Total Cohort Research Articles

Survival among 148 patients with an incidentally detected appendiceal tumours at surgery for acute appendicitis: a population-based cohort follow-up study.

To investigate the long-term prognosis of appendiceal tumours incidentally detected at appendicectomy for suspicion of benign appendicitis. A retrospective register-based single centre cohort study was carried out, using data from the local acute appendicectomy quality register of cases operated on at the Department of Surgery, South General Hospital, Stockholm, Sweden. The local colorectal cancer register was also used to identify appendix tumours. The study period was between January 2004 and January 2023. Survival was calculated according to the Kaplan-Meier method. A total of 11,888 patients were registered in the acute acute appendicectomy register, 54% males and 46% females, median age 32 (Q1 = 21, Q3 = 47) (with 33.7% were 41 years or older). From the appendicectomy and colorectal registers 148 (1.2% of the total cohort) appendiceal tumours were found; 60% in females and 40% in males, median age 56 (Q1 = 43, Q3 = 70) (with 78.4% being 41 years or older). Tumours found were: Low grade Appendiceal Mucinous Neoplasms (LAMN, N = 64); Neuroendocrine Tumours (NET N = 24); adenocarcinomas or other form of carcinomas (N = 57); and adenomas (N = 3). The overall 5-year survival in patients operated for LAMN was 96.8%, for NET 93.3% and for adenocarcinoma 69.7%. The overall 5-year survival for all tumour patients was 85.7%. For the younger patients (< 51 years) with LAMN and NET, almost all survived to the end of follow-up. Survival of patients in the carcinoma group was statistically significantly lower than for the LAMN and NET groups, especially in females 51 years or older. In the group of tumour patients undergoing surgery (n = 146), primary surgery was laparoscopic in 47% and open in 52%. Two patients did not undergo surgery due to widespread disease. In 64% of cases operation was acute, whereas it was delayed and/or planned in 34%. Most procedures were laparoscopic appendicectomy 36%, followed by open appendicectomy 30%, right-sided hemicolectomy 14.6% (open 11.6% and laparoscopic 3%, acute operation 5.5%), ileocaecal resection 5% (acute operation 3.4%), and staging laparoscopy 7%. In 38% of the operated patients the tumour was discovered incidentally at histopathology examination. Two patients had CRS and HIPEC as the initial operation. Forthy-three per cent of the 146 tumour patients operated underwent a second procedure: CRS and HIPEC in 23.3% and right-sided hemicolectomy in 13.6% (laparoscopic 8.2% open 5.4%). Survival was high for patients with incidentally detected appendiceal LAMN or NET, but not so for carcinoma. Survival was lower in the carcinoma group older than 50 years, especially those sick and females.

Etiology-Specific Effects of Impaired Functional Status on Liver Transplant Outcomes.

Pre-liver transplant (LT) functional status is an important determinant of prognosis post LT. There is insufficient data on how functional status affects outcomes of transplant recipients based on the specific etiology of liver disease. We stratified LT recipients by etiology of liver disease to evaluate the effects of functional status on post-LT prognosis in each subgroup. 2005-2019 United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) was used to select patients with liver transplant. A total of 14,290 patients were included in the analysis. These patients were stratified by functional status according to Karnofsky Performance Scale (KPS) score: no assistance, some assistance, or total assistance. They were then further divided into six diagnosis categories: metabolic dysfunction-associated steatotic liver disease (MASLD), hereditary disorders, hepatitis C, hepatitis B, autoimmune disease (AID), and alcoholic liver disease (ALD). Primary endpoints included all-cause mortality and graft failure, while secondary endpoints included organ-specific causes of death. Those under the age of 18 and those with non-whole liver or prior liver transplantation were excluded. Patients with MASLD requiring some assistance (aHR: 1.57, 95% CI 1.03-2.39, p = 0.04) and those requiring total assistance (aHR: 2.32, 95% CI 1.48-3.64, p < 0.001) had higher incidences of graft failure compared to those requiring no assistance. Those with MASLD requiring total assistance had a higher all-cause mortality rate than those needing no assistance (aHR: 1.62, 95% CI 1.38-1.89, p < 0.001). Patients with hereditary causes of liver disease showed a lower incidence of all-cause mortality in recipients needing some assistance compared with those needing no assistance (aHR: 0.52, 95% CI 0.34-0.80, p = 0.003). LT recipients with hepatitis C, AID, and ALD all showed higher incidences of all-cause mortality in the total assistance cohort when compared to the no assistance cohort. For the secondary endpoints of specific cause of death, transplant recipients with MASLD needing total assistance had higher rates of death due to general cardiac causes, graft rejection, general infectious causes, sepsis, general renal causes, and general respiratory causes. Patients with MASLD cirrhosis demonstrated the worst overall outcomes, suggesting that this population may be particularly vulnerable. Poor functional status in patients with end-stage liver disease from hepatitis B or hereditary disease was not associated with a significantly increased rate of adverse outcomes, suggesting that the KPS score may not be broadly applicable to all patients awaiting LT.

Surgical Interventions Following Radiotherapy in Spinal Metastases with Intermediate Instability: A Risk Factor Analysis: The Korean Society of Spinal Tumor Multicenter Study (KSST 2022-02).

One important determinant in choosing a treatment modality is spinal instability. Clear management guidelines are suggested for stable and unstable spinal metastatic lesions, but lesions in the intermediate instability category (SINS [spinal instability neoplastic score] score of 7-12) remain a clinical dilemma. This study aims to analyze the risk factors necessitating surgical intervention after radiotherapy (RT) in patients with those lesions. A multicenter cohort of 469 patients with spinal metastases of intermediate instability who received radiotherapy (RT) as the initial treatment between 2019 and 2021 were retrospectively enrolled. All patients were neurologically intact at the time of RT. According to the performance of surgical intervention after RT, various clinical and radiographic risk factors for surgical intervention were compared between surgery and non-surgery groups using uni- and multivariate analyses. A recursive partitioning analysis (RPA) was performed using significant determinants identified in multivariate analysis. The mean age at the time of RT was 59.9 years and there were 198 females. The lung was the most common primary site. During the mean follow-up duration of 18.2 months, surgical treatment was required in 79 (17.9%) of patients. The most common surgical method was decompressive laminectomy with stabilization (62.0%), followed by vertebrectomy with stabilization (22.8%) and stabilization only (15.2%). The mean SINS for the total cohort was 9.0. Multivariate regression analyses revealed that the primary tumor site of the lung, liver, and kidney, higher Bilsky grades of ESCC, lytic bone lesions, and higher EQD210 were significant risk factors for surgical intervention after RT. Among them, Bilsky grade, primary tumor type of the lung, liver, and kidney, and EQD210 were the most important determinants for expecting the probability of surgical intervention on RPA. Surgical intervention was performed in 17.9% of patients with intermediate instability after RT as the initial treatment. The primary tumor site of the lung, liver, and kidney, higher Bilsky grade of ESCC, and EQD210 were the most important determinants for expecting the probability of surgical intervention. Therefore, the optimal treatment strategy needs to be devised by carefully evaluating the risk of surgical intervention.

Association between human leukocyte antigen alleles and COVID-19 disease severity

Backgroundthe human leukocyte antigen (HLA) loci have been widely characterized to be associated with viral infectious diseases. Several studies including various ethnic groups and populations suggested associations between certain HLA alleles and SARS-CoV-2 infection. Despite the numerous associations identified, the role of HLA polymorphisms in determining the individual response to SARS-CoV-2 infection is controversial among different Saudi populations. MethodHere, we performed HLA typing by next-generation sequencing to investigate if variations in polymorphic HLA genes are linked to COVID-19 severity in the Saudi population. Namely, we analyzed HLA loci at allele level in 575 Saudi patients with SARS-CoV-2 infection. HLA class I and class II frequencies in patients were compared with allele frequency data from healthy Saudi population. Resultsin our cohort HLA-A* 02:01:01 G was associated with mild disease but was not associated with moderate and severe disease. HLA-B* 51:01:01 G was protective from severe disease while HLA-B* 50:01:01 G, HLA-C* 06:02:01 G and HLA-DRB1 * 07:01:01 G were associated with risk to severe disease as well as the total COVID-19 cohort. HLA-DRB1 * 15:01:01 G was associated with risk to all severity groups. Conclusionin conclusion, we found significant associations between HLA alleles and COVID-19 disease severity in Saudis. Further studies are warranted to include HLA typing in the workup for any new COVID-19 patients.

Functional status of Indian children with juvenile idiopathic arthritis.

The functional disability status of Indian children with juvenile idiopathic arthritis is unidentified. In this cross-sectional study functional capacity of 60 juvenile idiopathic arthritis patients was assessed by the Childhood Health Assessment Questionnaire. A total of 60 juvenile idiopathic arthritis patients aged ranges from 1 to 12 years were recruited from a teaching hospital in eastern India. A childhood health assessment questionnaire was used to assess the functional health of children. Pain, patient's/parent's global assessment of general well-being, and physician's global assessment were assessed. Childhood health assessment questionnaire disability index for oligoarticular juvenile idiopathic arthritis differed significantly from polyarticular juvenile idiopathic arthritis (P < 0.001), systemic-onset juvenile idiopathic arthritis (P = 0.018) and undifferentiated juvenile idiopathic arthritis (P < 0.001). There was a good to a strong positive correlation between the childhood health assessment questionnaire disability index with pain score, patient's/parent's global assessment score, and physician global assessment score for the total juvenile idiopathic arthritis cohort. regarding juvenile idiopathic arthritis subtypes, significant correlations were noted between the childhood health assessment questionnaire disability index with the patient's/parent's global assessment and physician's global assessment (except for enthesitis-related arthritis). Assessment and documentation of the functional health status of juvenile idiopathic arthritis patients will improve the management of the disease.

Clinical characteristics and prognosis of pancreatitis associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy against various cancers in clinical practice. However, ICIs can cause immune checkpoint inhibitor-associated pancreatic injury, often leading to drug withdrawal, and then patients must go to specialized treatment. The patients, their primary tumors are sensitive to ICIs therapy, may experience treatment delays due to such adverse reactions. Therefore, there is a need for systematic clinical researches on immune-related pancreatic toxicity to provide a clinical basis for its prevention and treatment. This study involved the collection of data from patients treated with ICIs and addressed pancreatic injury with preemptive treatment before continuing ICIs therapy. Then, we also statistically analyzed the incidence of pancreatic injury in patients with different courses and combined treatment, and the success rate of rechallenge treatment. The study included 62 patients, with 33.9% (21/62) experiencing varying degrees of pancreatic injury. Patients with pancreatic injury, 10 cases evolved into pancreatitis, representing 47.6% (10/21) in the pancreatic injury subgroup and 16.1% (10/62) of the total patient cohort. Preemptive treatment was administered to 47.6% (10/21) of patients with pancreatitis, the effective rate was 100%. Among these patients, 70% (7/10) underwent successful rechallenge with ICIs. The occurrence of pancreatic injury was positively correlated with the treatment duration (P < 0.05) but showed no significant correlation with combination therapies (P > 0.05). The likelihood of pancreatic injury increased with longer treatment durations with ICIs; no significant association was found between the incidence of ICIs-related pancreatic damage and combination therapies. Preemptive treatment for immune-related pancreatitis is feasible, allowing some patients to successfully undergo rechallenge with ICIs therapy.

Understanding the Intergenerational Impact of Migration: An Adult Mortality Advantage for the Children of Forced Migrants?

Children of immigrants often have excess mortality rates, in contrast to the low mortality typically exhibited by their parents' generation. However, prior research has studied children of immigrants who were selected for migration, thereby rendering it difficult to isolate the intergenerational impact of migration on adult mortality. We use semiparametric survival analysis to carry out a total population cohort study estimating all-cause and cause-specific mortality among all adult men and women from age of 17 years among all men and women born in 1953-1972 and resident in Finland in 1970-2020. We compare children of forced migrants from ceded Karelia, an area of Finland that was ceded to Russia during the Second World War, with the children of parents born in present-day Finland. Children with two parents who were forced migrants have higher mortality than children with two parents born in Northern, Southern, and Western Finland, but similar or lower mortality than the subpopulation of children whose parents were born in the more comparable areas of Eastern Finland. For women and men, a mortality advantage is largest for external causes and persists after controlling for socioeconomic factors. Our findings suggest that forced migration can have a beneficial impact on the mortality of later generations, at least in the case where forced migrants are able to move to contextually similar locations that offer opportunities for rapid integration and social mobility. The findings also highlight the importance of making appropriate comparisons when evaluating the impact of forced migration.

Clinicopathological characteristics and prognosis of uterine sarcoma: a 10-year retrospective single-center study in China

BackgroundUterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients.MethodsIn this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi’an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis.ResultsThe histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS.ConclusionIn Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.

Client Oriented Scale of Improvement in First-Time and Experienced Hearing Aid Users: An Analysis of Five Predetermined Predictability Categories through Audiometric and Speech Testing.

Objectives: The aim of our investigation was to explore the relationship between unaided pure-tone and speech audiometry and self-reported aided performance measured according to five predetermined COSI categories among first-time hearing aid users and experienced hearing aid users. Methods: Data from 286 patients were retrospectively evaluated. We divided the sample into first-time hearing aid users (G1) and experienced hearing aid users (G2). The correlation between unaided tonal and speech audiometry and five preliminary selected client-oriented scale of improvement (COSI) categories was studied. Results: A greater percentage of hearing aid users aged >80 years and a higher prevalence of severe-to-profound hearing loss in G2 group were observed (p < 0.05). For the total cohort, a mean hearing threshold of 60.37 ± 18.77 db HL emerged in the right ear, and 59.97 ± 18.76 db HL was detected in the left ear (p > 0.05). A significant statistical difference was observed in the group of first-time hearing aid users for the "Television/Radio at normal volume" item, where patients with a lower speech intellection threshold (SIT) were associated with higher COSI scores (p = 0.019). Studying the relationship between the speech reception threshold (SRT) and the COSI item "conversation with 1 or 2 in noise" evidenced worse speech audiometry in patients who scored ≤2 among experienced hearing aid users (p = 0.00012); a higher mean 4-8 kHz frequencies threshold for the better ear was found within the G2 group among those who scored ≤2 in the COSI item "conversation with 1 or 2 in quiet" (p = 0.043). Conclusions: Our study confirms a poor correlation between unaided tonal and speech audiometry and self-reported patient assessment. Although we included only five COSI categories in this study, it is clear that unaided audiometric tests may drive the choice of proper hearing rehabilitation, but their value in predicting the benefit of hearing aids remains limited.

P-584 Occupational paternal risk factors for cryptorchidism and hypospadias in the offspring: a case-control study

Abstract Study question Does paternal occupational exposures to reprotoxic chemical and physical hazards constitute risk factors to cryptorchidism and hypospadias in the offspring? Summary answer Paternal occupational reprotoxic exposures, determined through a job exposure matrix, and paternal rural lifestyle are associated with cryptorchidism, hypospadias, and other genital congenital malformations. What is known already Cryptorchidism and hypospadias are the most common congenital malformations of the male urogenital organs. Over the past century, these congenital malformations, which are associated with testicular cancer and impaired semen quality, have been included into a common disease spectrum known as the testicular dysgenesis syndrome. The association between urogenital congenital malformations and fetal exposure to many factors has been suggested, in particular to genetic and epigenetic factors and environmental factors. There is growing scientific evidence that both maternal and paternal exposure at the time of fertilization play a role after fertilization. Study design, size, duration This is a case-control study with standardized data collection of a 220 father-child cohort recruited from the consultants of our genetic counseling service at the medical university of Sfax (Tunisia), over two years. Participants/materials, setting, methods We compared 110 children diagnosed with congenital malformations to 110 children without any congenital defects. Controls did not differ from the total cohort in confounding variables. Information about paternal jobs held early in pregnancy was collected. Determined via a job exposure matrix, paternal occupational reprotoxic exposures were assessed. Logistic regression analysis was performed to assess the associations between paternal occupational exposures and the congenital testicular dysgenesis syndrome in offspring, including cryptorchidism and hypospadias. Main results and the role of chance 75.54% of children had congenital heart defects and 24.54% of them had genital malformations (n = 27). Paternal occupational exposures to pesticides were associated with the risk of developing birth defects (odds ratio = 17.568 (95% CI), 2.258-136.673). Our results indicate that paternal exposure to pesticides, phthalates, alkylphenolic compounds and other endocrine disruptors was associated with genital and cardiac birth defects. Both cryptorchidism and hypospadias in offspring were associated with paternal rural lifestyle as well as the absence of a maternal job. Limitations, reasons for caution The cohort size in this case-control study may limit the statistical power of the logistical regression to detect associations. Additionally, cases and controls may be selected in a way that does not represent the general population accurately. This can introduce bias and affect the external validity of the study. Wider implications of the findings Including paternal exposures in subsequent investigations of risk factors for cryptorchidism and hypospadias, and further exploring the connection between paternal pesticide exposure and epigenetic alterations, may offer insights into their impact on paternal spermatogenesis, sperm small RNAs, and the potential development of congenital testicular dysgenesis syndrome in future generations. Trial registration number 0400/2022

Pyroptosis-related long-noncoding RNA signature predicting survival and immunotherapy efficacy in patients with lung squamous cell carcinoma

Pyroptosis-related long-noncoding RNAs (PRlncRNAs) play an important role in cancer progression. However, their role in lung squamous cell carcinoma (LUSC) is unclear. A risk model was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis based on RNA sequencing data from The Cancer Genome Atlas database. The LUSC cohort was divided into high- and low-risk groups based on the median risk score. For the prognostic value of the model, the Kaplan–Meier analysis, log-rank test, and Cox regression analysis were performed. A nomogram was constructed to predict the prognosis of patients, using a risk score and clinical parameters such as age, sex, clinical stage, and tumor node metastasis classification (TNM) stage. Afterwards, six common algorithms were employed to assess the invasion of immune cells. The Gene Set Enrichment Analysis (GSEA) was conducted to identify differences between patients at high and low risk. Furthermore, the pRRophetic package was employed to forecast the half-maximal inhibitory doses of prevalent chemotherapeutic drugs, while the tumor immune dysfunction and exclusion score was computed to anticipate the response to immunotherapy. The expression levels of the seven PRlncRNAs were examined in both LUSC and normal lung epithelial cell lines using RT-qPCR. Proliferation, migration, and invasion assays were also carried out to investigate the role of MIR193BHG in LUSC cells. Patients in the low-risk group showed prolonged survival in the total cohort or subgroup analysis. The Cox regression analysis showed that the risk model could act as an independent prognostic factor for patients with LUSC. The results of GSEA analysis revealed that the high-risk group showed enrichment of cytokine pathways, Janus tyrosine kinase/signal transducer and activator of the transcription signalling pathway, and Toll-like receptor pathway. Conversely, the low-risk group showed enrichment of several gene repair pathways. Furthermore, the risk score was positively correlated with immune cell infiltration. Moreover, patients in the high-risk category showed reduced responsiveness to conventional chemotherapeutic medications and immunotherapy. The majority of the long noncoding RNAs in the risk model were confirmed to be overexpressed in LUSC cell lines compared to normal lung epithelial cell lines by in vitro tests. Further studies have shown that downregulating the expression of MIR193BHG may inhibit the growth, movement, and infiltration capabilities of LUSC cells, whereas increasing the expression of MIR193BHG could enhance these malignant tendencies. This study found that PRlncRNAs were linked to the prognosis of LUSC patients. The risk model, evaluated across various clinical parameters and treatment modalities, shows potential as a future reference for clinical applications.

798 Improving the Use of Ultrasound Imaging in the Diagnosis and Assessment of Paediatric Patients Admitted with Suspected Appendicitis

Abstract Aim To investigate the barriers to and rate of ultrasonography use to facilitate the diagnosis of suspected appendicitis and assess its effect on negative appendicectomy rates in concordance with GIRFT guidelines for children with abdominal pain. Method Retrospective single-site data on paediatric patients presenting with suspected appendicitis was collected over 6 months, using operative and admission records, imaging requests and histology results. An anonymous survey was distributed amongst Surgical clinicians to determine the perceived impact of access to and influencers of ultrasonography use for children. Results Of 91 patients, 35 underwent a diagnostic laparoscopy. The operation findings were: 23% (8) not acute appendicitis, 23% (8) perforated or complex appendicitis and 54% (19) “other” acute appendicitis. 85% (30) of patients who were surgically managed did not have an ultrasound before theatre. 23% (21) of the total cohort underwent an ultrasound and none of the scans suggested acute appendicitis. Of these, 76% (16) of patients were managed non-operatively. Of the 5 patients who underwent an ultrasound and proceeded to laparoscopy; none had intraoperative findings of appendicitis. Further analysis aims to investigate why ultrasound was utilised for only 23% of patients and to clarify the decision-making processes behind a “straight to theatre” versus an “imaging-first” approach. Conclusions The negative paediatric appendicectomy rate in this District General Hospital was 23%. According to this data, ultrasonography is a reliable rule-out tool for suspected appendicitis and more frequent use could reduce unnecessary operations.

Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy: A Single-Center Experience

BackgroundThe use of surgery in patients with locally advanced pancreatic cancer (LAPC) following induction chemotherapy is increasing. However, most series do not report on the total cohort of patients undergoing surgical exploration; therefore, this single-center study investigates outcomes among all consecutive patients with LAPC who underwent surgical exploration.MethodsWe conducted a retrospective, single-center analysis including all consecutive patients with LAPC (Dutch Pancreatic Cancer Group criteria) who underwent surgical exploration with curative intent (January 2014–June 2023) after induction therapy. Primary outcomes were resection rate and overall survival (OS) from the time of diagnosis.ResultsOverall, 127 patients underwent surgical exploration for LAPC, whereby 100 patients (78.7%) underwent resection and 27 patients (21.3%) underwent a non-therapeutic laparotomy due to the extent of vascular involvement (n = 11, 8.7%) or occult metastases (n = 16, 12.6%). The overall in-hospital/30-day mortality rate was 0.8% and major morbidity was 31.3% (in patients after resection: 1.0% and 33.3%, respectively). The overall 90-day mortality rate was 5.5%, which included 3.1% mortality due to disease progression. Resection was associated with longer median OS {29 months (95% confidence interval [CI] 26–43) vs. 17 months (95% CI 11–26); p < 0.001} compared with patients undergoing non-therapeutic laparotomy, with corresponding 5-year OS rates of 28.4% and 7.7%. In Cox proportional hazard regression analysis, only pancreatic body/tail tumors independently predicted OS (hazard ratio 1.788 [95% CI 1.042–3.068]).ConclusionThis single-center series found a resection rate of 78.7% in patients with LAPC selected for surgical exploration, with a low risk of mortality and morbidity in all explored patients and a 5-year OS rate after resection of 28.4%.

Clinical effectiveness of coronavirus disease 2019 vaccination in patients with multiple sclerosis stratified by disease-modifying treatment.

Coronavirus disease 2019 (COVID-19) vaccination has been associated with a dampened humoral and/or cellular immune response in patients with multiple sclerosis (MS) who were concurrently on disease-modifying treatment (DMT) with B-cell depleting agents or sphingosine-1-phosphate receptor modulators (S1PRMs). Our main goal was to investigate the impact of these DMT classes on the clinical effectiveness of COVID-19 vaccination. Since March 2020, demographics and clinical data of patients with MS who developed COVID-19 have been collected at the Belgian National MS Centre in Melsbroek. Patients were considered to be 'protected by vaccination' if they were (i) fully vaccinated and (ii) tested positive for COVID-19 in the period ranging from 14 days to 6 months after the last administered vaccine. On 19 December 2022, 418 COVID-19 cases were retrospectively identified in 389 individual patients. Hospitalization and mortality rates resulting from the infection were 10.8% and 2.4%, respectively. Being 'unprotected by vaccination' was significantly associated with a worse COVID-19 outcome (i.e., hospitalization and/or death) in the total cohort (N = 418, odds ratio [OR] 3.96), in patients on ongoing DMT other than anti-CD20 agents or S1PRMs (N = 123, OR 31.75) and in patients without DMT (N = 182, OR 5.60), but not in those receiving anti-CD20 agents (N = 91, OR 0.39); the S1PRMs subgroup was considered too small (22 infections) for any meaningful analysis. Coronavirus disease 2019 vaccination protects against severe infection in patients with MS but it was not possible to confirm this effect in those on DMT with B-cell depleting agents.

Age-Based Outcomes After Surgical Aortic Valve Replacement With Bioprosthetic Versus Mechanical Valves

Recommendations for prosthesis type in older patients who underwent surgical aortic valve replacement (SAVR) are established, albeit undervalidated. The purpose of this study is to compare outcomes after bioprosthetic versus mechanical SAVR across various age groups. This was a retrospective study using an institutional SAVR database. All patients who underwent isolated SAVR were compared across valve types and age strata (<65 years, 65 to 75 years, >75 years). Patients who underwent concomitant operations, aortic root interventions, or previous aortic valve replacement were excluded. Objective survival and aortic valve reinterventions were compared. Kaplan-Meier survival estimation and multivariate regression were performed. A total of 1,847 patients underwent SAVR from 2010 to 2023. A total of 1,452 patients (78.6%) received bioprosthetic valves, whereas 395 (21.4%) received mechanical valves. Of those who received bioprosthetic valves, 349 (24.0%) were aged <65 years, 627 (43.2%) were 65 to 75 years, and 476 (32.8%%) were older than 75 years. For patients who received mechanical valves, 308 (78.0%) were aged <65 years, 84 (21.3%) were between 65 and 75 years, and 3 (0.7%) were >75 years. The median follow-up in the total cohort was 6.2 (2.6 to 8.9) years. No statistically significant differences were observed in early-term Kaplan-Meier survival estimates between SAVR valve types in all age groups. However, the cumulative incidence estimates of aortic valve reintervention were significantly higher in patients aged under 65 years who received bioprosthetic than those who received mechanical valves, with 5-year reintervention rates of 5.8% and 3.1%, respectively (p = 0.002). On competing risk analysis for valve reintervention, bioprosthetic valves were significantly associated with an increased hazard of aortic valve reintervention (hazard ratio 3.35, 95% confidence interval 1.73 to 6.49, p <0.001). In conclusion, SAVR with bioprosthetic valves (particularly, in patients aged <65 years) was comparable in survival to mechanical valve SAVR but significantly associated with increased valve reintervention rates.

Correction of omega-3 fatty acid deficiency and improvement in disease activity in patients with systemic lupus erythematosus treated with krill oil concentrate: a multicentre, randomised, double-blind, placebo-controlled trial

ObjectiveOmega-3 polyunsaturated fatty acids (PUFAs) play a critical role in regulating inflammation and lipid metabolism. This study sought to ascertain the frequency of omega-3 deficiency in patients with SLE and...

Infective endocarditis and spondylodiscitis-impact of sequence of surgical therapy on survival and recurrence rate.

To date, there are no standardized treatment algorithms or recommendations for patients with infective endocarditis (IE) and concomitant spondylodiscitis (SD). Therefore, our aim was to analyse whether the sequence of surgical treatment of IE and SD has an impact on postoperative outcome and to identify risk factors for survival and postoperative recurrence. Patients with IE underwent surgery in 4 German university hospitals between 1994 and 2022. Univariable and multivariable analyses were performed to identify possible predictors of 30-day/1-year mortality and recurrence of IE and/or SD. From the total IE cohort (n = 3991), 150 patients (4.4%) had concomitant SD. Primary surgery for IE was performed in 76.6%, and primary surgery for SD in 23.3%. The median age was 70.0 (64.0-75.6) years and patients were mostly male (79.5%). The most common pathogens detected were enterococci and Staphylococcus aureus followed by streptococci, and coagulase-negative Staphylococci. If SD was operated on first, 30-day mortality was significantly higher than if IE was operated on 1st (25.7% vs 11.4%; P = 0.037) and we observed a tendency for a higher 1-year mortality. If IE was treated 1st, we observed a higher recurrence rate within 1 year (12.2% vs 0%; P = 0.023). Multivariable analysis showed that primary surgery for SD was an independent predictor of 30-day mortality. Primary surgical treatment for SD was an independent risk factor for 30-day mortality. When IE was treated surgically 1st, the recurrence rate of IE and/or SD was higher.

Long-term durability of bioprosthetic aortic valve replacement in young patients with bicuspid aortic stenosis

ObjectiveTo examine long-term surgical aortic valve replacement (SAVR) outcomes for young (ie, younger than age 65 years) patients with bicuspid aortic valve and aortic stenosis (AS) with or without concomitant aneurysm. BackgroundThere are few studies evaluating the early and late outcomes of SAVR in young patients (younger than age 65 years) with bicuspid aortic valve and AS. MethodsUsing institutional data from 2004 through 2022, 498 patients with bicuspid aortic valve younger than age 65 years underwent SAVR for AS with bioprosthetic valves. We examined operative outcomes, long-term valve durability, and reintervention. ResultsThe total cohort comprised 281 patients undergoing isolated SAVR and 217 with concomitant aneurysm repair (SAVR/aneurysm). The average age was 55 ± 8 years, with Society of Thoracic Surgeons predicted risk of mortality score of median 0.7 (IQR 0.5, 1.0) and mean valve size of 25 mm. Operative mortality (0.7% vs 1.4%; P = .77) was similar between SAVR and SAVR/aneurysm patients. Predischarge permanent pacemaker implantation occurred in 1.6% (8 out of 498) patients. During overall follow-up of 5.0 years (IQR 1.8-9.9; range, 0.2-18.2 years), the cumulative incidence of reintervention at 10 years for structural valve degeneration (n = 33), including valve-in-valve (n = 15) was 6.6% (8.1% SAVR vs 4.5% SAVR/aneurysm; P = .66). No mortality was observed for valve-in-valve or redo-SAVR. Moderate or greater aortic regurgitation and paravalvular leak were observed in 6.5% and 0.3%, respectively, at most recent follow-up. ConclusionsBicuspid AS is common in patients younger than 65 years and management includes consideration of future valve intervention. SAVR confers excellent operative and reoperative outcomes, 10-year durability, and valve function. These results may support initial SAVR when considering lifetime management of AS.

Left ventricular morphology and geometry in élite athletes characterised by extreme anthropometry

ObjectiveThe aim of the study was to explore the individual impact of BMI and height on LV size and geometry in a cohort of healthy athletes. MethodsFrom a total cohort of 1857 healthy élite athletes (21 ± 5 years, males 70%) investigated with ECG and echocardiogram, we considered three groups: Group 1 n = 50: BMI ≥ 30 and height < 1.90 m; Group 2 n = 87: height ≥ 1.95 m and BMI < 30; control Group 3 n = 243: height < 1.90 m and BMI = 20–29. ResultsBSA was ≤2.3 m2 in 52% of athletes in group 1 and 47% of athletes in group 2. Athletes in group 1 and in group 2 showed an enlarged LV end-diastolic diameter (LVEDD) (57 ± 6 vs 57 ± 4 vs 53 ± 4 mm in Group 3); 50% of athletes in group 1 and 38% of athletes in group 2 exhibited a LVEDD > 57 mm (p = 0.23). LV wall thickness was higher in group 1 (11 ± 1 vs 10 ± 2 mm in Group 2, p = 0.001). Concentric hypertrophy or concentric remodelling was found in 20% of athletes in group 1 vs 7% of athletes in group 2 (p = 0.04). Athletes of group 1 with BSA ≤ 2.3 m2 showed lower LVEDD (53 ± 5 vs 60 ± 5 mm, p < 0.001), similar LV wall thickness (10 ± 1 vs 11 ± 1 mm, p = 0.128) and higher prevalence of concentric hypertrophy or concentric remodelling (31% vs 8%, p = 0.04) compared to those with BSA > 2.3 m2. ConclusionAthletes with high BMI have similar LV dimensions but greater wall thickness and higher prevalence of concentric remodelling compared to very tall athletes. Athletes with high BMI and large BSA have the widest LV dimensions.

Development and Validation of the Hospital Medicine Safety Sepsis Initiative Mortality Model

When comparing outcomes after sepsis, it is essential to account for patient case mix to make fair comparisons. We developed a model to assess risk-adjusted 30-day mortality in the Michigan Hospital Medicine Safety sepsis initiative (HMS-Sepsis). Can HMS-Sepsis registry data adequately predict risk of 30-day mortality? Do performance assessments using adjusted vsunadjusted data differ? Retrospective cohort of community-onset sepsis hospitalizations in the HMS-Sepsis registry (April 2022-September 2023), with split-derivation (70%) and validation (30%) cohorts. We fit a risk-adjustment model (HMS-Sepsis mortality model) incorporating acute physiologic, demographic, and baseline health data and assessed model performance using concordance (C) statistics, Brier's scores, and comparisons of predicted vsobserved mortality by deciles of risk. We compared hospital performance (first quintile, middle quintiles, fifth quintile) using observed vsadjusted mortality to understand the extent to which risk adjustment impacted hospital performance assessment. Among 17,514 hospitalizations from 66 hospitals during the study period, 12,260 hospitalizations (70%) were used for model derivation and 5,254 hospitalizations (30%) were used for model validation. Thirty-day mortality for the total cohort was 19.4%. The final model included 13 physiologic variables, two physiologic interactions, and 16 demographic and chronic health variables. The most significant variables were age, metastatic solid tumor, temperature, altered mental status, and platelet count. The model C statistic was 0.82 for the derivation cohort, 0.81 for the validation cohort, and≥ 0.78 for all subgroups assessed. Overall calibration error was 0.0%, and mean calibration error across deciles of risk was 1.5%. Standardized mortality ratios yielded different assessments than observed mortality for 33.9%of hospitals. The HMS-Sepsis mortality model showed strong discrimination and adequate calibration and reclassified one-third of hospitals to a different performance category from unadjusted mortality. Based on its strong performance, the HMS-Sepsis mortality model can aid in fair hospital benchmarking, assessment of temporal changes, and observational causal inference analysis.