Multicenter Observational Cohort Study Research Articles

Renal protective effect of metformin in type 2 diabetes patients.

Inhibiting the development and progression of diabetic kidney disease (DKD) is an important issue, but the renoprotective effect of metformin is still controversial. To assess the renoprotective effect of metformin in patients with type 2 diabetes. This retrospective observational multicenter cohort study included 316,693 patients with type 2 diabetes from seven hospital. After age, gender, medical year, baseline estimated glomerular filtration rate (eGFR), urine protein (dipstick), glycated hemoglobin (HbA1C) and propensity score matching; a total of 13,096 metformin and 13,096 non-metformin patients were included. The main results were doubling of serum creatinine, eGFR ≤ 15 mL/min/1.73 m2 and end stage kidney disease (ESKD). After conducting a multivariable logistic regression analysis on the variables, the metformin group was revealed to have better renal outcomes than non-metformin group, including a lower incidence of doubling of serum creatinine (hazard ratio [HR], 0.71; 95% CI, 0.65-0.77), eGFR ≤ 15 mL/min/1.73 m2 (HR 0.61; 95% CI 0.53-0.71), and ESKD (HR 0.55; 95% CI 0.47-0.66). The subgroup analyses revealed a consistent renoprotective effect across patients with various renal functions. Furthermore, when considering factors such as age, sex, comorbidities, and medications in subgroup analyses, it consistently showed that the metformin group experienced a slower deterioration in renal function across nearly all patient subgroups. Metformin decreased the risk of renal function deterioration.

Health Care Access, Socioeconomic Status, and Acute Kidney Injury Outcomes: A Prospective National Study

Acute kidney injury (AKI) incidence and outcome in Kuwait are unknown. Moreover, non-Kuwaitis, who represent 66% of the population, have lower income, and their access to public health services is restricted compared with Kuwaitis who have free full access. Observational prospective multicenter cohort study. Adult inpatients with AKI in 7 public hospitals from January 1 to December 31,2021. AKI identified using Kidney Disease: Improving Global Outcomes serum creatinine-based criteria. For hospitalized patients with AKI, the outcomes included 30-day outcomes of mortality, need for dialysis, kidney recovery rates, and differences in outcomes between Kuwaitis and non-Kuwaitis. A backward stepwise multiple logistic regression analysis was performed to assess possible independent risk factors for the outcomes. We recruited 3,744 patients (mean age: 63 years; mean baseline estimated glomerular filtration rate [eGFR]: 66.7mL/min; non-Kuwaitis: 42.3%), representing 3.2% of hospitalizations and 19.5% of intensive care unit (ICU) admissions. Non-Kuwaitis were significantly younger (57.6 vs 66.9 years), with higher baseline eGFR (73.1 vs. 62mL/min), more frequent community acquired AKI (53.8% vs 46.7%), and AKI in summer (34.7% vs 26.9%). Dialysis was provided to 33.5% of patients, with a higher need for non-Kuwaitis (35.5% vs 32.1%). At 30 days, 34.4% of patients died, representing 24.8% of hospital mortality and 59.8% of ICU mortality. No differences in mortality or kidney recovery were noted between Kuwaitis and non-Kuwaitis. Low eGFR did not affect the mortality rate. Observational nature and short follow-up period of 30 days only. AKI was associated with high dialysis need and mortality. Non-Kuwaitis accounted for less cases despite representing 66% of the population because they were younger with higher baseline eGFR and fewer comorbid conditions. Non-Kuwaitis had higher rates of community acquired AKI and AKI in summer and a higher need for dialysis but had similar mortality and complete kidney recovery rates.

Usefulness of the one-step technique in functional end-to-end anastomosis for colonic surgery: results of a prospective multicentre cohort study from the Japanese KYCC group.

Although functional end-to-end anastomosis (FEEA) using a stapler in the colorectal field has been recognised worldwide, the technique varies by surgeon, and the safety of anastomosis using different techniques is unknown. This multicentre prospective observational cohort study was conducted by the KYCC Study Group in Yokohama, Japan, and included patients who underwent colonic resection at seven centres between April 2020 and March 2022. This study compared the incidence of surgery-related abdominal complications (SAC: anastomotic leakage [AL], anastomotic bleeding, intra-abdominal abscess, enteritis, ileus, surgical site infection, and other abdominal complications) between two different methods of FEEA (one-step [OS] method: simultaneous anastomosis and bowel resection; two-step [TS] method: anastomosis after bowel resection). Complications of Clavien-Dindo classification grade2 or higher were assessed. Among 293 eligible cases, the OS and TS methods were used in 194 (66.2%) and 99 (33.8%) patients, respectively. The baseline characteristics were similar between the groups. The OS method used fewer staplers (three vs. four staplers, p < 0.00001). There were no significant differences in SAC rate between the OS (19.1%) and the TS (16.2%) groups (p = 0.44). The OS group had four cases (2.1%) of AL (two patients; grade3, two patients; grade2) while the TS group had one case (1.0%) of grade2 AL (p = 0.67). Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 3.95; p < 0.00001), an open surgical approach (OR 2.36; p = 0.03), and longer operative duration (OR,2.79; p = 0.002) were independent predictors of complications, whereas the OS method was not an independent predictor (OR 1.17; p = 0.66). The OS and the TS technique for stapled colonic anastomosis in a FEEA had a similar postoperative complication rate. UMIN000039902 (registration date 23 March 2020).

Mitochondrial oxygen tension in critically ill patients receiving red blood cell transfusions: a multicenter observational cohort study

PurposeCurrently, there is no marker of efficacy of red blood cell (RBC) transfusion. This study describes the impact of RBC transfusion on mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in critically ill patients with anemia.MethodsCritically ill patients with a hemoglobin concentration < 10 g/dL, for whom a single RBC unit had been ordered, were included. MitoPO2 was measured with the COMET device immediately before RBC transfusion, 0.5 h, 1 h, 3 h, and 24 h after RBC transfusion. MitoVO2 was calculated from dynamic mitoPO2 measurements during cessation of local oxygen supply.ResultsSixty-three patients participated, median age 64.0 (interquartile range (IQR) 52.3–72.8) years, median hemoglobin concentration before transfusion 7.4 (IQR 7.1–7.7) g/dL. Median mitoPO2 values were 55.0 (IQR 49.6–63.0) mmHg before RBC transfusion, 51.0 (IQR 41.5–61.2) directly after and 67.3 (IQR 41.6–83.7) at 24 h after RBC transfusion. Median mitoVO2 values were 3.3 (IQR 2.1–5.9) mmHg/s before RBC transfusion, 3.7 (IQR 2.0–5.1) mmHg/s directly after, and 3.1 (IQR 2.5–4.8) mmHg/s 24 h after RBC transfusion. In the higher Hb concentration group (> 7 g/dL), we saw a dissociation of the effect of RBC transfusion on mitoPO2 versus on mitoVO2 values. MitoPO2 and mitoVO2 values were not associated with commonly used parameters of tissue perfusion and oxygenation.ConclusionRBC transfusion did not alter mitoPO2 and mitoVO2 in critically ill patients with anemia. MitoPO2 and mitoVO2 values were not notably associated with Hb concentrations, parameters of severity of illness and markers of tissue perfusion or oxygenation. Given the high baseline value, it cannot be excluded nor confirmed whether RBC can improve low mitoPO2.Trial registration number NCT03092297 (registered 27 March 2017)

Associations of early changes in lung ultrasound aeration scores and mortality in invasively ventilated patients: a post hoc analysis

BackgroundLung ultrasound (LUS) in an emerging technique used in the intensive care unit (ICU). The derivative LUS aeration score has been shown to have associations with mortality in invasively ventilated patients. This study assessed the predictive value of baseline and early changes in LUS aeration scores in critically ill invasively ventilated patients with and without ARDS (Acute Respiratory Distress Syndrome) on 30- and 90-day mortality.MethodsThis is a post hoc analysis of a multicenter prospective observational cohort study, which included patients admitted to the ICU with an expected duration of ventilation for at least 24 h. We restricted participation to patients who underwent a 12-region LUS exam at baseline and had the primary endpoint (30-day mortality) available. Logistic regression was used to analyze the primary and secondary endpoints. The analysis was performed for the complete patient cohort and for predefined subgroups (ARDS and no ARDS).ResultsA total of 442 patients were included, of whom 245 had a second LUS exam. The baseline LUS aeration score was not associated with mortality (1.02 (95% CI: 0.99 – 1.06), p = 0.143). This finding was not different in patients with and in patients without ARDS. Early deterioration of the LUS score was associated with mortality (2.09 (95% CI: 1.01 – 4.3), p = 0.046) in patients without ARDS, but not in patients with ARDS or in the complete patient cohort.ConclusionIn this cohort of critically ill invasively ventilated patients, the baseline LUS aeration score was not associated with 30- and 90-day mortality. An early change in the LUS aeration score was associated with mortality, but only in patients without ARDS.Trial registrationClinicalTrials.gov, ID NCT04482621.

O-252 Cumulative live birth rates (CLBR) in in vitro fertilization per oocyte used, embryo transferred, and embryo transfer impair with increasing female body mass index (BMI)

Abstract Study question Does the number of oocytes used, embryos transferred, or embryo transfers to achieve specific cumulative live birth rates differ according to female body mass index? Summary answer The greater the female BMI, the higher the number of oocytes, embryos and embryo transfers needed to achieve a liveborn, indicating a lower reproductive potential. What is known already The negative impact of high female BMI on in vitro fertilization (IVF) cycles has been extensively described in the medical literature, although there is no clear agreement on the potential role of oocytes, embryos, and endometrial receptivity on these results. However, the clinical outcome is commonly assessed per embryo transfer in isolated cycles and less frequently in cumulative cycles from the same cohort of oocytes. The number of oocytes or embryos needed to reach specific clinical goals has been never estimated in comparison to women with other BMIs, which gives a relevant multicycle overview of reproductive outcomes. Study design, size, duration This is a multicenter retrospective observational cohort study including a total of 31,289 women undergoing IVF with known BMI and 35,430 embryo transfers performed in 15 IVIRMA centers in Spain, from January 1, 2017, to October 1, 2023 with known outcome. Patients were grouped as Underweight (U, BMI&amp;lt;18.5 kg/m2), Normoweight (N, BMI 18.5-&amp;lt;25 kg/m2), Overweight (Ov, BMI 25-&amp;lt;30 kg/m2), and Obese (Ob, BMI≥30 kg/m2). Participants/materials, setting, methods IVF-ICSI cycles with autologous oocytes and partner’s sperm were analyzed according to female BMI. CLBR per oocyte used, embryos replaced, and embryo transfers in consecutive treatments until reaching live birth or abandon were calculated by survival curve analyses with Kaplan-Meier’s methods estimating hazard ratios (HR), and BMI groups compared by with Log-Rank test. Outcomes per embryo transfer/completed cycle and descriptives were compared by chi square tests, and ANOVA where appropriate. Main results and the role of chance Mean women’s age was 37.6years, 95%CI(37.5-37.6), 36.9 years95%CI(36.7-37.1), 37.7years95%CI(37.6-37.8), and 37.2years95%CI(37.0-37.4) for N, U, Ov, and OB respectively. Mean stimulation days and serum progesterone concentrations the day of hCG administration were comparable. Estradiol on triggering day was statistically higher(p &amp;lt; 0.05) on U group, 2073pg/ml95%CI(2008-2138), compared to the other groups, N 1942pg/ml95%CI(1926-1957), Ov 1840pg/ml95%CI(1808-1872), and Ob 1789pg/ml 95%CI(1742-1835). Number of aspirated oocytes was higher on Ob 9.47,95%CI(9.23-9.71), compared with N 9.1,95%CI(9.02-9.17),p&amp;lt;0.05. LBR per embryo transfer was 35.0%95%CI(32.9-37.3) for U, 33.3%95%CI(32.7-33.9) for N, 32.13%95%CI(30.9-33.4) for Ov ad 28.3%95%CI(26.6-30.1) for Ob, p &amp;lt; 0.001. LBR per completed IVF-ICSI cycle (until reaching live birth or using all embryos) was 41.8%95%CI(69.7-43.9) for U, 40.6%95%CI(40.0-41.18) for N, 39.50%95%CI(38.4-40.6) for Ov, and 39.6%95%CI(37.9-41.37) for Ob, being statistically comparable. Using N as a reference group, HR were 1.07,95%CI(0.98-1.17) for U, 0.98,95%CI(0.93-1.03) for Ov, and 0.90,95%CI(0.84-0.98) for Ob, p-value=0.011, being Ob significantly different compared to N. Regarding HR per embryo transfer, 0.96,95%CI(0.82-1.13) for U, 0.87,95%CI(0.79-0.96) for Ov and 0.76,95%CI(0.66-0.89) for Ob, being statistically different Ov (p = 0.0055) and OB (p &amp;lt; 0.001) from N. With the total number of embryos transferred, HR were better than N in U group, 1.11,95%CI(1.02-1.20), p = 0.0192 and significantly worse in Ov and Ob, 0.91,95%CI(0.87-0.96) and 0.85,95%CI(0.79-0.92), p &amp;lt; 0.001 on both. Limitations, reasons for caution Despite the huge sample of patients included and the statistical approach used, the retrospective design of the study represents its main limitation, thus needing to interpret the findings with caution. Wider implications of the findings IVF-ICSI cycles in women high BMI are less efficient than in normoweight women since a greater number of oocytes, embryos and embryo transfers are needed to reach similar CLBRs. This finding highlights again the advice of initiating IVF with an adequate female body weight. 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 &amp;lt; 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 (&amp;lt;2,500 g), 0.710 (0.463-1.088) p = 0.116 for very low birth weight (&amp;lt;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

Safety and effectiveness of disease-modifying therapies after switching from natalizumab

Introduction: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. Objective: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. Methods: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. Results: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). Conclusion: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity.

Cost-effectiveness and safety of continuous pulse oximetry for management of undiagnosed obstructive sleep apnea in bariatric surgery: a nationwide cohort study

BackgroundUndetected obstructive sleep apnea (OSA) is highly prevalent in patients undergoing bariatric surgery and increases perioperative risks. Screening for OSA using preoperative polygraphy (PG) with subsequent continuous positive airway pressure (CPAP) is costly and time-consuming. Postoperative continuous pulse oximetry (CPOX) is less invasive, and is hypothesized to be a safe and cost-effective alternative. ObjectivesThis nationwide multicenter prospective observational cohort study compared CPOX monitoring with OSA-screening using PG. SettingHigh-volume bariatric centers. MethodsPatients were either postoperatively monitored using CPOX without preoperative OSA-screening, or underwent preoperative PG and CPAP treatment when OSA was diagnosed. Cohort placement was based on local hospital protocols. Cost-effectiveness was analyzed using quality adjusted life years (QALYs) and healthcare costs. Surgical outcomes were also analyzed. Propensity score matching was used in sensitivity analyses. ResultsA total of 1390 patients were included. QALYs were similar between groups at baseline and 1-year postoperatively. Postoperative complications, intensive care unit (ICU)-admissions and admissions, particularly OSA-related, did not differ between groups. Mean costs per patient/year in the CPOX group was €3094 versus €3680 in the PG group; mean difference €−586 (95% CI €−933–€−242). Following propensity score matching, 1090 of 1390 included patients remained, and similar findings for cost-effectiveness, complications, and ICU admissions were observed. ConclusionCPOX monitoring without preoperative OSA-screening was not associated with higher complication or readmission rates compared to PG. CPOX resulted in lower costs from a healthcare perspective and can therefore be considered a cost-effective alternative to routine OSA-screening in patients undergoing bariatric surgery.

Acute Clinical Events Identified as Relapses With Stable Magnetic Resonance Imaging in Multiple Sclerosis

Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development. To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI). This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection. Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise. Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated. Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs. The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Preliminary results from the Polish Infective Endocarditis Registry (POL-ENDO): Time to change clinical practice?

Infective endocarditis (IE) is a severe valvular disease associated with high morbidity and mortality. This preliminary study aimed to evaluate patient profiles and treatment outcomes of IE in Poland and compare them with European IE characteristics. We conducted a prospective multicenter observational cohort study - the POL-ENDO registry - in IE patients from 134 hospitals in Poland recruited between August 2022 and August 2023. We evaluated demographic, clinical, imaging, and treatment outcome data. A comparison of the Polish patients with those assessed in the EURO-ENDO registry between January 2016 and March 2018 was performed. Of a total of 880 IE patients, 622 were male (70.7%). The POL-ENDO participants were older (61.4 [16.7] years vs. 59.25 [18.03] years; P = 0.001). Native-valve IE occurred more often in Poland (82.3% vs. 56.6%; P <0.001). Transthoracic echocardiography was performed more frequently in Poland (93.6% vs. 89.8%; P <0.001). New imaging techniques (computed tomography/magnetic resonance imaging/positron emission tomography/single-photon emission computed tomography) were less frequently used in Poland (computed tomography: 41.3% vs. 53.2%; P <0.001; magnetic resonance imaging: 6.4% vs. 18.7%; P <0.001). Heart failure occurred more often in Poland as an in-hospital complication (31.4% vs. 14.1%; P <0.001). Surgical treatment was less frequently performed in Poland (36.9% vs. 51.2%; P <0.001). In-hospital mortality was higher in Poland (21% vs. 17%; P = 0.008). Polish IE patients were significantly older and had more comorbidities. New imaging techniques are less frequently used in Poland. Echocardiography was performed more frequently in Poland as the diagnostic mainstay. Surgical treatment was significantly less frequent in Poland. In-hospital mortality in Poland is higher.

Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024

BackgroundA notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients.MethodsThe current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI).ResultsDuring the study period (November 2022–January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21).ConclusionsCritically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.

Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years.

Neurodevelopmental effects of fetal antiseizure medication (ASM) exposure on creativity and executive functions are poorly understood. We previously found fetal valproate exposure to adversely affect measures of creativity and executive functions. In this study, we examine fetal exposure of newer ASMs on these functions in children of women with epilepsy (WWE) compared with children of healthy women (HW). The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational cohort study of WWE and HW enrolled in pregnancy and their offsprings. This report examines blindly assessed creativity and executive functions in 4.5-year-old children of WWE vs HW. In addition, exposure-dependent ASM effects during the third trimester were examined in children of WWE, using a ratio of maximum observed ASM concentrations and ratio of defined daily dose (ratio DDD). For polytherapy, ratios were summed across ASMs. Linear regression models adjusted for multiple potential confounding factors were conducted for all analyses. The primary outcome for 4.5-year-old children was the Torrance Test of Creative Thinking-Figural Creativity Index. Secondary outcomes included the Global Executive Composite Score from the Behavior Rating Inventory of Executive Function-Preschool Version and subscales and other indexes of both measures. The primary analysis included 251 children of WWE and 73 of HW. No differences in creativity or executive function were found between children of WWE vs HW. No ASM exposure-dependent effects were found for the creativity measures, but exposure-dependent effects for executive function were present for ratio ASM concentration and ratio DDD. Our findings at 4.5 years show no differences in creative thinking between children of WWE vs HW (-3.2 [-9.0 to 2.7], p = 0.286) or associations with fetal exposure to ASMs (-2.6 [-11.0 to 5.7], p = 0.530). Secondary analyses revealed fetal exposure-dependent effects for executive function in children of WWE (7.0 [2.9-11.2], p = 0.001), which are most marked for levetiracetam (12.9 [4.2-21.6], p = 0.004). Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose. The study is registered at ClinicalTrials.gov as NCT01730170.

Real-life efficacy of immunotherapy for Sézary syndrome: a multicenter observational cohort study

Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p=0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p=0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p=0.013). Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.

Male breast cancer: a multicenter study to provide a guide for proper management.

To offer an extensive retrospective experience on the management of male breast cancer. A multicenter retrospective observational cohort study was conducted, including male patients diagnosed with breast cancer (invasive or in situ) in 12 Italian breast units from January 1975 to December 2019. Patients aged 18years or older were assessed for eligibility. Exclusion criteria were metastatic cancer at diagnosis, previous cancer(s), received neoadjuvant treatment, incomplete data on (neo) adjuvant treatment(s), and/or follow-up data. Data on radiological examinations, demographic characteristics, risk factors, histological features, receptor status, treatments, and follow-up were collected. In a series of 671 male patients with breast cancer assessed for eligibility, 403 (28 in situ and 375 invasive neoplasms) were included in the study. All included patients underwent surgery. The median age at surgery was 63.8years (IQR 56.1-72.1). In 68% of cases, patients underwent echography, and in 55.1%, a mammography. Most patients were ER and PR positive (63.8%), HER2 negative (80.4%), with high (≥ 20%) Ki67 values (61.3%), and luminal B subtype (51.1%). The 10-year overall survival was 73.6% (95% CI 67.0-79.1) for invasive breast cancer and 90% (95% CI 65.6-97.4) for in situ breast cancer. In patients with invasive breast cancer, at univariable analysis, having a G3 tumor (vs. G1), pT2/3/4 (vs. pT1), pN2/3 (vs. pN0), luminal B subtype with Ki67 ≥ 20% (vs. Luminal A), were significantly associated with a higher risk of death. In multivariable analyses, pT2/3/4 (vs. pT1) remained significantly associated with a higher risk of death (HR 3.14, 95% CI 1.83-5.39), and having a HER2 positive or a triple-negative subtype (vs. Luminal A) was also significantly associated with a higher risk of mortality (HR 4.76, 95% CI 1.26-18.1). Male breast cancer is a rare disease, the better understanding of which is necessary for a more effective diagnostic and therapeutic approach.

Exploring Health-Related Quality of Life in Children With Hypertrophic Cardiomyopathy and Relationship to Physical Activity.

Hypertrophic cardiomyopathy is a burdensome condition that inflicts both physical and psychological impairment on those with the disease, negatively impacting health-related quality of life (HRQoL). Given the abundance of evidence suggesting a role of physical activity (PA) in modulating HRQoL in healthy populations of children, we sought to determine the relationship between HRQoL and PA in children diagnosed with hypertrophic cardiomyopathy. A multicenter prospective observational cohort study was conducted, with patients with hypertrophic cardiomyopathy aged 10 to 19 years being provided a wrist-worn activity tracker (Fitbit Charge HR) to wear for 14 days. Patients self-reported on Pediatric Quality of Life 4.0 quality of life inventory items, which were associated with PA metrics following covariate adjustment using linear regression. A total of 56 participants were recruited to the study. The median age at enrollment was 15.5 years (interquartile range, 13.8-16.8), and 16 out of 56 (29%) of the cohort were girls. The cohort reported decreased metrics of physical, psychosocial, and total summary scores compared with health reference populations, with scores comparable with that of published populations with chronic disease. Increased physical HRQoL scores were significantly associated with increased daily steps taken, distance traveled, and flights of stairs climbed. These results show that impaired PA correlates with reduced HRQoL in children with hypertrophic cardiomyopathy, suggesting PA may partially mediate HRQoL in this population.

Does surgery affect the neurodevelopmental outcome of moderate laryngomalacia?

BackgroundModerate laryngomalacia lies in the grey zone where the parents and treating team might hesitate to decide the treatment plan for the child. Neurodevelopmental assessment of the child was neither assessed nor incorporated in surgical decision-making in the past. ObjectivesTo evaluate the neurodevelopmental outcome of moderate laryngomalacia treatment strategies (surgery versus conservative). MethodsWe conducted an observational multicentric cohort study. We compared two groups of patients according to their moderate laryngomalacia treatment strategy: surgical treatment and no treatment. The neurodevelopmental outcome was assessed by Griffiths-III developmental scales. ResultsA total of 150 children were diagnosed with moderate laryngomalacia of which 56 were successfully treated with surgery and 94 improved without intervention. The median Griffiths-III developmental quotients (DQs) of subscales A, B, C, E, and general development were significantly higher in the surgically treated group compared to conservatively treated ones. ConclusionUntreated moderate laryngomalacia cases have worse neurodevelopmental outcomes than surgically treated cases.

Differentiation between viral and autoimmune limbic encephalitis: a prospective cohort study with development and validation of a diagnostic model.

Distinguishing between viral encephalitis (VE) and autoimmune limbic encephalitis (ALE) presents a clinical challenge due to the overlap in symptoms. We aimed to develop and validate a diagnostic prediction model to differentiate VE and ALE. A prospective observational multicentre cohort study, which continuously enrolled patients diagnosed with either ALE or VE from October 2011 to April 2023. The demographic data, clinical features, and laboratory test results were collected and subjected to logistic regression analyses. The model was displayed as a web-based nomogram and then modified into a scored prediction tool. Model performance was assessed in both derivation and external validation cohorts. A total of 2423 individuals were recruited, and 1001 (496 VE, 505 ALE) patients were included. Based on the derivation cohort (389 VE, 388 ALE), the model was developed with eight variables including age at onset, acuity, fever, headache, nausea/vomiting, psychiatric or memory complaints, status epilepticus, and CSF white blood cell count. The model showed good discrimination and calibration in both derivation (AUC 0.890; 0.868-0.913) and external validation (107 VE, 117 ALE, AUC 0.872; 0.827-0.917) cohorts. The scored prediction tool had a total point that ranged from - 4 to 10 also showing good discrimination and calibration in both derivation (AUC 0.885, 0.863-0.908) and external validation (AUC 0.868, 0.823-0.913) cohorts. The prediction model provides a reliable and user-friendly tool for differentiating between the VE and ALE, which would benefit early diagnosis and appropriate treatment and alleviate economic burdens on both patients and society.

Is the sFlt-1/PlGF ratio efficient in predicting adverse neonatal outcomes in small-for-gestational-age newborns? A prospective observational multicenter cohort study.

Fetuses with growth abnormalities are at an increased risk of adverse neonatal outcomes. The aim of this study was to investigate if placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), or the sFlt-1/PlGF ratio were efficient predictive factors of adverse neonatal outcomes in small-for-gestational-age (SGA) newborns. A prospective observational multicenter cohort study was performed between 2020 and 2023. At the time of the SGA fetus diagnosis, serum angiogenic biomarker measurements were performed. The primary outcome was an adverse neonatal outcome, diagnosed in the case of any of the following: <34 weeks of gestation: mechanical ventilation, sepsis, necrotizing enterocolitis, intraventricular hemorrhage grade III or IV, and neonatal death before discharge; ≥34 weeks of gestation: Neonatal Intensive Care Unit hospitalization, mechanical ventilation, continuous positive airway pressure, sepsis, necrotizing enterocolitis, intraventricular hemorrhage grade III or IV, and neonatal death before discharge. In total, 192 women who delivered SGA newborns were included in the study. The serum concentrations of PlGF were lower, leading to a higher sFlt-1/PlGF ratio in the adverse outcome group. No significant differences in sFlt-1 levels were observed between the groups. Both PlGF and sFlt-1 had a moderate correlation with adverse neonatal outcomes (PlGF: R - 0.5, p < 0.001; sFlt-1: 0.5, p < 0.001). The sFlt-1/PlGF ratio showed a correlation of 0.6 (p < 0.001) with adverse outcomes. The uterine artery pulsatility index (PI) and the sFlt-1/PlGF ratio were identified as the only independent risk factors for adverse outcomes. An sFlt-1/PlGF ratio of 19.1 exhibited high sensitivity (85.1%) but low specificity (35.9%) in predicting adverse outcomes and had the strongest correlation with them. This ratio allowed the risk of adverse outcomes to be assessed as low with approximately 80% certainty. The sFlt-1/PlGF ratio seems to be an efficient predictive tool in adverse outcome risk assessment. More studies on large cohorts of SGA-complicated pregnancies with and without preeclampsia are needed to develop an optimal and detailed formula for the risk assessment of adverse outcomes in SGA newborns.

British Axial Spondyloarthritis Inception Cohort (BAxSIC): a protocol for a multicentre real-world observational cohort study of early axial spondyloarthritis.

Timely diagnosis remains a challenge in axial SpA (axSpA). In addition, data are scarce on the impact of diagnostic delay and disease progression in affected individuals. The British Axial Spondyloarthritis Inception Cohort (BAxSIC) study aims to investigate the impact of newly diagnosed axSpA, the natural history of the disease and the effect of diagnostic delay on disease outcomes. BAxSIC is a prospective, multicentre, observational study. Eligible participants are adults (≥16 years of age), with a physician-confirmed diagnosis of axSpA in the 6 months prior to study entry, recruited from secondary and tertiary rheumatology centres in the UK. Participants will be followed up for 3 years, with in-person visits at baseline and 24 months. In addition, patient self-reported assessments will be recorded remotely via the online electronic case report form (eCRF) at 6, 12, 18, 30 and 36 months. The first patient was enrolled in BAxSIC in June 2023. Recruitment is currently ongoing and is planned to end in June 2026. Initial results will be available in 2027. Since opening, the trial has undergone two protocol amendments. The BAxSIC study is the first inception cohort designed to investigate the impact of diagnostic delay on clinical presentation and long-term functional outcomes in patients with axSpA in the UK. With an innovative, patient-led virtual longitudinal data collection model, data generated from this study will help inform and improve the care of people newly diagnosed with axSpA. ClinicalTrials.gov (http://clinicaltrials.gov), NCT05676775.