Single Cohort Study Research Articles

The trend in delayed childbearing and its potential consequences on pregnancy outcomes: a single center 9-years retrospective cohort study in Hubei, China

BackgroundDue to the advancement of modern societies, the proportion of women who delay childbearing until or beyond 30 years has dramatically increased in the last three decades and has been linked with adverse maternal-neonatal outcomes.ObjectiveTo determine the trend in delayed childbearing and its negative impact on pregnancy outcomes.Material and methodsA tertiary hospital-based retrospective study was conducted in Wuhan University Renmin Hospital, Hubei Province, China, during the years 2011–2019. The joinpoint regression analysis was used to find a trend in the delayed childbearing and the multiple binary logistic regression model was used to estimate the association between maternal age and pregnancy outcomes.ResultsBetween 2011 and 2019, the trend in advanced maternal age (AMA ≥35 years) increased by 75% [AAPC 7.5% (95% CI: − 10.3, 28.9)]. Based on maternal education and occupation, trend in AMA increased by 130% [AAPC 11.8% (95% CI: 1.1, 23.7)] in women of higher education level, and 112.5% [AAPC 10.1% (95% CI: 9.4, 10.9)] in women of professional services. After adjusting for confounding factors, AMA was significantly associated with increased risk of gestational hypertension (aOR 1.5; 95% CI: 1.2, 2.1), preeclampsia (aOR 1.6; 95% CI: 1.4, 1.9), sever preeclampsia (aOR 1.7; 95% CI: 1.1, 2.6), placenta previa (aOR 1.8; 95% CI: 1.5, 2.2), gestational diabetes mellitus (aOR 2.5; 95% CI: 2.3, 2.9), preterm births (aOR 1.6; 95% CI: 1.4, 1.7), perinatal mortality (aOR 1.8; 95% CI: 1.3, 2.3), and low birth weight (aOR 1.3; 95% CI: 1.2, 1.4) compared with women aged < 30 years.ConclusionOur findings show a marked increase in delayed childbearing and its negative association with pregnancy outcomes.

PB2361: PREDIGA, EDUCATIONAL AND DIAGNOSIS PROJECT IN ACID SPHINGOMYELINASE DEFICIENCY DISEASE (ASMD) AND GAUCHER DISEASE (GD): RESULTS TO THE OBJECTIVE ACHIEVED OF 200 PATIENTS ANALYZED.

Background: Acid sphingomyelinase deficiency disease (ASMD) and Gaucher disease (GD) are lysosomal disorders caused by deficiency of lysosomal enzymes acid beta-glucosidase and acid sphingomyelinase. These enzyme deficiencies cause accumulation of glucocerebroside and sphingomyelin, respectively, mainly in macrophages, inducing deterioration of the organs in which they accumulate. Theoretical prevalence of ASMD is 0.4 per 100,000 and GD is 1 per 40,000. The absence of epidemiological studies in Spain leads us to believe that ASMD is highly underdiagnosed, and that the incidence of GD data is still to be defined. The consequences of undertreatment and the availability of effective therapies make it increasingly necessary to promote awareness and knowledge of these diseases and their diagnostic algorithms. Aims: The main objective of this study is to identify patients with idiopathic splenomegaly or splenectomy as well as to promote awareness and knowledge of ASMD and GD and their diagnosis algorithm through a national medical education program. Prevalence of ASMD and GD in patients with idiopathic splenomegaly or splenectomy will be also established. Methods: Regarding educational program, the participating centers lead clinical sessions as part of the PREDIGA education program. It was planned to impart about 100 clinical sessions within the medical education program and reach 200 patients fulfilling diagnostic criteria for ASMD and GD in the recruitment process. In addition, PREDIGA project included an epidemiological, clinical, observational, non-interventional, multicenter, retrospective and prospective, cross-sectional with a single cohort study. The study population included adults and children with idiopathic splenomegaly or splenectomy. We performed a retrospective (5 years) and prospective review (2 years) of medical records to detect sustainable patients. In a single visit, the informed consent form was signed and the patient’s clinical data were recorded. We used the usual clinical procedures to collect a blood sample for Dry Blood Spot (DBS) to perform enzymatic, genetic, and biomarkers analyses. The analysis of the samples was performed in the Archimed laboratory using ArchimedLife platform. The diagnostic algorithm for the analysis of the samples included two steps: first, enzymatic analysis was performed and if the result was positive or doubtful, genetic analysis was performed to confirm the positive result for ASMD or GD. In addition, samples which results were positive for ASMD or GD were subjected to analysis of the biomarkers Lyso-Gl1 or Lyso-SM. Results: 52 HCPs (22 Hematologists/ 18 Internal Medicine/ 12 Pediatricians) from 34 hospitals had implemented the medical education program and epidemiological searching in their health area of influence for 2 consecutive years. To date, 49 educational sessions, on-site and virtual, have been held by research team with 1000 assistants. A total of 206 patients’ blood samples have been collected to perform a DBS. Results to date have revealed the diagnosis of 2 ASMD and 4 GD patients derived from the epidemiological program. Thanks to implementation of this educational program 2 ASMD and 1 GD patients were diagnosed. Therefore, in this study the prevalence of ASMD and GD in patients with idiopathic splenomegaly or splenectomy is 0.97% and 1.9% respectively. Summary/Conclusion: The medical educational plan and the epidemiological study derived of this project have increased awareness of these conditions allowing the diagnosis of new ASMD and GD patients and better define the prevalence of these diseases in this cohort.

Presenting Patterns of Genetically Determined Developmental Encephalopathies With Epilepsy and Movement Disorders: A Single Tertiary Center Retrospective Cohort Study.

BackgroundThis paper aimed to evaluate the frequency of observation of genetically determined developmental encephalopathies with epilepsy and movement disorders in a specialistic center, the distribution of etiologies and presenting clinical hallmarks, and the mean times for the achievement of molecular genetic diagnosis.Patients and MethodsRetrospective data about clinical phenotypes, etiology, and diagnostic pathways were collected in all the genetically confirmed patients with developmental encephalopathies with epilepsy and movement disorders referred to our institution between 2010 and 2020. The cohort was divided into two groups according to the predominant movement disorder type: 1) Group A: patients with hyperkinetic movement disorders; 2) Group B: patients with hypokinetic movement disorders. Both groups were analyzed in terms of developmental, epileptic, and movement disorder phenotypes.ResultsThe cohort included 69 patients (Group A = 53; Group B = 16). The etiological spectrum was heterogeneous with a predominance of Rett and Angelman syndrome in Group A and neurodegenerative disorders in Group B. A moderate/severe intellectual disability was assessed in 58/69 patients (mean age at the first signs of developmental impairment = 1,87 ± 1,72 years). Group A included patients with an earlier onset of epileptic seizures (2,63 ± 3,15 vs. 4,45 ± 5,55 years of group B) and a predominant generalized motor semiology of seizures at the onset. Focal seizures were the main initial epileptic manifestations in Group B. Seizures were noticed earlier than movement disorders in Group A while the opposite occurred in Group B. A higher increase in molecular genetic diagnosis was obtained in the last five years. Mean diagnostic delay was longer in Group B than in Group A (12,26 ± 13,32 vs. 5.66 ± 6.41 years). Chorea as an initial movement disorder was associated with a significantly longer diagnostic delay and a higher age at etiological diagnosis.ConclusionsThis study suggested: (a) a higher frequency of genetic defects involving neurotransmission, neuronal excitability, or neural development in patients with hyperkinetic movement disorders; (b) a higher frequency of neurodegenerative courses and a longer diagnostic delay in patients with hypokinetic movement disorders.

Safe mobilisation of transverse upper gracilis flap in patients with hip replacements

The transverse upper gracilis (TUG) flap is easily harvested to recruit a fair volume of tissue from the inner upper thigh region, making it the second choice of certain authors. Hip replacement is deemed prohibitive due to positional requirements that predispose to anterior dislocation of prosthetic femoral heads. In this report, we describe a simple and safe way to raise TUG flap in patients with existing hip prostheses, detailing patient assessments, and technical variations in a limited case series. A retrospective single cohort study was conducted on patient who underwent TUG flap-based reconstruction after hip replacement. Hip joint instability was assessed clinically and with CT. Flap harvesting was performed to prevent the extra-rotation of the femoral head by the thigh flex or dissecting the pedicle keeping the thigh straight. Eleven patients were qualified for the study, and the flap raising time was superimposable to the conventional technique. Six flaps were elevated, while the thigh was kept in the flexed position without any extra-rotation, and the pedicle dissection was completed in 5 cases by keeping the thigh in the straight position. No intra- or postoperative hip dislocations resulted. All patients ambulated on mornings after surgery, returning to daily activities within 4 weeks. TUG flap is a viable alternative that is not necessarily prohibited by existing prosthetic hips. Careful patient assessment and positioning during surgery are key considerations for safe and successful procedures.

Tumor calcification is associated with better survival in metastatic colorectal cancer patients treated with bevacizumab plus chemotherapy.

Aims: The purpose was to investigate the correlation between calcification and outcome in metastatic colorectal cancer (mCRC) patients who received bevacizumab plus chemotherapy as the first-line treatment. Methods: A single retrospective cohort study was conducted with all diagnosed mCRC cases who received bevacizumab and chemotherapy as the first-line therapy. Results: Among all enrolled patients (n=159), 31 had tumor calcification. The median overall survival and progression-free survival were significantly better in patients with tumor calcification than in those without calcification. A higher objective overall response rate was also observed in the tumor calcification group. On multivariate analysis, tumor calcification was independently associated with overall survival and progression-free survival. Conclusions: Tumor calcification was independently associated with improved survival in mCRC patients treated with bevacizumab plus chemotherapy.

MpMRI-US Fusion-Guided Targeted Cryotherapy in Patients with Primary Localized Prostate Cancer: A Prospective Analysis of Oncological and Functional Outcomes.

Simple SummaryTargeted cryotherapy is an emerging treatment for prostate cancer (PCa). mpMRI is a powerful tool for image fusion techniques that deliver incremental precision in diagnostic and treatment of PCa. Fusion targeted cryotherapy (FTC) arises from the simultaneous application of both these procedures. Recurrence is a concern after any type of PCa treatment, especially after targeted treatments. In this article we investigate the recurrence rate after FTC and the role of Prostate-Specific Antigen (PSA) as a predictor of recurrences. Our research provides new evidence on the feasibility of FCT by providing new insights on patient management.Targeted therapy (TT) for prostate cancer (PCa) aims to ablate the malignant lesion with an adequate margin of safety in order to obtain similar oncological outcomes, but with less toxicity than radical treatments. The main aim of this study was to evaluate the recurrence rate (RR) in patients with primary localized PCa undergoing mpMRI/US fusion targeted cryotherapy (FTC). A secondary objective was to evaluate prostate-specific antigen (PSA) as a predictor of recurrences. We designed a prospective single-center single-cohort study. Patients with primary localized PCa, mono or multifocal lesions, PSA ≤ 15 ng/mL, and a Gleason score (GS) ≤ 4 + 3 undergoing FTC were enrolled. RR was chosen as the primary outcome. Recurrence was defined as the presence of clinically significant prostate cancer in the treated areas. PSA values measured at different times were tested as predictors of recurrence. Continuous variables were assessed with the Bayesian t-test and categorical assessments with the chix-squared test. Univariate and logistic regression assessment were used for predictions. A total of 75 cases were included in the study. Ten subjects developed a recurrence (RR: 15.2%), while fifty-six (84.8%) patients showed a recurrence-free status. A %PSA drop of 31.5% during the first 12 months after treatment predicted a recurrence with a sensitivity of 53.8% and a specificity of 79.2%. A PSA drop of 55.3% 12 months after treatment predicted a recurrence with a sensitivity of 91.7% and a specificity of 51.9%. FTC for primary localized PCa seems to be associated with a low but not negligible percentage of recurrences. Serum PSA levels may have a role indicating RR.

A single centre 20-year retrospective cohort study: Percutaneous endoscopic colostomy.

Percutaneous endoscopic colostomy (PEC) represents an important intervention in specific patients. Limited data currently exist. We present the largest recorded study of patients undergoing PEC. Retrospective analysis of consultant logbooks highlighted all patients from 1997 to 2020. Two independent reviewers assessed records. Parameters measured were age, sex, indication, number of sites, complications, mortality and survival. Three subgroups were identified: recurrent sigmoid volvulus (RSV), pseudo-obstruction and neurogenic. ANOVA, chi-squared and Fischer's exact tests were utilized; Kaplan-Meier curves estimated survival and the log-rank test was applied. A p value of <0.05 was considered statistically significant. Ninety-six PEC insertions were done on 91 patients (five reinsertions). There were 66 men (69%) and the mean age was 73.1 years (interquartile range 23). The indications were RSV n=72, pseudo-obstruction n=13, neurogenic n=11. The 30-day complication rate was overall n=27 (28%), RSV n=23, pseudo-obstruction n=4. Nine patients leaked (9.9%) (eight RSV, one pseudo-obstruction), of whom five died. 90-day mortality was 14.6% (14 patients), 18.5% (13/72) for RSV, 7.7% (1/13) for pseudo-obstruction. Overall recurrence following PEC was 10.4%. The median follow-up was 25 months (interquartile range 4.6-62.2months). At 3, 5 and 10 years survival was 46%, 34% and 26% for RSV, 70%, 55% and 15% for pseudo-obstruction and 91%, 91% and 81% for neurogenic respectively. Recurrent sigmoid volvulus and pseudo-obstruction patients undergoing PEC compared to neurogenic patients have poorer outcomes with higher complication rates and shorter life expectancy. We advocate that high volume specialist units undertake PEC. The significant associated risks of PEC require careful consideration when determining patient suitability. Utilizing risk stratification scores may help guide shared decision making between patients, relatives and clinicians.

Frequency of Chlamydia trachomatis and Neisseria gonorrhoeae in Patients with Imminent Preterm Delivery on the Island of Curaçao.

Sexually transmitted infections are one of the important risk factors for preterm delivery, which is among the important contributors to perinatal morbidity and mortality. The aim of this study was to assess the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in women with imminent preterm delivery in Curaçao, an island of the Dutch Caribbean. All women from Curaçao with either preterm premature rupture of the membranes or preterm labor, common indications of imminent preterm delivery, and presenting at the Curaçao Medical Center between 15 November 2019 and 31 December 2020, were included in this single cohort study. Data were retrospectively collected from medical records. The presence of Chlamydia trachomatis and Neisseria gonorrhoeae was assessed by Cepheid GeneXpert ® (Xpert) CT/NG assay (Sunnyvale, CA, USA). In the included cohort, the prevalence of Chlamydia trachomatis infection was 15.5% and of Neisseria gonorrhoeae infection was 2.1%. All patients infected with Neisseria gonorrhoeae were co-infected with Chlamydia trachomatis. The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients with imminent preterm delivery in Curaçao is high. It is recommended to test all patients with imminent preterm delivery for these sexually transmitted infections and possibly consider testing all women in early pregnancy on the island.

Lifestyle, demographic and Skindex measures associated with cutaneous T-cell lymphoma: a single institution cohort study.

Cutaneous T-cell lymphoma (CTCL) risk factors and associated quality of life are poorly understood. Previous studies of CTCL risk factors explored patient comorbidities and lifestyle exposures, but not in conjunction with disease stage, subtype, severity, or health-related quality of life (HRQoL). We investigated lifestyle exposures and demographic factors associated with advanced-stage disease, increased disease severity, and poorer HRQoL outcomes in this single-center cohort study. A cohort survey study was conducted at Northwestern's Multidisciplinary Cutaneous Lymphoma specialty clinic between April 2019 and June 2021. REDCap surveys were administered to 140 patients with CTCL, investigating patients' demographics, lifestyle and chemical exposures. QoL was evaluated using the Skindex survey; pain and itch with ten-point Likert scales. Modified Severity Weighted Assessment Tool (mSWAT), disease stage, and disease subtype were confirmed upon enrollment in the study by a single board-certified dermatologist specializing in CTCL. Factors were compared by t test or Fischer's exact test. Median age was 63years (range 14-92) with male-to-female ratio of 1.2:1. The most common diagnosis was CD4 + MF (n = 94, 67.1%). Common lifestyle exposures included smoking (past or current) (52.3%) and chemical exposure history (all sources [53.7%]; industrial only [33.0%]). History of chemical exposures were associated with advanced stage disease (p = 0.003) and worse QoL outcomes (p = 0.001). There were significant racial differences, respectively, in early (I-IIA) vs late (IIB-IV) stage disease (p = 0.003). Obesity, hygiene, smoking, recent sun exposure, education and atopy were not significantly associated with disease stage or severity. We provide an analysis of lifestyle and demographic factors in the context of CTCL disease severity, stage, and HRQoL. We identified race as a potential risk factor for advanced stage disease and both skin phototype and chemical exposures as a risk factor for increased disease severity as measured by mSWAT. QoL outcomes were multifactorial and significantly associated with history of chemical exposure, severe pain/itch, race, disease stage and subtype. An improved understanding of these associations may lead to better individualized care. As chemical exposure and race were found to be significant factors associated with advanced-stage disease, taking exposure histories and addressing racial disparities may improve care for CTCL patients.

LGG-23. Cardiac function in children and young adults treated with MEK inhibitors: a single institution retrospecive cohort study

INTRODUCTION: MEK inhibitors (MEKi) have shown efficacy in pediatric low-grade glioma, among other tumors, but have been associated with acute cardiac dysfunction in adults. Cardiac consequences in children are unknown. MATERIAL AND METHODS: We performed a single center retrospective cohort study evaluating cardiac function by echocardiography (echo) in children and young adults <21 years old receiving MEKi at Children’s Hospital Los Angeles between October 2013 and May 2018. Blinded assessment of left ventricular function by fractional shortening (FS) and ejection fraction (EF) was performed on all available echocardiograms obtained before, during, and following therapy, as well as after re-initiation of therapy. RESULTS: Twenty-six patients underwent MEKi therapy with echo follow-up during the study period. Twenty-four of these had complete echo data. Median follow-up was 12 months. Borderline EF (EF 53-57.9%) occurred in 12 (50%) patients; and 3 (12.5%) progressed to abnormal EF (EF <53%). Cardiac dysfunction, when it occurred, was mild (lowest documented EF was 45%, and lowest FS was 24.4%). EF abnormalities typically fluctuated during therapy, resolved off therapy, and recurred with MEKi re-initiation. No clinical or demographic differences were detected between those who maintained normal cardiac function and those who developed borderline or overt cardiac dysfunction. Symptomatic heart failure did not occur. CONCLUSION: In this cohort of children and young adults, MEKi use was associated with a relatively high incidence of borderline decrease in left ventricular function, often of uncertain clinical significance. There was no evidence of permanent cardiac dysfunction. Further evaluation in larger prospective trials is needed.

Change in exercise capacity measured by Cardio-pulmonary Exercise Testing (CPET) in Danish people with cystic fibrosis after initiation of treatment with Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor

BackgroundSince 2015, when the first cystic fibrosis transmembrane conductance regulator (CFTR) modulators were approved for people with cystic fibrosis (CF) homozygous for F508del-CFTR, studies have shown improved lung function after initiation of the treatment and patients experience improved physical capacity. The aim of this study was to investigate change in exercise capacity after initiation of Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor treatment (LUM/IVA, TEZ/IVA). MethodsWe performed a single group prospective observational cohort study with follow-up at six and 12 months. The study examined change in exercise capacity in people with CF initiating treatment with LUM/IVA and TEZ/IVA, measured by cardio-pulmonary exercise testing (CPET). Inclusion criteria were people with CF homozygous for F508del-CFTR aged 12 years or older eligible for LUM/IVA and TEZ/IVA treatment from June 2017 until June 2019. Primary outcomes were change in VO2peak and maximal workload. Secondary outcomes were change in muscle strength, muscle power and body composition in a subgroup of the study population. ResultsA total of 91 patients were included in the analysis. The mean change in VO2peak and VO2peak divided by body weight from baseline to 12-months follow-up was 145.7 (91.2;200.2) ml/min and 1.07 (95% CI 0.19;1.95) ml/min/kg, respectively. The mean change in maximal workload between baseline and 12 months was 14.2 Watt (95% CI 9.1;19.2). All improvements in exercise capacity were statistically significant. ConclusionsPatients in this study improved their exercise capacity by a statistically significant increase in VO2peak and maximal workload 12 months after initiation of treatment with LUM/IVA and TEZ/IVA.

P-70 Outcomes following FGFR inhibitor therapy in patients with cholangiocarcinoma: Multi-center single institution cohort experience

Cholangiocarcinomas (CCA) are a group of heterogeneous tumors arising from the biliary system. Significant sequencing efforts have provided further insights on the molecular mechanisms of this disease including fibroblast growth factor receptor (FGFR) alterations, which occurs in approximately 15-20% of intrahepatic cholangiocarcinomas. There is lack of data on outcomes of patients following cessation of FGFR inhibitor (FGFRi) therapy. Herein, we described the patient characteristics and treatment outcomes among patients with cholangiocarcinoma harboring FGFR alterations treated with chemotherapy, another targeted therapy or a second FGFRi following treatment with a first FGFRi from a multi-center single institution experience. We conducted a retrospective study of patients with pathologic confirmed diagnosis of cholangiocarcinoma treated at the Mayo Clinic Enterprise. The study was reviewed and approved by the institutional review board. The identified patients had FGFR alterations obtained from clinical genomic reports. The primary outcome was overall survival (OS) and progression free survival (PFS). Our group identified 88 advanced or metastatic cholangiocarcinoma patients, 28 males (31.8%) and 60 females (68.2%), harboring FGFR alterations who received FGFRi. Median progression free survival (PFS) on first FGFRi was 6.6 months for all patients (95% CI: 5.5 – 8.3). Following cessation of first FGFRi therapy 55% of patients received systemic therapy as next line: 67% chemotherapy or other targeted treatment and 33% received another FGFRi therapy. Median PFS for patients who received chemotherapy or other targeted agent was 2.1 months (95% CI: 1.6 – 5.7) and for patients who received a second FGFRi following first FGFRi therapy was 3.7 months (95% CI: 1.5 – not evaluable). 28% (N=25) of the patients received another FGFRi as any line after first FGFRi therapy and median PFS was 4.0 months. This is a large multi-center single institution cohort study assessing the outcomes among patients with cholangiocarcinoma treated with a second FGFRi or chemotherapy after initial treatment with FGFR inhibitors. This data reflects the real-world experience at a tertiary cancer center. Following FGFRi treatment, almost half of the patients are able to receive next line of therapy. As more novel agents are being introduced and the optimal sequencing of FGFRi is under investigation, detailed understanding of outcomes following treatment with an FGFRi is essential.

Early metabolic syndrome in testicular germ cell tumors : A prospective study from India.

e17010 Background: Metabolic syndrome (MS) is a known complication in patients of testicular germ cell tumors . Early metabolic syndrome is not well-defined and literature on the same is scarce. Methods: This is a single institutional prospective cohort study of patients with testicular germ cell tumors from Jan’2020 to June 2021 with a minimum follow-up of 6 months after treatment completion. Patients were evaluated for MS as per NCEP ATP (National Cholesterol Education Program Adult Treatment Plan) III criteria and partial MS was defined if any one abnormal criteria was present. Clinicopathologic and treatment characteristics were correlated with development of MS. Results: Thirty-six (25 nonseminomatous tumor and 11 seminoma) were included with median age of 29 yrs (range: 18-44). Treatment protocol was - platinum based chemotherapy [BEP (n = 7), EP(n = 18),VIP(n = 4) ]in 81% (n = 29/36), single agent carboplatin in 8% (n = 3/36), and surveillance only in 11% (n = 4/36) patients. Incidence of complete metabolic syndrome noted in 42% (n = 15) and partial metabolic syndrome in 36% (n = 13) of patients after median follow-up of 13.2 months (range-6-22). Deranged parameters detected were - high serum triglyceride (≥150 mg/dl) in 64% (n = 23/36), low serum HDL cholesterol (&lt; 40 mg/dl) in 53% (n = 19/36), high blood pressure (≥130/85 mm of Hg) in 47% (n = 17/36), high waist circumference (&gt; 110 cm) in 6% (n = 2/36) and high fasting plasma glucose (≥5.6 mmol/L) in 22% (n = 8/36) of patients. Median weight gain was 5 Kg (range: 2-14). The median time to development of metabolic syndrome was 143 days (range: 90-461). Hypogonadism (testosterone &lt; 433ng/dl.) showed positive correlation (degree of freedom = 0.3143) and C-reactive protein showed negative correlation (degree of freedom -0.3090) with MS, respectively. Conclusions: Majority of Testicular germ cell tumor patients (n = 28, 78%) had features of early MS, irrespective of treatment modalities. Patients with hypogonadism are more likely to develop early MS. Larger prospective studies are warranted to assess the incidence of early MS in patients with testicular germ cell tumors and to formulate appropriate health intervention to mitigate its significant long-term effects on mortality and morbidity.

The role of procalcitonin as a prognostic factor for acute cholangitis and infections in acute pancreatitis: a prospective cohort study from a European single center.

Infection in acute pancreatitis will worsen the disease prognosis. The aim of our study was to analyze the role of procalcitonin as a prognostic biomarker for infections and clinical severity. A prospective single-cohort observational study of patients diagnosed of acute pancreatitis (n=152) was designed. PCT determination was tested on admission (first 72h). Infections (biliary, extrapancreatic and infected pancreatic necrosis), need for antibiotics, urgent ERCP and severity scores for acute pancreatitis was assessed. ROC curves were designed and the area under the curve was calculated. Logistic regression for multivariate analysis was performed to evaluate the association between procalcitonin optimal cut-off level and major complications. PCT >0.68mg/dL had higher incidence of global infection, acute cholangitis, bacteraemia, infected pancreatic necrosis, use of antibiotics in general, and need for urgent ERCP. In the multivariate regressions analysis, PCT >0.68mg/dL at admission demonstrated to be a strong risk factor for complications in acute pancreatitis. PCT levels can be used as a reliable laboratory test to predict infections and the clinical severity of acute pancreatitis. High levels of PCT predict antibiotics prescription as well as the need for urgent ERCP in patients with concomitant clinically severe cholangitis.

Management of patients susceptible to malignant hyperthermia: A surgeon's perspective

ObjectivesMalignant hyperthermia (MH) susceptibility caries broad implications for the care of pediatric surgical patients. While precautions must often be taken for only a vague family history, two options exist to assess MH-susceptibility. We evaluate the use of MH precautions and susceptibility testing at a freestanding children's hospital. MethodsThis single institution retrospective cohort study identified patients of any age who received general anesthetics utilizing MH precautions over a five-year period. The electronic medical record was further queried for patients diagnosed with MH. The indication for MH precautions and uses of susceptibility testing are assessed. Secondary outcomes included a diagnosis of bona fide MH. ResultsA total of 125 patients received 174 anesthetics with MH precautions at a mean age of 114 months (0–363 months). Otolaryngology was the procedural service most frequently involved in the care of the cohort (n = 45; 26%). A reported personal or family history of MH (n = 102; 59%) was the most common indication for precautions, followed by muscular dystrophy (n = 29; 17%). No MH events occurred in the cohort and further review of ICD-9 and -10 diagnosis codes found no MH diagnoses. No study subjects received muscle biopsy and contracture testing and only 5 (4%) underwent genetic testing for genomic variants known to cause MH susceptibility. A case example is given to highlight the implications of a reported MH history. ConclusionOtolaryngologists should maintain a familiarity with the precautions necessary to manage patients at risk for MH and MH-like reactions. Without an accessible test to rule out susceptibility, surgeons must rely on a careful history to appropriately utilize precautions. An inappropriate label of “MH-susceptible” may result in decreased access to care and treatment delays.

Biopsychosocial Factors Associated With Return to Preinjury Sport After ACL Injury Treated Without Reconstruction: NACOX Cohort Study 12-Month Follow-up.

The limited research on prognosis after nonsurgical management of anterior cruciate ligament (ACL) injury has focused on physical factors. We aimed to assess relationships between key patient-reported outcomes, in line with a biopsychosocial approach, and returning to preinjury sport at 12 months after ACL injury treated without reconstruction. We hypothesized that biopsychosocial factors would be associated with returning to preinjury sport at 12 months after ACL injury. Prospective single cohort study. Level 2. Patients who had an ACL injury and did not have reconstruction during the first year after injury were recruited from healthcare clinics in Sweden, and followed up at 3, 6, and 12 months after injury. Return to preinjury sport at 12 months was the primary outcome. Explanatory variables were psychological readiness to return to sport, knee-related quality of life, and self-reported knee function. Using generalized estimating equations, we evaluated the relationships between the explanatory variables and the primary outcome at each timepoint. Data were analyzed for 88 participants with a median age of 27 years (15-40 years). Soccer was the most frequently reported preinjury sport (n = 22). Forty participants (46%) had returned to their preinjury sport at 12 months after ACL injury. The odds of returning to preinjury sport at 12 months increased with higher self-reported knee function at 6 months (odds ratio [OR], 1.1; 95% CI, 1.0-1.1), and the odds of being returned to the preinjury sport at 12 months doubled for every 1-point increase (1-10 scale) in psychological readiness to return to sport measured at 12 months (OR, 1.9; 95% CI, 1.2-3.2). Superior self-reported knee function at 6 months and greater psychological readiness to return to sport at 12 months were associated with returning to the preinjury sport 1 year after ACL injury treated without reconstruction. Consider highlighting the relevance of biopsychosocial factors to returning to preinjury sport after ACL injury when discussing prognosis during shared decision-making.

Utility of Thromboelastography and velocity curve derivative in diagnosing COVID-19 associated coagulopathy.

BackgroundCOVID‐19 associated coagulopathy (CAC) can either be localized or systemic hypercoagulable state with increased risk of thromboembolism. This study looked into the usefulness of Thromboelastography (TEG) and the velocity curve (V‐curve) derivative from TEG in diagnosing and differentiating different stages of CAC.Materials and MethodsA prospective single cohort study of RT‐PCR confirmed COVID‐19 patients was carried out for 2 weeks. Severe COVID‐19 patients in the adult critical care units with a TEG report were recruited for the study. Citrated kaolin TEG was performed on the day of admission before anticoagulation. TEG parameters included were R and K time, alpha angle, maximum amplitude, clotting index, lysis at 30 min. The first‐degree velocity curve of TEG is plotted as V‐curve which extrapolates thrombus generation potential. Parameters analyzed were the maximum rate of thrombus generation as well as thrombus generated (TG).ResultsThe study included 43 patients with an average age of 58.34 (±15.35). TEG as well as V‐curve of all the patients were hypercoagulable compared with age‐matched reference range. We had 79.06% of patients in hypercoagulable stage. The mortality rate was 32.56% and 30.23% developed thrombotic incidents. Patients who succumbed to death had prolonged PT, aPTT, MA, Ly30, with a reduced TG (p < .05). The presence of fibrinolysis was associated with thromboembolism (OR = 6.76, CI = 1.48–25.82). Repeat TEG was done randomly in 11 patients and revealed a persistent hypercoagulable stage with increasing fibrinolysis activity.ConclusionTEG is a useful tool in diagnosing and categorizing Coagulopathy associated with COVID‐19.

Association of volumetric-modulated arc therapy with radiation pneumonitis in thoracic esophageal cancer.

The lung volume receiving low-dose irradiation has been reported to increase in volumetric-modulated arc radiotherapy (VMAT) compared with three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal cancer, which raises concerns regarding radiation pneumonitis (RP) risk. This single institutional retrospective cohort study aimed to explore whether VMAT for thoracic esophageal cancer was associated with RP. Our study included 161 patients with thoracic esophageal cancer, of whom 142 were definitively treated with 3DCRT and 39 were treated with VMAT between 2008 and 2018. Radiotherapy details, dose–volume metrics, reported RP risk factors and RP incidence were collected. The RP risk factors were assessed via multivariate analysis. Dose–volume analysis showed that VMAT delivered more conformal dose distributions to the target volume (P < 0.001) and reduced V30 Gy of heart (57% vs 41%, P < 0.001) but increased V5 Gy (54% vs 41%, P < 0.001) and V20 Gy (20% vs 17%, P = 0.01) of lungs compared with 3DCRT. However, the 1-year incidence rates of RP did not differ between the two techniques (11.3% in 3DCRT vs 7.7% in VMAT, P = 0.53). The multivariate analysis suggested that the presence of interstitial lung disease (ILD) (P = 0.01) and V20 Gy of lungs ≥20% (P = 0.008) were associated with RP. Conclusively, VMAT increased the lung volume receiving low to middle doses irradiation, although this might not be associated with RP. Further studies are needed to investigate the effect of using VMAT for delivering conformal dose distributions on RP.

Serial (1-3)-beta-D-Glucan (BDG) monitoring shows high variability among premature neonates.

Neonatal invasive candidiasis (NIC) presents high morbi-mortality. The diagnosis of NIC is often challenging. Blood cultures have limitations and better diagnostic tools are needed. Beta-D-glucan is a diagnostic marker which could be potentially used, although still more clinical data are required.

Liver-Directed Concurrent Chemoradiotherapy versus Sorafenib in Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis.

This study aimed to investigate the efficacy of liver-directed concurrent chemoradiotherapy (LD-CCRT) compared with sorafenib in patients with liver-confined locally advanced hepatocellular carcinoma (HCC) presenting portal vein tumor thrombosis (PVTT). This single institute retrospective cohort study included patients treated with sorafenib or LD-CCRT between 2005 and 2016. Patients with extrahepatic disease and those without PVTT were excluded, leaving 28 and 448 patients in the sorafenib and LD-CCRT groups, respectively. Propensity score matching was performed to balance the differences in clinical features between the two groups. At baseline, the sorafenib group presented higher incidences of unfavorable clinical features, including type III-IV PVTT (53.6% vs. 30.6%, p = 0.048) and bilateral disease extent (64.3% vs. 31.5%, p = 0.001), than the LD-CCRT group. A total of 27 patients from the sorafenib group and 52 patients from the LD-CCRT group were matched. At a median follow-up of 73 months, the median overall survival (OS) was 4.3 and 9.8 months in the sorafenib and LD-CCRT groups, respectively (p = 0.002). Patients with PVTT type II and higher benefited more from LD-CCRT in terms of OS. The Cox proportional hazard model showed that LD-CCRT was a significant prognostic factor for OS. One patient from the sorafenib group and seven patients from the LD-CCRT group underwent curative surgical treatment. Patients who underwent surgical treatment had significantly longer OS. In conclusion, LD-CCRT showed superior survival outcomes to sorafenib in HCC patients with PVTT. LD-CCRT needs further consideration for its substantial local tumor control that can enable curative surgical treatment in selected patients.