841) or secondary outcomes (30-day mortality, readmission, length of stay, ICU stay, and incidence of seizures; all p &gt; 0.05). Biomarker trends and clinical recovery patterns were comparable across groups. Receiving the maximal dosage or not did not alter outcomes among both groups. Generic cefepime showed comparable efficacy and safety to brand-name cefepime, offering a cost-effective alternative without compromising therapeutic outcomes.

Efficacy analysis of drug-eluting beads transcatheter arterial chemoembolization combining systemic chemotherapy and immune checkpoint inhibitors in unresectable intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study based on propensity score matching

ObjectiveTo investigate the efficacy and safety of drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE) combined with systemic chemotherapy and immune checkpoint inhibitors in the treatment of unresectable intrahepatic cholangiocarcinoma.MethodsThis study used retrospective cohort analysis to collect the clinical data of 209 patients with unresectable intrahepatic cholangiocarcinoma treated in Linyi Cancer Hospital, Affiliated Zhongshan Hospital of Dalian University, Affiliated Central Hospital of Dalian University of Technology from January 2020 to January 2024. The patients were divided into observation group and control group based on their treatment plans. The observation group was treated with DEB-TACE combined with systemic chemotherapy and immune checkpoint inhibitor, and the control group was treated with simple systemic chemotherapy and immune checkpoint inhibitor. Based on propensity score matching analysis, the clinical treatment efficacy, survival prognosis, and incidence of adverse reactions of two groups of patients were evaluated.Results82 patients in the observation group received DEB-TACE combined with systemic chemotherapy and immune checkpoint inhibitors, The control group of 127 patients were treated with systemic chemotherapy and immune checkpoint inhibitors. After a propensity score matching analysis to control for the consistency of patient age, sex, tumor size, tumor number, Child grade, ECOG score, and tumor stage. Propensity score matching analysis created 71 pairs of patients in 2 groups. The objective response rate (ORR, 76.06%) and disease control rate (DCR, 97.18%) in the observed group were significantly higher than that in the control group (52.11%, 85.92%), Progression-free survival (PFS, 10 months) and overall survival (OS, 17 months) were higher than the control group (8 months, 11 months). The Cox proportional hazards model analysis revealed that, Child grade and treatment modality were independent predictors of PFS and OS in patients. The adverse effects during treatment were similar in the two groups, with no statistical difference.ConclusionsCompared with systemic therapy alone (systemic chemotherapy + immune checkpoint inhibitor), combined DEB-TACE improves the tumor control rate of patients with unresectable intrahepatic cholangiocarcinoma, extends the survival time and without increasing treatment-related adverse effects, which is a safe and feasible treatment modality.

Multicenter Analysis of Acute Retinal Necrosis: Clinical Characteristics, Viral Pathogens, and Diagnostic Predictive Factors

ABSTRACT Purpose This multicenter study aimed to investigate the clinical characteristics and factors associated with specific viral pathogens in patients with acute retinal necrosis (ARN). Methods A retrospective multicenter cohort study included ARN patients who underwent aqueous or vitreous polymerase chain reaction (PCR) testing. Multivariable mixed-effects Poisson regression was used to identify factors associated with viral pathogens. Results A total of 56 patients (65 eyes) with ARN were included, with a mean age was 39.9 ± 23.2 years. Anterior chamber cell showed significant inflammation in 89.2%, while vitreous haze was present in 100%. Multifocal retinitis was found in 92.3% of cases. Among these, 49.2% had diffuse or confluent patterns, 15.4% were circumferential, and 23.1% showed satellite lesions. Additionally, 18.5% were ameboid or scalloped shape, while 9.2% had wedge shapes. Varicella zoster virus (VZV) was the most common pathogen (30.8%), followed by Herpes simplex virus (HSV) (13.8%), Cytomegalovirus (CMV) (10.8%), Epstein-Barr virus (EBV) (9.2%), and human herpesvirus (HHV) (3.0%). Co-infections were observed in 20% of eyes. CMV-related ARN was significantly associated with wedge-shaped retinitis (aRR 4.19) and immunocompromised host (aRR 8.8). Younger age and optic disc edema (aRR 5.41) were correlated with HSV-related ARN. Conclusion VZV was the predominant viral pathogen, with the increasing prevalence of CMV, EBV, and co-infection. Wedge-shaped retinitis and immunocompromised status were notably associated with CMV-related ARN, findings that may guide antiviral therapy decisions in settings where PCR diagnostics are either unavailable or delayed, ultimately improving visual outcomes.

Reassessing the Role of Morning Cortisol in Adrenal Insufficiency Diagnosis: Insights from a Multicentric Cohort.

The diagnosis of adrenal insufficiency (AI) is challenging due to nonspecific symptoms. Measuring 8 AM serum cortisol levels is a common screening test, but its accuracy in predicting AI remains uncertain. This study aimed to evaluate the predictive diagnostic value of basal morning cortisol levels in suspected AI cases and compare them with levels in healthy individuals. We have conducted a retrospective multicentric cohort study. The study included an epidemiological cohort (patients with AI suspicion) and a control cohort (healthy volunteers). In the epidemiological cohort an ACTH-stimulation test was performed to confirm (AI group) or exclude (non-AI group) the disease. We have included 273 individuals (168 suspected AI cases and 105 controls). Basal cortisol levels were higher in the control group compared to the AI-suspected group (9.9±3.2 μg/dl vs. 7.7±3.3 μg/dl, p<0.001), though both were below the 15 μg/dl recommended threshold for excluding AI. Within the epidemiological cohort, even after a propensity score matching, taking into consideration sex, age and AI symptoms complaints, no significant difference in basal cortisol levels was found between patients with and without AI [6.10 (4.43; 8.45) vs. 7.14 (4.68; 12.15), p=0.128]. Logistic regression and ROC curve analyses showed a low predictive value for basal cortisol, with a positive predictive value of 18.9% and low specificity. AI patients more frequently experienced hypotension and nausea, compared with non-AI patients. Morning cortisol levels alone are unreliable for diagnosing AI. Revising cortisol cutoffs and incorporating symptom-based criteria may improve diagnostic accuracy.

P0602 Long-term effectiveness and safety of ustekinumab dose escalation in patients with refractory ulcerative colitis: a multicenter retrospective cohort study

Abstract Background Ustekinumab dose escalation (DE) may be an effective strategy to recapture clinical response in patients with ulcerative colitis (UC). The aim of this study was to assess the real-world long-term effectiveness and safety of ustekinumab DE in patients with refractory UC. Methods This multicenter retrospective cohort study included patients with refractory UC who received at least one IV induction ustekinumab dose between January 2016 and November 2021. We compared ustekinumab DE to no DE, examining clinical, biochemical, and endoscopic disease outcomes. The primary endpoint was corticosteroid-free clinical remission (partial Mayo score ≤ 2 without systemic corticosteroids) at the end of follow-up. Cox-proportional hazards regression analysis was performed for factors associated with time to DE, and a Kaplan-Meier plot was created for visualizing drug persistence probabilities. Results We enrolled 121 patients. Eighty-one patients (67%) underwent DE during a median follow-up of 141 weeks. Corticosteroid-free clinical remission at the end of follow-up was achieved for 53.2% (DE group) and 59.0% (non-DE group). In the DE group, 53% discontinued ustekinumab, mainly due to a lack of effectiveness. At the end of follow-up, 47% of DE patients remained on ustekinumab, compared to 55% in the non-DE group. Ustekinumab persistence probability after 2 years was 40% (DE group) versus 79% (non-DE group). Only 2 patients discontinued ustekinumab for adverse events. Conclusion Our results indicate that DE is a common method for optimizing ustekinumab treatment in refractory UC. While DE appears safe, effectiveness and drug persistence of DE beyond 2 years are limited.

P0905 Incidence, risk factors, and management of acne in IBD patients on JAK Inhibitors: A multicentre retrospective cohort study (The JAKNE Project)

Abstract Background Tofacitinib, filgotinib, and upadacitinib, are Janus kinase inhibitors (iJAKs) approved for inflammatory bowel disease (IBD) treatment. Although no comparative studies exist, potential differences in efficacy and safety are attributed to in vitro-demonstrated affinity of each molecule for different JAK isoforms. JAK1 plays a crucial role in modulating cytokine-mediated immune responses, such as IL-6 and interferon, which are involved in inflammation and skin homeostasis. Its inhibition can promote conditions that may trigger acne. Acne may be increased in iJAK-treated patients, meaning a clinical challenge for gastroenterologists. This study aims to identify the proportion of patients treated with iJAKs who develop acne, describe acne characteristics, risk factors, and management strategies. Methods A retrospective study was conducted at two referral centers in Madrid, Spain, including all IBD patients who had received iJAK therapy. Demographic data, disease-related variables, and acne characteristics (if appropriate) were collected. Results A total of 152 patients included; 64 (42%) were women. Eighty-two patients (54%) had ulcerative colitis, 70 (46%) had Crohn’s disease. Median age was 42.5 years (IQR 33.5-55). Sixty patients (39%) were treated with tofacitinib, 82 (54%) with upadacitinib, and 10 (7%) with filgotinib. Twenty-four patients (16%) developed acne during iJAK treatment: 75% were mild, with only 1 severe case (4%). Acne occurred early (median onset 1.8 months, IQR 0-3), predominantly on the face (92%) and/or trunk (46%). Acne morphology included comedones (75%), papules (50%), pustules (37%), nodular-cystic (12%), scarring (12%); 42% showed more than one morphology. Eleven patients received specific acne treatment: 54% topical (antiseptics, benzoyl peroxide, retinoids), 41% systemic (antibiotics, retinoids, antiandrogens), and 29% combined treatment. Only 3 patients (12% of those with acne; 2% overall) had to discontinue iJAK treatment, with acne resolving in all cases. Variables associated with acne development included high iJAK doses (p=0.001), age &amp;lt;35 years (p=0.005), and a history of acne (p=0.02). Acne developed in 21%, 8% and 2% of upadacitinib, tofacitinib and filgotinib treated patients respectively, though these differences were not statistically significant (p=0.09). Conclusion Acne occurred in a significant proportion of iJAK treated patients, was typically mild and manageable with specific dermatological intervention. Only a minority of cases required treatment discontinuation. Risk factors for iJAK-associated acne included dosage, younger age, and acne history. A trend toward a higher incidence of acne associated with upadacitinib may reflect its greater affinity for JAK1.