Prospective Case-cohort Study Research Articles

Value of foetal umbilical vein standardised blood flow volume in predicting weight gain in the third trimester: a prospective case-cohort study.

This study aims to establish a prediction model of foetal umbilical vein standardised blood flow volume (sQuv) on estimated foetal weight (EFW) in the third trimester. A case-cohort study involving 200 eligible normal foetuses was conducted at the Ultrasound Department of Longquanyi District of Maternity and Child Healthcare Hospital between June 1, 2020 and December 31, 2021. Ultrasound measurements were taken at two separate intervals to assess EFW and the rate of EFW (rEFW) [first: between 28 w and 33 w6d of gestational age (GA); second: after 4-6 weeks]. Umbilical vein blood flow volume (Quv) and sQuv (normalised with EFW) were calculated only during the initial measurement. Using general linear regression, a prediction model for EFW based on GA and sQuv was developed, with the gestational week employed as a calibration scalar and validated using linear regression cross-validation. In the third trimester, EFW exhibited significant correlations with GA, abdominal circumference (AC), head circumference (HC) and Quv (all ρ > 0.6, P < 0.001). Furthermore, the rEFW showed significant correlations with Quv and sQuv (all ρ > 0.6, P < 0.001). A linear regression equation was established using a general linear regression model: rEFW = 0.32689 × sQuv. Additionally, a foetal weight prediction model (EFW = -2,554.6770 + 0.9655 × sQuv + 129.6916 × GA) was established using sQuv. The above two formulas were cross-validated by intra-group linear regression and proved to be of good efficacy. In the third trimester, EFW displayed significant correlations with GA, AC, HC and Quv. Additionally, the rEFW exhibited significant correlations with Quv and sQuv. The sQuv during the third trimester has predictive value for foetal weight, serving as an early warning indicator.

Plasma Albumin, Bilirubin, and Uric Acid and the Subsequent Risk of Cancer: A Case-Cohort Study in the Japan Public Health Center-based Prospective Study.

Several epidemiological studies have investigated the circulating levels of albumin, bilirubin, and uric acid (UA) in relation to cancer risk; however, they have provided equivocal evidence. In this prospective case-cohort study, we aimed to explore the association of plasma albumin, bilirubin, and UA levels with cancer incidence. We measured the plasma levels of albumin, bilirubin, and UA and investigated their association with cancer incidence in 3,584 cases and 4,270 randomly selected participants with a median follow-up of 15.8 years. The adjusted hazard ratios (HR) and 95% confidence intervals (CI) of total cancer for the highest (Q4) versus lowest quartile (Q1) was 0.77 (95% CI: 0.67-0.90, P for trend: <0.001) for albumin. This association was attenuated after excluding liver cancer cases with lower plasma albumin levels. Plasma bilirubin levels were positively related to liver cancer but inversely to total cancer after excluding liver cancer with adjusted HR Q4 vs. Q1 of 0.86 (95% CI: 0.74-0.99, P for trend = 0.015). Plasma UA levels were not dose-responsively associated with total cancer risk. Higher plasma bilirubin levels were associated with a decreased risk of total cancer after excluding liver cancer, which is likely attributed to the antioxidant properties of bilirubin.

Abstract 828: Associations of perfluoroalkyl substances with breast cancer incidence risk and mediation role of mitochondrial DNA copy number: A prospective case-cohort study

Abstract Background: Perfluorinated carboxylic acids (PFCAs) and perfluorinated sulfonic acids (PFSAs), notable representatives of perfluoroalkyl substances (PFASs), are synthetic persistent chemicals widely accumulated and detected in humans. Short-chain PFASs [PFCAs with carbon number &amp;lt;8 and PFSAs &amp;lt;6, e.g. perfluoroheptanoic acid (PFHpA)] are considered less bioaccumulative and increasingly used in commercial products, yet their health impacts are rarely investigated. Perfluorooctanoic acid (PFOA) has been categorized as a possible human carcinogen (group 2B) and a potential mammary toxicant. However, few population studies explored the prospective associations of PFOA and other common PFASs with breast cancer risk nor the underlying mechanisms. Methods: Hence, we conducted a case-cohort study within the DongFeng-Tongji Cohort, compromising 226 incident breast cancer cases and a random sub-cohort of 990 individuals. Plasma concentrations of four PFCAs [PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and PFHpA] and two PFSAs [perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS)], as well as peripheral blood mitochondrial DNA copy number (mtDNAcn) levels, were measured at baseline. Results: Using Barlow-weighted Cox regression, we found 35% and 20% increased incident risk of breast cancer for each 1-unit ln-transformed increase in PFOA and PFHpA, respectively [HR (95% CI) = 1.35 (1.03, 1.78) and 1.20 (1.02, 1.40)]. Quantile g-computation analysis revealed a 19% increased incident risk of breast cancer along with each simultaneous quartile increase in all ln-transformed PFCA concentrations [HR (95% CI) = 1.19 (1.01, 1.41)], driven mainly by contributions from PFOA (56%), PFNA (24%), and PFHpA (20%). Besides, mtDNAcn was positively associated with PFHpA levels [β (95% CI) =0.027 (0.005, 0.048)], but not with PFOA or PFNA (P&amp;gt;0.05). We also found significantly higher breast cancer risk in participants with the highest mtDNAcn (Q4, ≥1.52) than those with the lowest (Q1, &amp;lt;0.87) [HR (95% CI) =2.92 (1.69, 5.04)], and that mtDNAcn mediated 12.77% of PFHpA-breast cancer association [Indirect effect, HR (95% CI) =1.02 (1.00, 1.04)]. No significant mediation effect of mtDNAcn was observed in associations of PFOA and PFNA with breast cancer (P&amp;gt;0.05). Conclusions: Our work unveiled the relationship of short-chain PFHpA with increased incident risk of breast cancer for the first time and highlighted the intermediate role of mtDNAcn in this association, providing a research clue for exploring the potential mechanisms of PFAS-induced breast cancer. Moreover, co-exposure to PFASs was observed as a risk factor for breast cancer, shedding light on breast cancer prevention by regulating PFASs as a chemical class. Citation Format: Yue Feng, Huan Guo. Associations of perfluoroalkyl substances with breast cancer incidence risk and mediation role of mitochondrial DNA copy number: A prospective case-cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 828.

The interaction effects of zinc and polygenic risk score with benzo[a]pyrene exposure on lung cancer risk: A prospective case-cohort study among Chinese populations

The relationship of exposure to benzo[a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-year median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer cases. The baseline concentrations of benzo[a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI)=0.77 (0.66, 0.91) per SD increment in ln-transformed Zn]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to the highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer.

Perineural invasion in incisional biopsy is an indication for in-continuity resection in oral squamous cell carcinoma of the tongue and floor of the mouth.

The histologic finding of perineural invasion is a poor prognostic factor in oral squamous cell carcinoma patients. The aim of this study is to detect factors that influence prognosis in patients operated for oral cancer with perineural invasion in their histopathology report and to propose safer options of treatment with respect to recurrence and survival rates. We performed a prospective cohort study of all oral squamous cell carcinoma cases operated in our department from January 2018 to January 2022. Overall, 75 cases of patients operated for oral squamous cell carcinoma were included in the study. Of these cases, 14 with perineural invasion were found. We created two groups: one group of patients treated with in-continuity resection and a second group of patients treated with a discontinuous resection between the primary site and the neck. Type of operation was considered the predictor variable and recurrence, survival or death, the outcome variables. Oral cancer patients with known perineural invasion treated with in-continuity resection had a much better overall and disease-specific survival than patients treated with a discontinuous manner (p < .001). The difference in recurrence rate between these two groups of patients was found to be very significant in our study (p < .0005). It is therefore our suggestion that in oral squamous cell carcinoma of the tongue and floor of the mouth with perineural invasion detected in the incisional biopsy, an extended in-continuity resection to include the affected nerves should be performed.

Benzene exposure and risk of lung cancer in the Norwegian Offshore Petroleum Worker cohort: a prospective case-cohort study

ObjectiveThe objective of our study was to examine whether occupational exposure to benzene is associated with lung cancer among males in the Norwegian Offshore Petroleum Workers cohort.MethodsAmong 25 347 male...

A prospective cohort study of familial versus sporadic essential tremor cases: Do clinical features evolve differently across time?

BackgroundAlthough essential tremor (ET) is often divided into familial and sporadic cases, few data compare the evolution of clinical features in these groups over time. Leveraging data from a prospective, longitudinal study, we present analyses of the evolution of a broad range of cognitive, motor (i.e., tremor, tandem gait) and other features (e.g., disability) of ET. MethodsSixty-six familial and 23 sporadic ET cases completed in-home evaluations at baseline and 18, 36, and 54-month follow-ups. Assessments included detailed neuropsychological testing and videotaped neurological examinations. Analyses compared the longitudinal course of 16 clinical features in familial and sporadic cases. ResultsBaseline mean age was 75.2 ± 8.8 years and mean observation period was 4.7 ± 0.3 years. Tremor onset age was lower and childhood onset more common in familial than sporadic cases (p's = 0.02). Longitudinal analyses revealed no significant differences between clinical features displayed by familial and sporadic cases, or differences between the patterns of change in clinical features observed in these groups across time. Sporadic cases' daily activity skills declined significantly, whereas familial cases' did not, p's = 0.04 and 0.34, respectively; however, this finding was non-significant when controlling for false discovery rate. Several additional non-significant trends were noted. ConclusionFamilial and sporadic ET cases differed in onset age, and in the prevalence of childhood tremor onset. Although a number of interesting trends were observed, no significant differences in the evolution of clinical features over time in patients with and without a family history of ET were revealed.

Urine antimony and risk of cardiovascular disease – A prospective case-cohort study in Danish Non-Smokers

BackgroundLimited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. ObjectivesTo examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. MethodsBetween 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50–64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. ResultsIn the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DiscussionAmong this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.

“TB - Mindedness”-the only way to beat “the great mimicker”: A case series with atypical presentation of female genital tuberculosis

BackgroundIncidence of Tuberculosis (TB) cases in India reported in 2019 is 193 per 1 lakh population [National Tuberculosis Elimination Plan (NTEP)]. In India, annual extra pulmonary TB burden is 20–25%, of which 4% of cases are of urogenital origin (Revised National TB Control Programme, 2019; World Health Organization, 2019). The Ministry of Health and Family Welfare has made a target of eliminating tuberculosis by 2025 under the NTEP by the process of identification, notification and treatment of cases. Tuberculosis being a leading cause of infertility in developing countries, employing best clinical practices and being “TB-minded” will also save the patient of enormous anxiety and uncertainity and also decrease the time gap between clinical presentation and diagnosis to optimize fertility outcome. MethodologyA prospective cohort study of cases presenting with unusual findings and ultimately being diagnosed as genital tuberculosis was conducted in the gynaecology OPD, AIIMS, New Delhi, from November 2020 to November 2021 (1 year). Patients were investigated judiciously, diagnosis made and followed up for their response to anti tuberculosis therapy (ATT). ResultsThis data comprises of conglomerate of ten cases with unconventional exhibition of genital tuberculosis. 70% of the cases presented with pain lower abdomen not specifically related to menstrual cycle and often confused with IBD. Tubo ovarian mass (70%) mimicking as simple ovarian cyst, ovarian carcinoma or endometriosis was the most common clinical finding we came across.

Developmental Pathway Choices of Young People Presenting to a Gender Service with Gender Distress: A Prospective Follow-Up Study.

This prospective case-cohort study examines the developmental pathway choices of 79 young people (13.25-23.75 years old; 33 biological males and 46 biological females) referred to a tertiary care hospital's Department of Psychological Medicine (December 2013-November 2018, at ages 8.42-15.92 years) for diagnostic assessment for gender dysphoria (GD) and for potential gender-affirming medical interventions. All of the young people had attended a screening medical assessment (including puberty staging) by paediatricians. The Psychological Medicine assessment (individual and family) yielded a formal DSM-5 diagnosis of GD in 66 of the young people. Of the 13 not meeting DSM-5 criteria, two obtained a GD diagnosis at a later time. This yielded 68 young people (68/79; 86.1%) with formal diagnoses of GD who were potentially eligible for gender-affirming medical interventions and 11 young people (11/79; 13.9%) who were not. Follow-up took place between November 2022 and January 2023. Within the GD subgroup (n = 68) (with two lost to follow-up), six had desisted (desistance rate of 9.1%; 6/66), and 60 had persisted on a GD (transgender) pathway (persistence rate of 90.9%; 60/66). Within the cohort as a whole (with two lost to follow-up), the overall persistence rate was 77.9% (60/77), and overall desistance rate for gender-related distress was 22.1% (17/77). Ongoing mental health concerns were reported by 44/50 (88.0%), and educational/occupational outcomes varied widely. The study highlights the importance of careful screening, comprehensive biopsychosocial (including family) assessment, and holistic therapeutic support. Even in highly screened samples of children and adolescents seeking a GD diagnosis and gender-affirming medical care, outcome pathways follow a diverse range of possibilities.

Modifications to student quarantine policies in K-12 schools implementing multiple COVID-19 prevention strategies restores in-person education without increasing SARS-CoV-2 transmission risk, January-March 2021.

ObjectiveTo determine whether modified K–12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020–2021.MethodsWe conducted a prospective cohort study of COVID-19 cases and close contacts among students and staff (n = 65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. The projected number of school-based transmission events among untested close contacts was extrapolated from the percentage of events detected among tested asymptomatic close contacts and summed with the number of detected events for a projected total. An adjusted Cox regression model compared hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy.ResultsFrom January–March 2021, a projected 23 (1%) school-based transmission events occurred among 1,636 school close contacts. There was no difference in the adjusted hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy (hazard ratio = 1.00; 95% confidence interval: 0.97–1.03).DiscussionSchool-based SARS-CoV-2 transmission was rare in 103 K–12 schools implementing multiple COVID-19 prevention strategies. Modified student quarantine policies were not associated with increased school incidence of COVID-19. Modifications to student quarantine policies may be a useful strategy for K–12 schools to safely reduce disruptions to in-person education during times of increased COVID-19 community incidence.

Associations of mitochondrial DNA copy number with incident risks of gastrointestinal cancers: A prospective case-cohort study.

Epidemiological investigations implied that mitochondrial DNA copy number (mtDNAcn) variations could trigger predisposition to multiple cancers, but evidence regarding gastrointestinal cancers (GICs) was still uncertain. We conducted a case-cohort study within the prospective Dongfeng-Tongji cohort, including incident cases of colorectal cancer (CRC, n = 278), gastric cancer (GC, n = 138), and esophageal cancer (EC, n = 72) as well as a random subcohort (n = 1173), who were followed up from baseline to the end of 2018. We determined baseline blood mtDNAcn and associations of mtDNAcn with the GICs risks were estimated by using weighted Cox proportional hazards models. Significant U-shaped associations were observed between mtDNAcn and GICs risks. Compared to subjects within the second quartile (Q2) mtDNAcn subgroup, those within the 1st (Q1), 3rd (Q3), and 4th (Q4) quartile subgroups showed increased risks of CRC (hazard ratio [HR] [95% confidence interval, CI] = 2.27 [1.47-3.52], 1.65 [1.04-2.62], and 2.81 [1.85-4.28], respectively) and total GICs (HR [95%CI] = 1.84 [1.30-2.60], 1.47 [1.03-2.10], and 2.51 [1.82-3.47], respectively], and those within Q4 subgroup presented elevated GC and EC risks (HR [95% CI] = 2.16 [1.31-3.54] and 2.38 [1.13-5.02], respectively). Similar associations of mtDNAcn with CRC and total GICs risks remained in stratified analyzes by age, gender, smoking, and drinking status. This prospective case-cohort study showed U-shaped associations between mtDNAcn and GICs risks, but further research works are needed to uncover underlying biological mechanisms.

The value of multiparameter combinations for predicting difficult airways by ultrasound

BackgroundBased on the upper airway anatomy and joint function parameters examined by ultrasound, a multiparameter ultrasound model for difficult airway assessment (ultrasound model) was established, and we evaluated its ability to predict difficult airways.MethodsA prospective case-cohort study of difficult airway prediction in adult patients undergoing elective surgery with endotracheal intubation under general anesthesia, and ultrasound phantom examination for difficult airway assessment before anesthesia, including hyomental distance, tongue thickness, mandibular condylar mobility, mouth opening, thyromental distance, and modified Mallampati tests, was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of the ultrasound model and conventional airway assessment methods in predicting difficult airways.ResultsWe successfully enrolled 1000 patients, including 51 with difficult laryngoscopy (DL) and 26 with difficult tracheal intubation (DTI). The area under the ROC curve (AUC) for the ultrasound model to predict DL was 0.84 (95% confidence interval [CI]: 0.82–0.87), and the sensitivity and specificity were 0.75 (95% CI: 0.60–0.86) and 0.82 (95% CI: 0.79–0.84), respectively. The AUC for predicting DTI was 0.89 (95% CI: 0.87–0.91), and the sensitivity and specificity were 0.85 (95% CI: 0.65–0.96) and 0.81 (95% CI: 0.78–0.83), respectively. Compared with mouth opening, thyromental distance, and modified Mallampati tests, the ultrasound model predicted a greater AUC for DL (P < 0.05). Compared with mouth opening and modified Mallampati tests, the ultrasound model predicted a greater AUC for DTI (P < 0.05).ConclusionsThe ultrasound model has good predictive performance for difficult airways.Trial registrationThis study is registered on chictr.org.cn (ChiCTR-ROC-17013258); principal investigator: Jianling Xu; registration date: 06/11/2017).

Measurement of Saccade Parameters in Relation to Adaptation to Homonymous Hemianopia.

Purpose:To report saccade parameters in participants during adaptation to post-stroke homonymous hemianopia.Methods:In a prospective observational case cohort study, adult stroke survivors with new onset homonymous hemianopia were recruited. Using quantitative measurement, saccade parameters were measured and compared between the hemianopic and non-hemianopic sides. Two participants with longitudinal measurements were compared with age-matched controls.Results:Of 144 clinical study participants, quantitative saccade measurements were only possible in 14 due to an inability to visualise targets on the hemianopic side in the majority. In 9 of the 14 participants, at four weeks post-stroke, mean (±SD) saccade latency was significantly longer to the hemianopic (328.4 ± 105.9 ms) compared to the non-hemianopic side (234.7 ± SD53.6 ms; t = 4.2, df = 8, p = 0.003). The number of correct saccadic responses out of 50 was significantly lower to the hemianopic side (36.6 ± SD14.1) in comparison to the non-hemianopic side (44.4 ± SD7.5; t = –3.1, df = 8, p = 0.014). In two participants studied over an eight-week time period, saccadic differences to the hemianopic side persisted despite apparent recovery of visual field.Conclusion:As participants with residual visual field loss were unable to perform quantitative assessments, the widespread use of this approach in this setting is limited. However, in those whom measurements were possible, there were statistically significant differences in saccade parameters between hemianopic and non-hemianopic sides that persisted post-visual recovery. Exploration of saccades in relation to adaptation to hemianopia and response to saccadic scanning/search training requires further examination.

Return-to-Sport Criteria After Anterior Cruciate Ligament Reconstruction Fail to Identify the Risk of Second Anterior Cruciate Ligament Injury.

The incidence of second anterior cruciate ligament (ACL) injury after ACL reconstruction (ACLR) is high in young, active populations. Failure to successfully meet return-to-sport (RTS) criteria may identify adult athletes at risk of future injury; however, these studies have yet to assess skeletally mature adolescent athletes. To determine if failure to meet RTS criteria would identify adolescent and young adult athletes at risk for future ACL injury after ACLR and RTS. The tested hypothesis was that the risk of a second ACL injury after RTS would be lower in participants who met all RTS criteria compared with those who failed to meet all criteria before RTS. Prospective case-cohort (prognosis) study. Laboratory. A total of 159 individuals (age = 17.2 ± 2.6 years, males = 47, females = 112). Participants completed an RTS assessment (quadriceps strength, functional hop tests) and the International Knee Documentation Committee patient survey (0 to 100 scale) after ACLR and were then tracked for occurrence of a second ACL tear. Athletes were classified into groups that passed all 6 RTS tests at a criterion level of 90% (or 90 of 100) limb symmetry and were compared with those who failed to meet all criteria. Crude odds ratios and 95% CIs were calculated to determine if passing all 6 RTS measures resulted in a reduced risk of second ACL injury in the first 24 months after RTS. Thirty-five (22%) of the participants sustained a second ACL injury. At the time of RTS, 26% achieved ≥90 on all tests, and the remaining athletes scored less than 90 on at least 1 of the 6 assessments. The second ACL injury incidence did not differ between those who passed all RTS criteria (28.6%) and those who failed at least 1 criterion (19.7%, P = .23). Subgroup analysis by graft type also indicated no differences between groups (P > .05). Current RTS criteria at a 90% threshold did not identify active skeletally mature adolescent and young adult athletes at high risk for second ACL injury.

Dynamic change in cortisol levels associated with severity, progression, and survival of patients with traumatic brain injury

BackgroundCortisol levels are elevated in severe traumatic brain injury (TBI) and gradually decrease during patient recovery. Thus, dynamic changes in cortisol levels may serve as a prognostic biomarker of TBI. AimThis study aimed to examine the relationship between serum cortisol levels and outcomes in TBI patients. MethodsIn this prospective case-cohort study, 238 patients with TBI were enrolled. Demographic, clinical, and radiological data were recorded within the first 24 h of hospitalization. Serum cortisol levels were measured using chemiluminescence assay (Immunoassay i1000). The association between cortisol levels and outcome (Glasgow Outcome Scale score) was evaluated at discharge from the hospital and after six months of follow-up. ResultsThe mean age of the patients was 35.03 ± 17.68 years and the male: female ratio was 4.3:1. At the time of admission(day-1), cortisol levels in the TBI patients were significantly higher than those on day-7 (9.81 ± 4.20 µg/dl versus 23.41 ± 11.83 µg/dl; p<0.001). There was a significant relationship between cortisol levels and Glasgow Coma Scale (GCS) (p = 0.018). Moderate head injury (GCS;9–12) was observed in 108(45.4 %) patients and 130(54.6 %) patients with severe head injury (GCS;3–8) at presentation. CGS was significantly associated with the survival of patients with TBI; alive(n = 143) vs. dead (n = 77); p < 0.001. At 6 months follow-up of patients (n = 184), the findings revealed that the Glasgow Outcome Scale (GOS) and GCS score were significantly associated(p = 0.018). One-way ANOVA showed a significant difference in cortisol levels on day-1, day-7 and six months of sampling (p < 0.0001). Based on the GOS E score, the cortisol levels in the unfavorable and favorable groups significantly differed from those in the GOSE groups (p = 0.05). Similarly, cortisol levels were significantly associated with survival in patients with TBI (p = 0.04). With increasing cortisol levels, the GOSE score was poor and at > 50 µg/dl, no patient has survived. ConclusionsDay 1 and 7 cortisol, correlated with the outcomes at 6 months, had predictive value post-TBI.

Inter-hospital trends of post-resuscitation interventions and outcomes of out-of-hospital cardiac arrest in Singapore

Hospital-based resuscitation interventions, such as therapeutic temperature management (TTM), emergency percutaneous coronary intervention (PCI) and extracorporeal membrane oxygenation (ECMO) can improve outcomes in out-of-hospital cardiac arrest (OHCA). We investigated post-resuscitation interventions and hospital characteristics on OHCA outcomes across public hospitals in Singapore over a 9-year period. This was a prospective cohort study of all OHCA cases that presented to 6 hospitals in Singapore from 2010 to 2018. Data were extracted from the Pan-Asian Resuscitation Outcomes Study Clinical Research Network (PAROS CRN) registry. We excluded patients younger than 18 years or were dead on arrival at the emergency department. The outcomes were 30-day survival post-arrest, survival to admission, and neurological outcome. The study analysed 17,735 cases. There was an increasing rate of provision of TTM, emergency PCI and ECMO (P<0.001) in hospitals, and a positive trend of survival outcomes (P<0.001). Relative to hospital F, hospitals B and C had lower provision rates of TTM (≤5.2%). ECMO rate was consistently <1% in all hospitals except hospital F. Hospitals A, B, C, E had <6.5% rates of provision of emergency PCI. Relative to hospital F, OHCA cases from hospitals A, B and C had lower odds of 30-day survival (adjusted odds ratio [aOR]<1; P<0.05 for hospitals A-C) and lower odds of good neurological outcomes (aOR<1; P<0.05 for hospitals A-C). OHCA cases from academic hospitals had higher odds ratio (OR) of 30-day survival (OR 1.3, 95% CI 1.1-1.5) than cases from hospitals without an academic status. Post-resuscitation interventions for OHCA increased across all hospitals in Singapore from 2010 to 2018, correlating with survival rates. The academic status of hospitals was associated with improved survival.

The robotic-assisted extended "Sistrunk" approach for tumors of the upper aerodigestive tract with limited transoral access: First description of oncological and functional outcomes.

We report on the first clinical experience with the robotic‐assisted extended “Sistrunk” approach (RESA) for access to constrained spaces of the upper aerodigestive tract. This prospective case cohort study include six patients that underwent RESA if transoral exposure could not be achieved. Three patients received previous radiation. Patients were postoperatively followed until week 16 for perioperative complications, surgical margins, and functional outcomes. In all patients RESA allowed adequate exposure and resection with negative margins. Three patients who underwent salvage surgery experienced a minor or intermediate grade postoperative bleeding. No patient developed a pharyngocutaneous fistula. Three patients recovered their swallowing to their preoperative status and the remaining three experienced an improvement. All patients experienced complete recovery of their voice. RESA has the potential to provide a new organ preservation approach for head and neck cancer (HNC) not amenable to transoral exposure and thus warrants further prospective clinical studies.

Male-origin microchimerism and endometrial cancer: A prospective case-cohort study

BackgroundMany women carry male cells of presumed fetal origin–so-called male-origin microchimerism (MOM)–in their circulation and tissues. Studies have found reduced risks of hormone dependent cancers, including breast and ovarian cancer, among MOM-positive women. The aim of this study was to investigate the association between MOM and endometrial cancer. MethodsWe designed a prospective case-cohort study including 76 cases and 505 controls from the Diet, Cancer and Health cohort aged 50–64 years and cancer-free at enrolment in 1993–1997. We analyzed blood samples for the presence of Y-chromosome (DYS14). We examined the association between MOM and endometrial cancer in weighted Cox regression models. As a negative control outcome, we studied the association between MOM and injuries to test for spurious associations. ResultsWe detected MOM in 65.9% controls and 54.0% cases. While we observed no overall association between MOM and endometrial cancer (HR=0.73, 95% CI: 0.47–1.15), we found a borderline significantly reduced rate of Type 1 endometrial cancer (HR=0.66, 95% CI: 0.39–1.00), but not other types of endometrial cancers (HR=1.00, 95% CI: 0.35–2.90). The reduced rate was not modified by hormonal exposure (P = 0.79). We found no association between MOM and risk of injuries (HR=0.96, 95% CI: 95% CI: 0.78–1.21). ConclusionsOur study suggests that MOM is inversely associated with Type 1 endometrial cancer, without evidence of an interaction with hormonal exposure. We encourage future research to confirm our findings.

Predictive scoring system for risk of complications in pediatric dengue infection

Background: Dengue infection has been a worrisome cause of mortality and morbidity in children. Though numerous scoring systems have been developed, they are in the adult population or are too complicated for use in children. Pediatric dengue infection has a wide spectrum from a mild illness to severe complications and an unpredictable course. Hence the need for a predictive scoring system where the possibility of complications can be identified which can contribute to reduction in mortality and morbidity of dengue by prompt referrals and anticipatory management. Methods: Prospective case cohort study of children with confirmed dengue fever. Results: 303 children were included and divided into two groups – the dengue fever group and the complicated dengue group based on the WHO clinical classification. The clinical and laboratory parameters were analysed individually, cut offs identified by ROC curves and compared for significance between the two groups. The parameters that emerged were hypotension, PCV ≥ 42%, platelet count ≤ 75000 cells/cumm, WBC ≥ 7000 cells/cumm, and ALT ≥ 70U/L. Using the adjusted odd’s Ratio, and coefficient, individual predictive scores were tabulated ranging from 0 to 3, with a total score of 0 to 7. A cut-off score of 2 was then identified based upon the sensitivity (84.13%) and specificity (72.50%) as the ideal score to predict complicated dengue. Internal validation of the score was done where the area under the curve for predicting complicated dengue was 0.86 (95% CI 0.8-0.92) with a P value of <0.001. Conclusion: Our dengue predictive scoring system has been developed using five indicators, with a score of two and above, out of seven, suggesting increased risk of developing complications. This has been validated internally and can be used to predict complicated dengue among children.