Multicenter Cohort Research Articles

P-086 Consequences of elevated levels of DNA fragmentation and its influence on pregnancy – A multicentric cohort analysis

Abstract Study question Does an abnormal DNA Fragmentation Index impact the clinical outcomes of patients undergoing IVF treatment? Summary answer Statistical differences were seen in biochemical, implantation, clinical, and ongoing pregnancy rate in sperms with high and low DFI scores with autologous and donated oocytes. What is known already Sperm chromatin integrity is associated with embryo development and clinical outcomes of an IVF cycle. DNA Fragmentation Index (DFI) is a diagnostic tool for the detection of spermatozoa with damaged chromosomes in the ejaculate. DNA fragmentation is a significant cause of day 3 embryo arrest and the development of poor-quality embryos. The interventions associated with elevated levels of DFI are ICSI, lifestyle changes and antioxidant therapies. However, the published data regarding the potential of embryo development with high DFI is limited to the sample size thus, encouraging a need for more research in this area. Study design, size, duration The study is population-based and included 768 male patients who underwent DFI score detection across 44 centers at Indira IVF Hospital Private Limited from January 2023 to September 2023. The abstinence period for all the patients was recorded during the DFI detection. After the DFI assessment patients were classified into normal DFI score ( < =15%) (n = 203) and abnormal DFI score (>15%) (n = 565). Participants/materials, setting, methods The retrospective cohort analysis was performed on our databank on the male patients regardless of their age (21-50), ethnicity, and medical history. DFI was calculated using a Sperm Chromatin Dispersion assay. Patients were categorized into two groups: Normal DFI ( < =15%) and Abnormal DFI (>15%). The characteristics of population along with clinical outcomes were evaluated after transferring embryos fertilized with normal DFI sperm and abnormal DFI sperm. The data was analyzed and estimated by SPSS software. Main results and the role of chance Our analyses discovered that embryos fertilized with sperms of normal DFI score have significantly enhanced the likelihood of implantation compared with embryos fertilized with sperms of abnormal DFI (50.27% v/s 44.40%; p = 0.047). Simultaneously, early pregnancy was evaluated by determining the values of beta-HCG in blood, also known as biochemical pregnancy rate (BPR). The embryos fertilized with sperms of normal DFI score significantly enhanced the BPR compared with embryos fertilised with sperms of abnormal DFI (67% v/s 59.1%; p = 0.048). Clinical Pregnancy Rate (CPR) defined as presence of a heartbeat of gestational sac observed during the 6-week scan. Furthermore, it was evaluated that the CPR showed a significant enhancement in embryos fertilized with sperms of normal DFI score in comparison with embryos fertilized with sperms of abnormal DFI (65.5% v/s 57.9%; p = 0.034). However, it was noticed that male DFI score had no impact on the miscarriage rate of embryos inseminated with normal DFI score and abnormal DFI score (7.52% v/s 7.34%; p = 0.687). Moreover, the pregnancy was tracked, and it was revealed that embryos inseminated with sperms of normal DFI score significantly enhanced the ongoing pregnancy till 12 weeks compared with embryos inseminated with sperms of abnormal DFI score (60.6% v/s 53.6%; p = 0.039). Limitations, reasons for caution Embryos are known to have a self-correct mechanism to correct the presence of mosaicism in the embryos. Hence, the oocyte quality also affects the outcomes of the IVF cycle. Therefore, using a high grade of the oocyte for the patients with abnormal DFI score can be useful. Wider implications of the findings Our data suggest that abnormal DFI have an impact on the clinical outcomes of an IVF cycle. Therefore, examining the levels of DNA Fragmentation is utmost imperative for a successful pregnancy. Trial registration number not applicable

P-087 Obstetrical and perinatal outcomes from intracytoplasmic sperm injection couples with oocyte donation are not affected by advanced paternal age measured as a continuous variable

Abstract Study question Does paternal age (PA), considered a continuous variable, have any effect on obstetrical and perinatal outcomes in intracytoplasmic sperm injection (ICSI) with donated oocytes? Summary answer PA does not affect clinically relevant obstetrical and perinatal outcomes, but it significantly increases the pregnancy’s duration in ICSI with autologous sperm and donated oocytes. What is known already Currently there has been an evident delay in childbearing, therefore studies relating advanced PA with reproductive risks are increasing and results are controversial. These studies frequently study PA by dividing it in groups arbitrarily constructed, but probably a more precise evaluation is obtained using PA as a continuous variable. Furthermore, oocyte donation standardizes female factor, to some extent, allowing a more realistic male factor evaluation. In this regard, we aimed to evaluate the effect of PA at conception (continuous variable) on obstetrical and perinatal outcomes in ICSI couples with autologous sperm and donated oocytes in a large population of patients. Study design, size, duration This retrospective observational multicentric cohort study evaluated data from couples that performed an ICSI between January 2008 and March 2020 using autologous sperm and donated oocytes. We included only singleton deliveries and the first delivery of each couple. PA was analysed as a continuous variable, considered more informative in comparison to its analysis as categorical. Data available and included consisted of 15,696 patients who had a delivery with or without a live birth. Participants/materials, setting, methods PA ranged from 21-54 years. Clinical database was constructed with reproductive outcomes from electronic medical records. Erroneous or incomplete data were removed. Statistical analysis included a descriptive analysis, followed by univariate and multivariate models using binary logistic regression or linear regression. We adjusted for maternal age and body mass index, PA, fresh sperm concentration and progressive motility, cycle type, gestational age, transfer on day 5 and delivery type (when appropriate). P < 0.05 was considered statistically significant. Main results and the role of chance Mean PA was 41.45 (41.38-41.51). We included a total of 15,696 deliveries and 15,673 live births. Results from multivariate models are presented as adjusted odd ratio or regression coefficient with 95% confidence intervals and adjusted p. In terms of obstetrical outcomes, PA results were 1.086 (0.959-1.229) p = 0.194 for gestational diabetes, 0.963 (0.849-1.093) p = 0.561 for anemia, 0.947 (0.837-1.072) p = 0.388 for hypertension, 0.959 (0.878-1.048) p = 0.356 for preterm birth and 0.986 (0.929-1.046) p = 0.641 for caesarean delivery. Regarding perinatal outcomes, PA results were 0.442 (0.005-0.879) p = 0.047 for gestational age, -0.216 (-15.559-15.126) p = 0.978 for infant weight, 1.101 (0.941-1.288) p = 0.231 for low birth weight (<2,500 g), 0.710 (0.463-1.088) p = 0.116 for very low birth weight (<1,500g), 0.988 (0.933-1.047) p = 0.684 for female sex, 0.002 (-0.076-0.08) p = 0.96 for length, -0.012 (-0.088-0.064) p = 0.763 for cranial perimeter, 0.991 (0.876-1.12) p = 0.88 for NICU admission, and 0.027 (-0.028-0.083) p = 0.337, 0.025 (-0.012-0.061) p = 0.18 and -0.045 (-0.096-0.007) p = 0.089 for Apgar 1, 5 and 10 minutes, respectively. According to our results, PA does not affect clinically relevant outcomes for the health during pregnancy and of the infant. However, PA significantly increases the duration of the pregnancy in ICSI with autologous sperm and donated oocytes. Limitations, reasons for caution The study’s major strengths are the consideration of PA as a continuous variable, the use of oocyte donation (controlling female factors) and the inclusion of a huge sample size. However, due to its retrospective nature there are some biases derived from the clinical practice and the presence of missing data. Wider implications of the findings Current evident delay in childbearing merits further research on the effect of PA on reproductive outcomes, addressed in this study. Our study suggests that PA is not associated with obstetrical and perinatal outcomes, except for gestational age, which sends a hopeful message to fathers of advanced paternal age. Trial registration number not applicable

Anaesthetic mortality in cats: A worldwide analysis and risk assessment.

Patient safety is essential in small animal anaesthesia. This study aimed to assess anaesthesia-related deaths in cats worldwide, identify risk and protective factors and provide insights for clinical practice. A prospective multicentre cohort study of 14,962 cats from 198 veterinary centres across different countries was conducted. Data on anaesthesia-related deaths, from premedication up to 48 hours postextubation, were collected. Logistic regression was used to analyse patient demographics, American Society of Anesthesiologists (ASA) classification, procedure type and anaesthetic drugs. The anaesthesia-related mortality was 0.63%, with 74.5% of deaths occurring postoperatively. Cats with cachexia, a higher ASA status or who underwent abdominal, orthopaedic/neurosurgical or thoracic procedures exhibited elevated mortality. Mechanical ventilation use was associated with increased mortality. Mortality odds were reduced by the use of alpha2-agonist sedatives, pure opioids in premedication and locoregional techniques. Limitations include non-randomised sampling, potential biases, unquantified response rates, subjective death cause classification and limited variable analysis. Anaesthetic mortality in cats is significant, predominantly postoperative. Risk factors include cachexia, higher ASA status, specific procedures and mechanical ventilation. Protective factors include alpha2-agonist sedatives, pure opioids and locoregional techniques. These findings can help improve anaesthesia safety and outcomes. However, further research is required to improve protocols, enhance data quality and minimise risks.

1190 Clinical Features and Outcomes from the Acute PresentatiOn of coLorectaL Cancer – an internatiOnal Snapshot (APOLLO) – an International Prospective Audit

Abstract Aim The APOLLO study aimed to describe the international variation in the presentation, management and outcomes of patients presenting acutely with colorectal cancer. Method APOLLO was an international prospective, multicentre cohort study delivered through the EuroSurg student and trainee-led collaborative network. Adult patients presenting acutely with colorectal cancers were included. The primary outcome was 90-day mortality. Country-level variation was analysed using funnel plots. Results 1414 patients (216 centres, 39 countries) were enrolled (median age 70 years; 645 females [45.6%]; ASA Grade I-II: 689 [48.7%]). Common presentations were bowel obstruction (n=774, 54.7%), gastrointestinal haemorrhage (n=297, 21.0%),bowel perforation (n=161, 11.4%). Overall, 56.9% of patients presented with a new diagnosis of cancer (n=804), 13.9% presented while awaiting elective surgery (n=196), and 9.3% while undergoing neoadjuvant therapy (n=132). Most cases were managed with curative intent (n=805, 56.9%). Of the 1022 patients undergoing surgery, 813 underwent surgical resection (79.5%), 582 underwent stoma formation (56.9%), and 498 (48.7%) underwent primary anastomosis. Only 57 patients underwent colonic metallic stenting (4.0%). Overall, 90-day mortality was 19.4%; 90-day surgical mortality was 13.9% and 90-day non-operative mortality was 33.7%. There was significant variation in overall mortality, but not surgical mortality, between countries after case-mix adjustment. Conclusions Emergency colorectal cancer presentations carry significant mortality with and without surgery. Many acute presentations are in patients with known colorectal cancer awaiting treatment. Operative mortality is similar globally, but overall mortality varies between countries. Further work is needed to guide individualised decision making on who benefits from acute surgery with curative-intent.

Serum androgen dynamics in young women aged 18-40 treated with chemotherapy for breast cancer: an observational, multicentric, prospective study in France

Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients <40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. Trial registration: ClinicalTrial.gov identifier NCT01114464

P-652 Chronic kidney disease and female reproductive hormonal profile: A multi-centre cohort study

Abstract Study question Does Chronic Kidney Disease (CKD) impact female reproductive hormone profiles? Summary answer Women with CKD had significantly lower AMH and testosterone, and significantly higher LH levels. There were no differences in FSH, oestradiol, prolactin and progesterone. What is known already Chronic diseases, such as CKD, is rising in women of reproductive age. It is expected that the prevalence of CKD in adults will increase to 16.7% in 2030.Coupled with improvements in obstetric care and advancement in assisted reproductive technology, more women with CKD are seeking to conceive with ART. It is known that CKD reduces fertility, but underlying mechanisms are not fully understood. It is proposed that CKD leads to dysregulation of the hypothalamus-pituitary-ovarian (HPO) axis, but studies are small, use outdated assays, are done at different times in the menstrual cycle and do not compare with healthy controls. Study design, size, duration Observational cohort study involving women with CKD and healthy women of reproductive age without underlying medical conditions was conducted between August 2021-September 2022.Women with CKD were identified from four units to attend a study visit at a tertiary fertility unit.Healthy controls were recruited via word of mouth and from couples within the unit undergoing treatment for male factor infertility.For the study to be powered 100 women with CKD and 50 healthy controls were recruited. Participants/materials, setting, methods Ethical approval was provided by the Health Research Authority (IRAS 285546) and written informed consent was obtained from participants.Serum Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), prolactin, testosterone, oestradiol, progesterone, Anti Mullerian Hormone (AMH) and b-HCG were taken between the first and fifth day of menstrual cycle. If there was amennorhoea, bloods were taken on a day suiting them. Comparisons between controls and CKD Stage utilised t-test and Mann Whitney U tests according to data-distribution. Main results and the role of chance 101 women with CKD and 63 healthy women were recruited. The mean age of women in the CKD group was 35.1± 6.7 years and of controls was 33.44 ±4.8 years, median BMI for CKD women was 25.45 kg/m2 (IQR 22.7,29.4) and controls was 24.5 kg/m2 (IQR 22,26.7).The renal cohort had similar numbers in each of the four CKD stages. 20.8% women had renal transplants.The two cohorts were matched for age and BMI. Median AMH (13.6(IQR 3,4,28.7) vs 18.4 (IQR 11.2,33.6) pmol/L;p=0.03) was significantly lower in the renal group than controls. Median testosterone concentrations (0.6 (IQR 0.5,0.9) vs 0.5 (IQR 0.4,0.7)nmol/L; p = 0.01) were significantly lower in women with CKD even from stage 1 CKD. LH (4.4 (IQR 3.2,5.5) vs 5.9 (IQR 3.8,9.4) IU/L;p=0.001) concentrations were significantly higher in women with CKD compared to controls but there were no differences in FSH, oestradiol, prolactin and progesterone. LH increased and testosterone and AMH concentrations fell with CKD severity. Interestingly, b-HCG was &amp;gt;6 IU/L in 3.0% (3/101) patients with CKD. When stratified by CKD stage; CKD stage 2 and onwards had significantly higher LH concentrations (p = 0.03).CKD stage 3 and above participants had significant lower AMH concentrations (p = 0.002).This is at a later stage of CKD than previously published. Limitations, reasons for caution Although this is the largest study of its kind known to explore female hormonal profiles in women with CKD, the numbers are still limited. In addition, our population had a mixed ethnic background but due to the small numbers we were unable to analyse the results per ethnic category. Wider implications of the findings This is the largest prospective study comparing fertility hormonal profiles in women with CKD and healthy controls. Unfortunately, there remains a paucity of evidence on the effects of CKD on female fertility. Future work includes exploring longitudinal changes which will better facilitate patients to make informed and timely fertility-related decisions. Trial registration number 285546

A comparative cohort study of surgical approaches for adult spinal deformity at a minimum 2-year follow-up.

This study was a retrospective multi-center comparative cohort study. A retrospective institutional database of operative adult spinal deformity patients was utilized. All fusions > 5 vertebral levels and including the sacrum/pelvis were eligible for inclusion. Revisions, 3 column osteotomies, and patients with < 2-year clinical follow-up were excluded. Patients were separated into 3 groups based on surgical approach: 1) posterior spinal fusion without interbody (PSF), 2) PSF with interbody (PSF-IB), and 3) anteroposterior (AP) fusion (anterior lumbar interbody fusion or lateral lumbar interbody fusion with posterior screw fixation). Intraoperative, radiographic, and clinical outcomes, as well as complications, were compared between groups with ANOVA and χ2 tests. One-hundred and thirty-eight patients were included for study (PSF, n = 37; PSF-IB, n = 44; AP, n = 57). Intraoperatively, estimated blood loss was similar between groups (p = 0.171). However, the AP group had longer operative times (547.5min) compared to PSF (385.1) and PSF-IB (370.7) (p < 0.001). Additionally, fusion length was shorter in PSF-IB (11.4) compared to AP (13.6) and PSF (12.9) (p = 0.004). There were no differences between the groups in terms of change in alignment from preoperative to 2years postoperative. There were no differences in clinical outcomes. While postoperative complications were largely similar between groups, operative complications were higher in the AP group (31.6%) compared to the PSF (5.4%) and PSF-IB (9.1) groups (p < 0.001). While there were differences in intraoperative outcomes (operative time and fusion length), there were no differences in postoperative clinical or radiographic outcomes. AP fusion was associated with a higher rate of operative complications.

Effect of tonsillectomy combined with steroid pulse therapy upon IgA nephropathy depending on proteinuria status at diagnosis: a nationwide multicenter cohort study in Japan.

The effects of tonsillectomy combined with steroid pulse (TSP) therapy for IgA nephropathy (IgAN) are little known. Therefore, we examined the effects of TSP therapy on the kidney outcomes of IgAN in a large, nationwide cohort study in Japan. Between 2002 and 2004, 632 IgAN patients with ≥ 0.5g/day proteinuria at diagnosis were divided into three groups with mild (0.50-0.99g/day; n = 264), moderate (1.00-1.99g/day, n = 216), or severe (≥ 2.00g/day; n = 153). Decline in kidney function and urinary remission were compared among the three groups after TSP therapy, corticosteroid (ST) therapy, or conservative therapy during a mean follow-up of 6.2 ± 3.3years. 10.6% and 5.9% of patients in the ST and conservative therapy group underwent tonsillectomy. The rate of urinary remission at the final observation was significantly higher in the TSP therapy group than in the ST or conservative therapy groups (mild proteinuria: 64%, 43%, and 41%; moderate proteinuria: 51%, 45%, and 28%; severe proteinuria: 48%, 30%, and 22%, respectively). In contrast, the rate of a 50% increase in serum creatinine was lower in groups TSP therapy, than ST or conservative therapy (mild proteinuria: 2.1%, 10.1% and 16.7%; moderate proteinuria: 4.8%, 8.8% and 27.7%; severe proteinuria: 12.0%, 28.9% and 43.1%, respectively). In multivariate analysis, TSP therapy significantly prevented a 50% increase in serum creatinine levels compared with conservative therapy in groups with moderate and severe proteinuria (hazard ratio, 0.12 and 0.22, respectively). TSP significantly increased the rate of proteinuria disappearance and urinary remission in IgAN patients with mild-to-moderate urinary protein levels. It may also reduce the decline in kidney function in patients with moderate-to-severe urinary protein levels.

Comparison of two bundles for reducing surgical site infection in colorectal surgery: multicentre cohort study.

There is controversy regarding the maximum number of elements that can be included in a surgical site infection prevention bundle. In addition, it is unclear whether a bundle of this type can be implemented at a multicentre level. A pragmatic, multicentre cohort study was designed to analyse surgical site infection rates in elective colorectal surgery after the sequential implementation of two preventive bundle protocols. Secondary outcomes were to determine compliance with individual measures and to establish their effectiveness, duration of stay, microbiology and 30-day mortality rate. A total of 32 205 patients were included. A 50% reduction in surgical site infection was achieved after the implementation of two sequential sets of bundles: from 18.16% in the Baseline group to 10.03% with Bundle-1 and 8.19% with Bundle-2. Bundle-2 reduced superficial-surgical site infection (OR 0.74 (95% c.i. 0.58 to 0.95); P = 0.018) and deep-surgical site infection (OR 0.66 (95% c.i. 0.46 to 0.93); P = 0.018) but not organ/space-surgical site infection (OR 0.88 (95% c.i. 0.74 to 1.06); P = 0.172). Compliance increased after the addition of four measures to Bundle-2. In the multivariable analysis, for organ/space-surgical site infection, laparoscopy, oral antibiotic prophylaxis and mechanical bowel preparation were protective factors in colonic procedures, while no protective factors were found in rectal surgery. Duration of stay fell significantly over time, from 7 in the Baseline group to 6 and 5 days for Bundle-1 and Bundle-2 respectively (P < 0.001). The mortality rate fell from 1.4% in the Baseline group to 0.59% and 0.6% for Bundle-1 and Bundle-2 respectively (P < 0.001). There was an increase in Gram-positive bacteria and yeast isolation, and reduction in Gram-negative bacteria and anaerobes in organ/space-surgical site infection. The addition of measures to create a final 10-measure protocol had a cumulative protective effect on reducing surgical site infection. However, organ/space-surgical site infection did not benefit from the addition. No protective measures were found for organ/space-surgical site infection in rectal surgery. Compliance with preventive measures increased from Bundle-1 to Bundle-2.

Efficacy and Safety of Ceftazidime-Avibactam Alone versus Ceftazidime-Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort.

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07-1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14-0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting.

Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients.

Background and aimGermline BRCA1–2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients. MethodsClinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A. Results11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1–2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged > 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients. ConclusionsA remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1–2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.

Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma.

We aimed to evaluate the generalizability of retrospective single-center cohort studies on prognosis of hepatocellular carcinoma (HCC) by comparing overall survival (OS) after various treatments between a nationwide multicenter cohort and a single-center cohort of HCC patients. Patients newly diagnosed with HCC between January 2008 and December 2018 were analyzed using data from the Korean Primary Liver Cancer Registry (multicenter cohort, n=16,443), and the Asan Medical Center HCC registry (single-center cohort, n=15,655). The primary outcome, OS after initial treatment, was compared between the two cohorts for both the entire population and for subcohorts with Child-Pugh A liver function (n=2797 and n=5151, respectively) treated according to the Barcelona-Clinic-Liver-Cancer (BCLC) strategy, using Log rank test and Cox proportional hazard models. Patients of BCLC stages 0 and A (59.3% vs 35.2%) and patients who received curative treatment (42.1% vs 32.1%) were more frequently observed in the single-center cohort (Ps<0.001). Multivariable analysis revealed significant differences between the two cohorts in OS according to type of treatment: the multicenter cohort was associated with higher risk of mortality among patients who received curative (adjusted hazard ratio [95% confidence interval], 1.48 [1.39-1.59]) and non-curative (1.22 [1.17-1.27]) treatments, whereas the risk was lower in patients treated with systemic therapy (0.83 [0.74-0.92]) and best supportive care (0.85 [0.79-0.91]). Subcohort analysis also demonstrated significantly different OS between the two cohorts, with a higher risk of mortality in multicenter cohort patients who received chemoembolization (1.72 [1.48-2.00]) and ablation (1.44 [1.08-1.92]). Comparisons of single-center and multicenter cohorts of HCC patients revealed significant differences in OS according to treatment modality after adjustment for prognostic variables. Therefore, the results of retrospective single-center cohort studies of HCC treatments may not be generalizable to real-world practice.

Helicobacter pylori infection is a risk factor for constipation in patients with Parkinson's disease: A multicenter prospective cohort study

Background and AimsConstipation is one of the most common nonmotor symptoms (NMSs) of Parkinson's disease (PD). The infection rate of Helicobacter pylori (HP) is greater in PD patients. This study was a multicenter prospective cohort study in which propensity score matching (PSM) was used to determine whether HP infection was a risk factor for constipation in patients with PD. MethodsA total of 932 PD patients with 13C‐urea breath test for HP were included in the study. The PSM was estimated with the use of a nonparsimonious multivariate logistic regression model, with HP infection as the dependent variable and all the baseline characteristics as covariates. A total of 697 patients composed the study cohort, including 252 (36.2%) patients in the HP-positive (HPP) group and 445 (63.8%) patients in the HP-negative (HPN) group. Before PSM, there were differences in several of the baseline variables between the two groups. After PSM, 250 HPP patients were matched with 250 HPN patients and the standardized differences were less than 0.1 for all variables. ResultsThe present results demonstrate that HP infection is a risk factor for constipation in patients with PD [RR (95% CI) 1.412 (1.155∼1.727), P<0.001]. Subgroup analyses revealed that HP infection was both a risk factor for constipation in Hoehn-Yahr scale (1,1.5) group and Hoehn-Yahr scale (2-5) group [OR (95% CI) 1.811 (1.079∼3.038), P<0.025; OR (95% CI) 2.041 (1.177∼3.541), P<0.011]. ConclusionsThe results of our prospective cohort study suggest that Helicobacter pylori infection is a risk factor for constipation in patients with PD. Trial registrationChiCTR2300071631

COVID-19 Across Pandemic Variant Periods: The Severe Acute Respiratory Infection-Preparedness (SARI-PREP) Study.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has evolved through multiple phases in the United States, with significant differences in patient centered outcomes with improvements in hospital strain, medical countermeasures, and overall understanding of the disease. We describe how patient characteristics changed and care progressed over the various pandemic phases; we also emphasize the need for an ongoing clinical network to improve the understanding of known and novel respiratory viral diseases. To describe how patient characteristics and care evolved across the various COVID-19 pandemic periods in those hospitalized with viral severe acute respiratory infection (SARI). Severe Acute Respiratory Infection-Preparedness (SARI-PREP) is a Centers for Disease Control and Prevention Foundation-funded, Society of Critical Care Medicine Discovery-housed, longitudinal multicenter cohort study of viral pneumonia. We defined SARI patients as those hospitalized with laboratory-confirmed respiratory viral infection and an acute syndrome of fever, cough, and radiographic infiltrates or hypoxemia. We collected patient-level data including demographic characteristics, comorbidities, acute physiologic measures, serum and respiratory specimens, therapeutics, and outcomes. Outcomes were described across four pandemic variant periods based on a SARS-CoV-2 sequenced subsample: pre-Delta, Delta, Omicron BA.1, and Omicron post-BA.1. Multicenter cohort of adult patients admitted to an acute care ward or ICU from seven hospitals representing diverse geographic regions across the United States. Patients with SARI caused by infection with respiratory viruses. Eight hundred seventy-four adult patients with SARI were enrolled at seven study hospitals between March 2020 and April 2023. Most patients (780, 89%) had SARS-CoV-2 infection. Across the COVID-19 cohort, median age was 60 years (interquartile range, 48.0-71.0 yr) and 66% were male. Almost half (430, 49%) of the study population belonged to underserved communities. Most patients (76.5%) were admitted to the ICU, 52.5% received mechanical ventilation, and observed hospital mortality was 25.5%. As the pandemic progressed, we observed decreases in ICU utilization (94% to 58%), hospital length of stay (median, 26.0 to 8.5 d), and hospital mortality (32% to 12%), while the number of comorbid conditions increased. We describe increasing comorbidities but improved outcomes across pandemic variant periods, in the setting of multiple factors, including evolving care delivery, countermeasures, and viral variants. An understanding of patient-level factors may inform treatment options for subsequent variants and future novel pathogens.

Fine-grained subphenotypes in acute kidney injury populations based on deep clustering: Derivation and interpretation

BackgroundAcute kidney injury (AKI) is associated with increased mortality in critically ill patients. Due to differences in the etiology and pathophysiological mechanism, the current AKI criteria put it an embarrassment to evaluate clinical therapy and prognosis. ObjectiveWe aimed to identify subphenotypes based on routinely collected clinical data to expose the unique pathophysiologic patterns. MethodsA retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD), and a deep clustering approach was conducted to derive subphenotypes. We conducted further analysis to uncover the underlying clinical patterns and interpret the subphenotype derivation. ResultsWe studied 14,189 and 19,382 patients with AKI within 48 h of ICU admission in the two datasets, respectively. Through our approach, we identified seven distinct AKI subphenotypes with mortality heterogeneity in each cohort. These subphenotypes displayed significant variations in demographics, comorbidities, levels of laboratory measurements, and survival patterns. Notably, the subphenotypes could not be effectively characterized using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria alone. Therefore, we uncovered the unique underlying characteristics of each subphenotype through model-based interpretation. To assess the usability of the subphenotypes, we conducted an evaluation, which yielded a micro-Area Under the Receiver Operating Characteristic (AUROC) of 0.81 in the single-center cohort and 0.83 in the multi-center cohort within 48-hour of admission. ConclusionWe derived highly characteristic, interpretable, and usable AKI subphenotypes that exhibited superior prognostic values.

Endometriosis and risk of adverse pregnancy outcomes: a retrospective multicenter cohort study

To investigate: first, the association between endometriosis and preterm birth; second, the associations between endometriosis and preeclampsia, placenta previa, postpartum hemorrhage, stillbirth, and small-for-gestational-age infants (assessed by birthweight); and third, the risk of these adverse pregnancy outcomes with and without the use of medically assisted reproduction. Multicenter retrospective cohort study. 103 French maternity units. Deliveries by 368,935 women (377,338 infants) from 1999 through 2016. Endometriosis, defined as a single disease entity (endometriosis and/or ademyosis). The main outcome was the preterm birth rate (both < 37 and < 33 weeks). The secondary outcomes were rates of preeclampsia, placenta previa, postpartum hemorrhage, stillbirth, and small-for-gestational-age neonates. Women in the endometriosis group had more frequent histories of infertility before the included pregnancy (34.7 vs 5.0%, P <10-4), more hospitalizations during the pregnancy (27.4 vs. 19.8%, P <10-4), and more planned cesarean sections (14.0 vs. 8.7, P <10-4); they were more often nulliparous (51.7 vs. 43.4%, P <10-4). The prevalence of preterm birth <37 weeks was 11.1% in the endometriosis group and 7.7% in the unexposed group, and <33 weeks 3.1% and 2.2% respectively. The adjusted relative risk for confounding factors was higher in the endometriosis than the unexposed group for preterm delivery <37 weeks (1.40, 95%CI 1.18-1.67) or <33 weeks (1.53, 95%CI 1.08-2.16). For the secondary outcomes, the adjusted risk ratios for preeclampsia, placenta previa, postpartum hemorrhage, and small-for-gestational-age status <10th and < 5th percentiles were higher in the endometriosis group. The adjusted risk ratios for stillbirth and small-for-gestational-age status <3rd percentile did not differ between the two groups, and those after stratification by medically assisted reproduction for preterm birth <37 and <33 weeks did not differ statistically significantly between them for the secondary outcomes, only the risk of placenta previa was higher in the medically assisted reproduction and no-medically assisted reproduction subgroups. Pregnant women with endometriosis had higher risks of preterm birth and other poor pregnancy outcomes than women without endometriosis.

Perinatal outcomes in grand multiparous women stratified by parity- A large multicenter study

ObjectiveTo assess the effect of each additional delivery among grand multiparous (GMP) women on maternal and neonatal outcomes. MethodsA multi-center retrospective cohort study that examined maternal and neonatal outcomes of GMP women (parity 5–10, analyzed separately for each parity level) compared to a reference group of multiparous women (parity 2–4). The study population included grand multiparous women with singleton gestation who delivered in one of four university-affiliated obstetrical centers in a single geographic area, between 2003 and 2021. We excluded nulliparous, those with parity > 10 (due to small sample sizes), women with previous cesarean deliveries (CDs), multifetal gestations, and out-of-hospital deliveries. The primary outcome of this study was postpartum hemorrhage (PPH, estimated blood loss exceeding 1000 ml, and/or requiring blood product transfusion, and/or a hemoglobin drop > 3 g/Dl). Secondary outcomes included unplanned cesarean deliveries, preterm delivery, along with other adverse maternal and neonatal outcomes. Univariate analysis was followed by multivariable logistic regression. ResultsDuring the study period, 251,786 deliveries of 120,793 patients met the inclusion and exclusion criteria. Of those, 173,113 (69%) were of parity 2–4 (reference group), 27,894 (11%) were of parity five, 19,146 (8%) were of parity six, 13,115 (5%) were of parity seven, 8903 (4%) were of parity eight, 5802 (2%) were of parity nine and 3813 (2%) were of parity ten.GMP women exhibited significantly higher rates of PPH starting from parity eight. The adjusted odds ratios (aOR) were 1.19 (95 % CI: 1.06–1.34) for parity 8, 1.17 (95 % CI: 1.01–1.36) for parity 9, and 1.39 (95 % CI: 1.18–1.65) for parity 10. Additionally, they showed elevated rates of several maternal and neonatal outcomes, including placental abruption, large-for-gestational age (LGA) neonates, neonatal hypoglycemia, and neonatal seizures. Conversely, they exhibited decreased risk for other adverse maternal outcomes, including preterm deliveries, unplanned cesarean deliveries (CDs), vacuum-assisted delivery, and third- or fourth-degree perineal tears and small-for-gestational age (SGA) neonates. The associations with neonatal hypoglycemia, and neonatal seizure were correlated with the number of deliveries in a dose-dependent manner, demonstrating that each additional delivery was associated with an additional, significant impact on obstetrical complications. ConclusionOur study demonstrates that parity 8–10 is associated with a significantly increased risk of PPH. Parity level > 5 correlated with increased odds of placental abruption, LGA neonates, neonatal hypoglycemia, and neonatal seizures. However, GMP women also demonstrated a reduced likelihood of certain adverse maternal outcomes, including unplanned cesarean, preterm deliveries, vacuum-assisted deliveries, SGA neonates, and severe perineal tears. These findings highlight the importance of tailored obstetrical care for GMP women to mitigate the elevated risks associated with higher parity.

Evaluating neurocognitive outcomes in out-of-hospital cardiac arrest survivors: A comparative study of performance-based and reported measures

AimsTo (1) describe the prevalence of cognitive dysfunctions using performance-based and reported measures, and (2) explore the correlations between selected performancebased, patient-reported, and observer-reported neurocognitive outcome measures three months after hospital discharge in a population of out-of-hospital cardiac arrest (OHCA) survivors. MethodsData from 193 OHCA survivors was derived from the Danish multicenter REVIVAL cohort study. At three months, four subtests of the performance-based Delis-Kaplan Executive Function System (D-KEFS) (Trail making, Color-word interference, Verbal fluency, and Figure design), the patient-reported Behavior Rating Inventory of Executive Function − Adult (BRIEF-A), and the observer-reported 16-item Short Form (SF) Informant Questionnaire on Cognitive Decline after Cardiac Arrest (SF-16 IQCODE-CA) were collected. Spearman’s rank coefficient correlation analysis was performed to examine correlations between D-KEFS, BRIEF-A, and SF-16 IQCODECA. ResultsOverall, 21% of survivors exhibited impairment in executive functioning using the DKEFS subtest Color-word interference, while only 9% self-reported executive impairment (BRIEF-A) and 7% of relatives reported cognitive decline (SF-16 IQCODECA) in survivors at three months post-arrest. All correlations between D-KEFS, BRIEFA, and SF-16 IQCODE-CA were negligible to low. ConclusionThe results of this REVIVAL substudy suggest that although the performance-based and reported measures did not correlate, dual neurocognitive screening tools containing both a self-reported and an informant-reported version may have the potential to detect executive discrepancies in the return to everyday life and guide targeted neurorehabilitation after OHCA.

The Impact of Fibroblast Growth Factor Receptor Alterations in Clinical Outcomes of Patients With Advanced Urothelial Carcinoma: Real-World Data From a Latin American Population

IntroductionFibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes. Patients and methodsA multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics. ResultsIn total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049). ConclusionsThis is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort.

Les reconnaissances en maladie professionnelle lors du suivi de la cohorte ARDCO

Questions concerning under-reporting of occupational diseases (OD) linked to asbestos exposure are regularly voiced in France. Monitoring of the French multicenter Asbestos-Related Disease Cohort (ARDCO), which ensures post-occupational medical surveillance of subjects having been exposed to asbestos, provides information on (1) the medico-legal steps taken following screening by computed tomography (CT) for benign thoracic diseases, and (2) recognition of OD as a causal factor in malignant diseases. OD recognition -and possible compensation- was analyzed in July 2021 among 13,289 volunteers in the cohort recruited between 2003 and 2005. Fifteen percent of the subjects in the cohort were found to have at least one recognized asbestos-related OD (78.2% benign pleural disease, 10.3% asbestosis, 14.2% lung cancer, and 6.0% mesothelioma). Only 58% of pleural plaques reported by the radiologist who performed the CT resulted in their recognition as ODs. On a parallel track, 88.7% of the mesotheliomas identified based on French National health insurance data and 46.9% of lung cancers were recognized as ODs. This study confirms the feasibility of a system designed to facilitate recognition, leading to possible compensation, of asbestos-related occupational diseases. The system could be improved by better training of the medical actors involved.