Mixed Cohorts Research Articles

Efficacy of Gonadotropin Treatment for Induction of Spermatogenesis in Men With Pathologic Gonadotropin Deficiency: A Meta-Analysis.

Hypogonadotropic hypogonadism (HH) is a treatable cause of nonobstructive azoospermic male infertility. Gonadotropin treatment can successfully induce spermatogenesis in most patients, although comprehensive quantitative summary data on spermatogenic outcomes like those required to induce pregnancy is lacking in the literature. Systematic review and meta-analysis of outcomes related to male reproductive function following gonadotropin treatment. Our search strategy identified 41 studies encompassing 1673 patients with a mean age of 25 (± 5) years. Average sperm concentration achieved after a median of 18 months of gonadotropin treatment was 11.6 M/mL of ejaculate (95% CI 8.4-14.9). Sperm concentrations > 0, > 1, > 5, > 10 and > 20 M/mL were achieved by 78%, 55%, 36%, 24% and 15% of patients, respectively. Mean sperm output and the proportion of patients achieving all sperm thresholds were significantly greater following combined hCG/FSH treatment compared with hCG monotherapy. When compared by diagnosis, patients with congenital HH (CHH) had significantly lower mean sperm output compared with patients with hypopituitarism or mixed patient cohorts that did not differentiate between CHH and hypopituitarism. Treatment-related increases in testosterone and testicular volume (TV) were not different between hCG and combined hCG/FSH treated patients, although increases in TV were lower in men with CHH compared with those with hypopituitarism. Gonadotropin treatment successfully induced spermatogenesis in most men with pathological gonadotropin deficiency. Sperm outputs more consistent with those typically needed to induce a natural pregnancy were less commonly achieved. Despite similar effects on serum testosterone and TV, combined hCG/FSH appeared more efficacious than hCG alone at inducing spermatogenesis.

Repeat Faecal Immunochemical Testing for Colorectal Cancer Detection in Symptomatic and Screening Patients: A Systematic Review and Meta-Analysis.

Faecal immunochemical testing (FIT) is widely used in bowel screening programmes and assessing symptomatic patients for suspected colorectal cancer (CRC). The evidence for single test performance of FIT in both settings is considerable; however, the use of a repeat test to increase sensitivity remains uncertain. We aimed to review what increase in test positivity would be generated by additional FITs, whether a repeated FIT detects previously missed CRC and advanced colorectal neoplasia (ACRN), and to estimate the sensitivity of double-FIT strategies to diagnose CRC and ACRN. A systematic search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was performed using key search terms. Studies reporting the use of more than one FIT in the same screening round or planned assessment of a single symptomatic patient episode were included. Studies were categorised by the reported study population into asymptomatic, mixed (cohorts of combined asymptomatic, symptomatic, or high-risk surveillance), or symptomatic cohorts. A total of 68 studies were included for analysis (39 asymptomatic, 21 mixed, 7 symptomatic, and 1 study with discrete asymptomatic and symptomatic data). At a threshold of 10 µg Hb/g, the two-test positivity ranged between 8.1 and 34.5%, with an increase from the second test of 3-9.2 percentage points. Four out of five studies comparing one versus two tests for diagnosing CRC at 10 µg Hb/g identified additional cases with the second test, with a minimum of 50% reduction in missed CRC. At a threshold of 20 µg Hb/g, the second test increased the positivity by 1.3-6.7 percentage points, with a two-test positivity of between 5.1 and 25.0%. Using a threshold of 20 µg Hb/g, five out of seven studies had a 25% reduction in missed CRC. A meta-analysis estimated the double-FIT sensitivity at 10 µg Hb/g for CRC in mixed-risk and symptomatic cohorts to be 94% and 98%, respectively. Repeated use of FIT helps to diagnose more cases of CRC with a moderate increase in positivity. A double-FIT strategy at 10 µg Hb/g in mixed and symptomatic cohorts has a very high sensitivity for CRC.

Evaluating Return to Sports After Surgical Treatment of Unstable Osteochondritis Dissecans of the Knee: A Systematic Review.

Although the incidence of osteochondritis dissecans (OCD) of the knee may be low, an overview and comparison of sports-related outcomes with current surgical management techniques are needed. To summarize the available evidence regarding outcomes for different surgical treatment options for unstable OCD of the knee in both skeletally mature and immature patients by calculating the return to sports (RTS) rate, the mean RTS time, and other sports-related postoperative outcome measures. Systematic review; Level of evidence, 4. A systematic review of studies on RTS after surgical correction of unstable OCD within the knee was conducted utilizing PubMed, Embase, and the Cochrane databases. Included were studies discussing the treatment of unstable OCD with minimum 1-year follow-up outcomes. Multivariate analysis was used to compare studies grouped together based on RTS and skeletal maturity. Of 2229 articles, 6 studies (197 patients; 198 knees) met the inclusion criteria and were included in our analysis. The percentage of patients who returned to the previous level of sport ranged from 52% to 100%; those returning to any level of sport ranged from 87% to 100%. Clinical outcomes did not differ between patients with open versus closed physes. Osteochondral Autograft Transfer System (OATS) procedures had a 100% RTS rate across several studies with skeletally mature and mixed cohorts, and microfracture had the lowest overall RTS rate (52%). For skeletally immature patients, all examined studies that utilized either open or arthroscopic reduction and internal fixation, 77% and 78%, respectively, had acceptable RTS rates. Arthroscopic fixation had a higher rate of revision surgery in both skeletally mature and immature patients. Our analysis indicated that the treatment of unstable OCD lesions using the OATS technique demonstrated high RTS rates across several studies, while microfracture alone exhibited the lowest RTS rate. Both arthroscopic and open internal fixation utilizing bioabsorbable screws yielded satisfactory RTS rates for juvenile patients with OCD.

O-311 Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis

Abstract Study question What is the prevalence of infertility defined by azoospermia, failure to achieve paternity or the usage of cryosperm after oncological treatments in testicular cancer? Summary answer The overall prevalence of infertility (95% CI) is 14% (9-21%) after all therapy types and 4% (2-10%) in a pooled subgroup of good-prognosis patients. What is known already Testicular cancer is the most common solid tumor among young men in the reproductive phase between 15 and 45 years. More than 95% of the patients become long-term survivors and up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. Most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last twenty years. Thus, this very first meta-analysis in a large pooled study population of patients functions as the best approximation of fertility prognosis so far. Study design, size, duration The systematic review and meta-analysis is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. It was performed on all published studies since 2000 that have reported the prevalence of azoospermia, the failure to achieve a pregnancy over 12 months of regular unprotected sexual intercourse or the usage of cryosperm after oncological treatments of unilateral testicular cancer. Participants/materials, setting, methods A systematic literature search was conducted in Medline, Embase and Cochrane in December 2022. For the systematic review, studies with men after all types of unilateral testicular cancer were included. For the meta-analysis, studies with unspecified treatments, < 10 patients for outcome evaluation or rare tumours were excluded. Infertility was defined as azoospermia, failure to achieve paternity or the usage of cryosperm. The quality of the individual studies was assessed using the Newcastle-Ottawa Scale. Main results and the role of chance A total of 126 studies remained following screening of the abstracts and fulltext for the subject of the study. Of these, 30 studies including 13718 men with a history of unilateral testicular cancer were eligible and analysed for qualitative synthesis. Sample sizes ranged from 17 to 4846 patients with a follow-up from 1-30 (mean 6.5) years. Histology included seminomas (43.9%), non-seminomas (49.6%) and sex cord or stromal tumors (0.01%). Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Spermiograms after treatment were analysed in 17 studies. A quantitative synthesis was performed in 23 studies. To account for heterogeneity observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The overall pooled prevalence of infertility (95% CI) in men with unilateral testicular cancer after standard oncological treatment was 14% (9-21%). Azoospermia after all types of oncological treatments appeared in 8% (6-12%) of the pooled study population. For good-prognosis patients who received standard therapy (i.e. surgery with or without retroperitoneal lymph node dissection, low- or standard dosed platin-based chemotherapy up to four cycles and / or radiotherapy), the overall prevalence of infertility was only 4% (2-10%). Limitations, reasons for caution First, the majority of the studies based on either questionnaire or register data with evident selection bias. Second, further subgroup analysis was impossible due to predominantly mixed treatment cohorts allowing only an approximation of standard therapy effects. Third, infertility might have occurred due to factors besides the oncological therapy. Wider implications of the findings Our meta-analysis includes all men with fertility outcome after testicular cancer therapy. Despite the overall low prevalence of infertility, sperm cryopreservation should still be recommended since it is unclear which therapy will follow after surgery and since there is no large longitudinal data for the various individual treatment effects. Trial registration number PROSPERO (Registry number CRD42023384057)

Long-term survival outcomes of systemic therapy in patients with isolated and mixed medullary thyroid cancer

BackgroundMedullary thyroid carcinoma (MTC) is an uncommon thyroid cancer with limited treatment options for advanced disease. A small subset exhibits mixed MTC histology with both medullary and well-differentiated components. We investigated survival outcomes with systemic therapy in isolated versus mixed MTC using a large population-based cohort. MethodsPatients diagnosed with MTC from 2000 to 2019 were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. The overall and thyroid cancer-specific survivals were compared between isolated (n = 1814) and mixed (n = 113) MTC cohorts. The impact of postoperative systemic therapy on survival was analyzed. ResultsNo significant difference in 10-year overall survival was observed between isolated (77.4 %) and mixed (75.2 %) MTC in a cohort of 1927 patients. Median overall survival was similar between isolated (136.9 months) and mixed MTC (129.0 months), p = 0.81. While systemic therapy improved 10-year survival in isolated MTC (83.2 % vs. 76.9 %, p < 0.001), no benefit was seen in mixed MTC (76.4 % vs. 74.2 %, p = 0.82). Multivariate analysis confirmed survival gains with systemic therapy for isolated (HR = 0.763, 95%CI = 0.590–0.987, p = 0.040) but not mixed MTC (HR = 0.909, 95%CI = 0.268–3.079, p = 0.88). ConclusionsIn this large population-based study, no significant survival difference was observed between isolated and mixed MTC. Systemic therapy was associated with improved survival in isolated MTC, but not in the mixed subtype. These findings suggest a differential treatment response that warrants further investigation in prospective studies and may inform histology-tailored management strategies for mixed MTC.

Retention rates and reasons for non-retention in exercise oncology trials in the post-treatment phase-a systematic review.

Retention is a key marker of trial success. Poor retention can induce bias, reduce statistical power and minimise the validity of trials. This review examined retention rates in exercise trials in cancer survivors, reasons for non-retention and retention strategies utilised. A systematic review was conducted using a predefined search strategy in EMBASE RCTs, MEDLINE OVID, CINAHL, Web of Science-Core Collection and Cochrane Central Register of Controlled Trials (CENTRAL). The search was conducted on 27/03/2023. Title and abstract screening, full text review and data extraction were completed in duplicate. Of 17,524 studies identified, 67 trials involving 6093 participants were included. The median overall retention rate immediately post-intervention was 89.85%, range (52.94-100%) and mean 87.36% (standard deviation 9.89%). Trials involving colorectal cancer survivors only had the highest median retention rate (94.61%), followed by breast (92.74%), prostate (86.00%) and haematological cancers (85.49%). Studies involving mixed cancer cohorts had the lowest retention rate (80.18%). The most common retention strategies were wait-list control groups, regular check-ins/reminders and free exercise equipment. Common reasons for non-retention were lost to follow-up, health problems, personal reasons including family/work commitments and travel burden, and disease progression. Retention rates in exercise oncology trials are approximately 90% immediately post-interventions. Our previous work highlighted variable suboptimal recruitment rates of median 38% (range 0.52-100%). Recruitment rather than retention should be prioritised for methodology research in exercise oncology. Optimising the quality of exercise oncology trials is critical to informing high quality survivorship care. PROSPERO registration number: CRD42023421359.

Recent Status of Phase I Clinical Trials for Brain Tumors: A Regulatory Science Study of Exploratory Efficacy Endpoints

BackgroundAppropriate exploratory efficacy data from Phase I trials are vital for subsequent phases. Owing to the uniqueness of brain tumors (BTs), use of different strategies to evaluate efficacy is warranted. We studied exploratory efficacy evaluation in Phase I trials involving BTs.MethodsUsing Clarivate’s Cortellis™, 42 Phase I trials of BT interventions conducted from 2020 to 2022 were analyzed for efficacy endpoints, which were set as primary endpoints (PEs) or secondary endpoints (SEs). Additionally, these metrics were compared in two subgroups: trials including only BTs (Group-A) and those including BTs among mixed solid tumors (Group-B).ResultsSelected studies included a median of 1.5 PEs (range, 1–6) and 5 SEs (range, 0–19). Efficacy endpoints were included as PEs and SEs in 2 (5%) and 31 (78%) trials, respectively. Among the latter 31 trials that included 94 efficacy endpoints, 24, 22, 20, 9, and 8 reflected overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR), respectively. ORR for BT was determined using various methods; however, the Response Evaluation Criteria in Solid Tumors (RECIST) was used less frequently in Group-A than in Group-B (p = 0.0039).ConclusionsRecent Phase I trials included efficacy endpoints as SEs, with ORR, PFS, or OS included in ~ 50% trials and DOR or DCR in ~ 25%. No established criteria exist for imaging evaluation of BTs. Phase I trials involving mixed solid tumor cohorts revealed challenges in designing methods to assess the exploratory efficacy of BTs.

Atrial fibrillation ablation during robotic mitral valve surgery: a systematic review and meta-analysis.

Atrial fibrillation (AF) is the most common arrhythmia, and is also associated with mitral valve disease. Although the benefits of robotic mitral valve surgery are well documented, literature combining robotic mitral valve surgery with AF surgery remains sparse. The aim of this systematic review and meta-analysis is to evaluate the evidence assessing the efficacy and safety of AF ablation during robotic mitral valve surgery. Five electronic databases were searched from inception to April 2023. All studies reporting the primary outcome, freedom from AF, for patients with a history of AF undergoing robotic mitral valve surgery and AF ablation were identified. Studies which included mixed cohorts, or patients who did not undergo robotic mitral valve surgery were excluded. Relevant data were extracted and a meta-analysis of proportions was conducted using a random-effects model. Five studies were included with a total of 241 patients. Cohort sizes ranged from 11 to 94 patients. The aggregate mean age was 58.5 years and patients had persistent AF (71.1%). All five studies utilised the da Vinci® Surgical System, and performed variable lesion sets. The freedom from AF was 88.1% at a weighted mean follow-up of 6.9 months. There were two mortalities (0.8%), two patients required conversion to sternotomy (1.4%) and eight required a permanent pacemaker (3.7%). AF ablation with robotic mitral valve surgery can be performed with adequate short-term efficacy and safety profile. Current evidence on AF ablation and robotic mitral valve surgery is limited to low-quality retrospective data with inherent selection bias. Further large-scale prospective data is required to verify these results.

Vaginal Stenosis After Gender-affirming Vaginoplasty: A Systematic Review

To review the literature and report the incidence of vaginal stenosis (VS) after vaginoplasty and compare the incidence rates by surgical technique and follow-up duration. We performed a systematic literature review according to PRISMA guidelines. Original research on primary vaginoplasty was included. Exclusion criteria included non-English studies, mixed cohorts without subgroup analysis, revision vaginoplasty, and papers without stenosis rates. The search was ran in Pubmed, Embase, Scopus, and Cochrane on September 9, 2022. Stenosis rates were compared with descriptive statistics using SPSS. Fifty-nine studies with a cumulative 7338 subjects were included. The overall incidence of VS was 5.83% (range 0%-34.2%). Combining VS with introital stenosis (IS) and contracture results in a cumulative incidence of 9.68%. The rate of VS in the penile inversion vaginoplasty subgroup (PIV) was 5.70%, compared to 0.20% in primary intestinal vaginoplasty. The rate of IS in the PIV group was 3.13% and 4.7% in the intestinal vaginoplasty subgroup. The overall rate of VS was 5.83%, which is lower than previously documented. This may be related to the inclusion of more recent studies and analysis limited to primary vaginoplasty. The similar rate of IS in PIV and intestinal vaginoplasty subgroups may be secondary to multiple suture lines and the need for dilation through this anastomosis. Our research demonstrates a need for a standardized definition of VS.

Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals.

Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.

Patterns of Telemedicine Use and Glycemic Outcomes of Endocrinology Care for Patients With Type 2 Diabetes

Telemedicine can increase access to endocrinology care for people with type 2 diabetes (T2D), but patterns of use and outcomes of telemedicine specialty care for adults with T2D beyond initial uptake in 2020 are not known. To evaluate patterns of telemedicine use and their association with glycemic control among adults with varying clinical complexity receiving endocrinology care for T2D. Retrospective cohort study in a single large integrated US health system. Participants were adults who had a telemedicine endocrinology visit for T2D from May to October 2020. Data were analyzed from June 2022 to October 2023. Patients were followed up through May 2022 and assigned to telemedicine-only, in-person, or mixed care (both telemedicine and in-person) cohorts according to visit modality. Multivariable regression models were used to estimate hemoglobin A1c (HbA1c) change at 12 months within each cohort and the association of factors indicating clinical complexity (insulin regimen and cardiovascular and psychological comorbidities) with HbA1c change across cohorts. Subgroup analysis was performed for patients with baseline HbA1c of 8% or higher. Of 11 498 potentially eligible patients, 3778 were included in the final cohort (81 Asian participants [2%], 300 Black participants [8%], and 3332 White participants [88%]); 1182 used telemedicine only (mean [SD] age 57.4 [12.9] years; 743 female participants [63%]), 1049 used in-person care (mean [SD] age 63.0 [12.2] years; 577 female participants [55%]), and 1547 used mixed care (mean [SD] age 60.7 [12.5] years; 881 female participants [57%]). Among telemedicine-only patients, there was no significant change in adjusted HbA1c at 12 months (-0.06%; 95% CI, -0.26% to 0.14%; P = .55) while in-person and mixed cohorts had improvements of 0.37% (95% CI, 0.15% to 0.59%; P < .001) and 0.22% (95% CI, 0.07% to 0.38%; P = .004), respectively. Patients with a baseline HbA1c of 8% or higher had a similar pattern of glycemic outcomes. For patients prescribed multiple daily injections vs no insulin, the 12-month estimated change in HbA1c was 0.25% higher (95% CI, 0.02% to 0.47%; P = .03) for telemedicine vs in-person care. Comorbidities were not associated with HbA1c change in any cohort. In this cohort study of adults with T2D receiving endocrinology care, patients using telemedicine alone had inferior glycemic outcomes compared with patients who used in-person or mixed care. Additional strategies may be needed to support adults with T2D who rely on telemedicine alone to access endocrinology care, especially for those with complex treatment or elevated HbA1c.

NIMG-85. EVALUATING THE PERFORMANCE OF A DEEP LEARNING GLIOMA SEGMENTATION MODEL USING COMBINED PRE- AND POST-TREATMENT MRI TRAINING DATA

Abstract Identification of key phenotypic regions such as necrosis, contrast enhancement, and edema on magnetic resonance imaging (MRI) is important for understanding disease evolution and treatment response in patients with glioma. Manual delineation is time intensive and not feasible for a clinical workflow. Automating phenotypic region segmentation overcomes many issues with manual segmentation, however, current glioma segmentation datasets focus on pre-treatment, diagnostic scans, where treat-ment effects and surgical cavities are not present. Thus, existing automatic segmenta-tion models are not applicable to post-treatment imaging that is used for longitudinal evaluation of care. Here, we present a comparison of three-dimensional convolutional neural networks (nnU-Net architecture) trained on large temporally defined pre-treatment, post-treatment, and mixed cohorts. We used a total of 1563 imaging timepoints from 854 patients curated from 13 different institutions as well as diverse public data sets to understand the capabilities and limitations of automatic segmenta-tion on glioma images with different phenotypic and treatment appearance. We as-sessed the performance of models using Dice coefficients on test cases from each group comparing predictions with manual segmentations generated by trained techni-cians. We demonstrate that training a combined model can be as effective as models trained on just one temporal group. The results highlight the importance of a diverse training set, that includes images from the course of disease and with effects from treatment, in the creation of a model that can accurately segment glioma MRIs at multiple treatment time points.

Association of revascularization with mortality in ischemic left ventricular dysfunction

Abstract Background Revascularization in patients with left ventricular (LV) dysfunction has been a subject of ongoing uncertainty and conflicting results. This is further complicated by factors including viability, severity of LV dysfunction, and method of revascularization using percutaneous coronary intervention (PCI) versus coronary-artery bypass grafting (CABG). The purpose of this meta-analysis is to evaluate the association of coronary revascularization with mortality in patients with ischemic LV dysfunction. Methods A literature search was conducted for studies reporting on all-cause mortality after revascularization with PCI or CABG compared to optimal medical therapy (OMT) in patients with ischemic LV dysfunction. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. Results A total of 21 studies with 6062 participants (2838 revascularized, 3224 on OMT) met inclusion criteria. Mean follow-up was 37 months (11-68 months), mean LV ejection fraction (EF) was 29%, mean age was 61, 85% of patients were male. Revascularization was significantly associated with lower all-cause mortality compared to patients on OMT (OR 0.57, 95% CI 0.46-0.71; p&amp;lt;0.01). The association was statistically significant regardless of severity of LV dysfunction or method of revascularization. Heterogeneity between subgroups was low and test for subgroup difference was not statistically significant by EF cutoff of 35% or by revascularization method (p=0.43, I2=0%; p=0.12, I2=59.7%). Subgroup analysis by viability demonstrated that revascularization was significantly associated with lower all-cause mortality compared to OMT for patients with viability and mixed cohorts with or without viability, but not patients without viability (OR 0.47, 95% CI 0.33-0.66; p&amp;lt;0.01; OR 0.57, 95% CI 0.38-0.84; p&amp;lt;0.01; OR 0.73, 95% CI 0.51-1.02; p=0.07). The effect size was larger in the subgroup with viable myocardium compared to mixed patients with viable or non-viable myocardium (Z=4.33 vs 2.79). Conclusions Revascularization in patients with ischemic LV dysfunction is associated with lower risk of all-cause mortality independent of severity of LV dysfunction or method of revascularization. Revascularization is not associated with lower risk of all-cause mortality in patients without evidence of viable myocardium.

Abstract 241: Neurologic Complications Associated With Extracorporeal Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest

Background: Neurologic complications are frequently encountered after ECPR and there is a limited understanding of the associated clinical trajectories following ECPR for in-hospital cardiac arrest (IHCA). Aim: To determine the prevalence, properties, and outcomes of radiographic neurologic complications following ECPR for IHCA. Methods: In this single-center retrospective chart review, we collected data on all adult IHCA patients who underwent ECPR from 1/1/2018 to 12/31/2019. Measured variables included demographics, clinical data, timing of diagnostic studies, and outcomes. Results: Data were analyzed from 36 adult ECPR patients, 16 (44%) of whom survived to hospital discharge. Twenty (56%) underwent head computed tomography (CT) and 9 (25%) had pathology identified, diagnosed a median of 1.8 days afterECPR. The most common complications were intracranial hemorrhage and focal ischemia (4/9 patients each). Neurologic complications were not associated with total ECMO duration (median 4 vs 5 days, p=0.57) and patients with complications trended toward poorer survival outcomes (22% vs 52% survival to discharge; p=0.25). Conclusions: Radiographic neurologic complications occurred in one quarter of IHCA ECPR patients and were associated with trends towards poorer clinical outcomes. Consistent with data in the non-ECPR literature, rates of global anoxic injury and hospital mortality were lower in this IHCA cohort than in previously published OHCA and mixed ECPR cohorts. This study is limited by its small sample size, single center design, and lack of a standardized neuroimaging protocol. Future prospective studies are needed to assess the efficacy of ECPR for IHCA.

Predicting Postoperative Injury and Military Discharge Status After Knee Surgery in the US Army.

Researchers have assessed postoperative injury or disability predictors in the military setting but typically focused on 1 type of surgical procedure at a time, used relatively small sample sizes, or investigated mixed cohorts with civilian populations. To identify the relationship between baseline variables and injury incidence or military discharge status in US Army soldiers after knee surgery. Case-control study; Level of evidence, 3. Data were obtained from a repository containing personnel, performance, and medical records for all active-duty US Army soldiers. Multivariate logistic regressions were used to estimate the effects of numerous variables on postoperative injury or on medical discharge. Variable selection and model validation were conducted using the k-fold method. A total of 7567 soldiers underwent knee surgery between 2017 and 2019. Meniscal procedures were the most common type of surgery (39%), and approximately 71% of the cohort had a postoperative injury. Significant predictors for sustaining a postoperative injury included having a previous nonknee injury (odds ratio [OR], 1.5), female sex (OR, 1.3), and Black race (OR, 1.2). Within 4 years after surgery, 17% of soldiers were discharged from the military because of knee-related disability. Significant predictors for discharge from duty included enlisted rank (OR, 2.3), recent fitness test failure (OR, 1.9), number of previous knee surgeries (OR, 1.7), and having a previous nonknee injury (OR, 1.6). After knee surgery, nearly three-fourths of the soldiers in this cohort sustained a postoperative injury and almost one-fifth of soldiers were medically discharged from the military within 4 years. This study identified variables that indicate statistically increased risk for these postoperative outcomes and highlighted potentially modifiable factors.

Familial hemiplegic migraine in pediatric patients: A genetic, clinical, and follow-up study.

The aim of this study was to describe a cohort of pediatric patients with genetically confirmed familial hemiplegic migraine (FHM). The knowledge of genotype-phenotype correlations may suggest prognostic factors associated with severe phenotypes. Hemiplegic migraine is a rare disease and data concerning the pediatric population are even more rare as they are often extrapolated from mixed cohorts. We selected patients who met International Classification of Headache Disorders, third edition criteria for FHM, who had a molecular diagnosis, and whose first attack occurred under the age of 18 years. We enrolled nine patients (seven males and two females) first referred to our three centers. Three of the nine (33%) patients had calcium voltage-gated channel subunit alpha1 A (CACNA1A) mutations, five (55%) had ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2) mutations, and one had both genetic mutations. The patients experienced at least one aura feature other than hemiplegia during the first attack. The mean (SD) duration of HM attacks in the sample was 11.3 (17.1) h; 3.8 (6.1) h in the ATP1A2 group, and 24.3 (23.5) h in the CACNA1A group. The mean (SD, range) duration of follow-up was 7.4 (2.2, 3-10) years. During the first year from the disorder's onset, only four patients had additional attacks. Over the course of follow-up, the attack frequency overall was 0.4 attacks/year without a difference between the two groups (CACNA1A and ATP1A2). The study data show that most of our patients with early-onset FHM experienced infrequent and non-severe attacks, which improved over time. Furthermore, the clinical course revealed neither the appearance of novel neurological disorders or a deterioration of basic neurological or cognitive functioning.

Survival of patients with solid tumors and sepsis admitted to intensive care in a tertiary oncology center: A retrospective analysis.

6586 Background: Sepsis is a life threatening organ dysfunction caused by a dysregulated host response to infection. Patients with cancer are at high risk of developing sepsis and requiring admission to the intensive care unit (ICU). Patients with cancer and sepsis have been found to have worse survival than non-cancer patients, with 90 day survival for cancer patients ranging from 28% to 72%. Survival differs between studies due to multiple factors including variably mixed haemato-oncology and solid tumor cohorts and varying definitions of sepsis. Our objectives were to accurately assess short, medium and long term survival of patients admitted to ICU with a solid tumor and sepsis and to identify the best predictors of 90 day survival at admission. Methods: We conducted a retrospective cohort survival analysis. We identified adults (aged 18 years and over) admitted to ICU with sepsis and a solid tumor between 1st January 2011 and 31st December 2020 at a tertiary oncology center with hospitals at two sites (London and Surrey, United Kingdom). We defined sepsis using the Sepsis-3 definition. The primary outcome was 90 day survival, but we also calculated 30 day, 180 day, 1 year and 5 year survival. Survival was calculated excluding patients lost to follow up. Univariate and multivariate analyses were undertaken to identify factors that differed between survivors and non-survivors at day 90. We used the parametric accelerated failure time model for multivariate analysis to generate time ratios (TR). Results: 625 patients were identified, with 131 patients lost to follow up by 5 years. The median age was 64 years (Interquartile Range 54-71) and 56% were male. 84.8% (530/625) survived to ICU discharge. The 30, 90 and 180 day survival rates were 72% (439/610), 59.5% (353/593) and 51.7% (300/580) respectively. 1 year survival was 38.7% (221/571) and 5 year survival 8.1% (40/494). Multivariate analysis identified the presence of localized (TR 7.85, 95% CI 4.00 -15.41) or regionalized disease (TR 4.71, 95% CI 2.74-8.08) compared to distant metastatic disease, surgery on the day of admission (TR 6.78, 95% CI 3.24-14.19), lactate (TR 0.80, 95% CI 0.74-0.87), SOFA score (TR 0.84, 95% CI 0.79-0.89), previous radiotherapy (TR 0.53, 95% CI 0.32-0.88), previous medical cancer treatment (TR 0.67, 95% CI 0.42-1.07), bacteremia (TR 2.14, 95% CI 1.25-3.64) and albumin (TR 1.06, 95% CI 1.02-1.10) as independent predictors of 90 day survival. Conclusions: This study of solid tumor patients admitted to ICU is one of the largest to date with the longest follow up period, providing up to date survival data to inform clinicians and patients. Patients with solid tumors and sepsis admitted to ICU have short and medium term survival rates comparable to non-cancer populations and therefore the presence of cancer should not prevent ICU admission. Prior oncological therapies may affect survival in patients admitted to ICU with sepsis.

Drain fluid biomarkers for the diagnosis of clinically relevant postoperative pancreatic fistula: a diagnostic accuracy systematic review and meta-analysis.

Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimized. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis. Five databases were searched for relevant and original papers published from January 2000 to December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies. Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs were determined. Potential triage tests (negative predictive value >90%) were identified for the ruling out of CR-POPF and included postoperative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300U/l) and in mixed surgical cohorts (2500U/l), POD3 drain amylase in PD patients (1000-1010U/l) and drain lipase in mixed surgery groups (180U/l). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1. The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multivariable risk-stratification models and the improvement of pancreatectomy outcomes.

Actuarial fairness and social welfare in mixed-cohort tontines

We study actuarial fairness in tontines with heterogeneous cohorts. For a given tontine, we show that both collective and individual actuarial fairness can be achieved. While it is impossible to design a tontine scheme with mixed cohorts that is optimal (utility-maximizing) for each single cohort (Milevsky and Salisbury (2016), Chen et al. (2021d)), we design a socially optimal tontine that maximizes the collective's expected utility which is characterized through a weighted sum of individual utility functions. In particular, we compare the resulting collectively optimal tontine to existing schemes in the literature, and identify similarities and differences as well as potential (dis-)advantages.

Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis

AimsClostridioides difficile infection (CDI) is a major challenge for healthcare systems. Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a risk factor for primary and recurrent CDI (rCDI). Moreover, CDI itself often worsens the clinical picture of IBD, increasing the risk of complications. Fecal microbiota transplantation (FMT) is a highly effective treatment for rCDI, but data from patients with IBD and CDI are limited and often referred to mixed cohorts. We aimed to report outcomes from a cohort of patients with UC treated with FMT for rCDI superinfection. Methods and resultsIn a retrospective, single-centre cohort study we evaluated characteristics and outcomes of patients with UC who received FMT for rCDI. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Thirty-five patients were included in the analysis. Sixteen patients were cured after single FMT, while 19 patients received repeat FMT. Overall, FMT cured rCDI in 32 patients (91%), and repeat FMT was significantly associated with sustained cure of CDI compared with single FMT (84% vs 50%, p = 0.018). Twenty-four patients (69%) experienced remission or an amelioration of UC activity. Serious adverse events were not observed. ConclusionsIn our cohort of patients with UC, FMT was highly effective in curing rCDI without severe adverse events and repeat FMT was significantly associated with CDI cure. Most patients also experienced remission or amelioration of UC activity after FMT. Our findings suggest that a sequential FMT protocol may be used routinely in patients with UC and rCDI.