Genetic variants associated with post-traumatic stress symptoms in patients with gynecologic cancer.

OBJECTIVE: Patients with cancer experience symptoms of post-traumatic stress disorder (PTSD) more commonly than the general population. The objective of this study was to identify single nucleotide polymorphisms (SNPs) associated with increased risk of post-traumatic stress disorder (PTSD) in patients with gynecologic cancer. METHODS: A prospective cohort study recruited 181 gynecologic cancer survivors receiving care at the University of Minnesota between 2017 and 2020 who completed PTSD DSM-V surveys to self-report their symptoms of PTSD and provided saliva samples. DNA samples were genotyped for 11 SNPs in 9 genes involved in dopaminergic, serotonergic, and opioidergic systems previously associated with risk of PTSD in populations without cancer. RESULTS: Most participants had either ovarian (42.5%) or endometrial (46.4%) cancer; fewer had cervical (7.7%) or vaginal/vulvar (3.3%) cancer. Two SNPS were identified as statistically significantly associated with higher PTSD scores: rs622337 in HTR2A and rs510769 in OPRM1. CONCLUSIONS: Genetic variation likely plays a role in development of PTSD. HTR2A is involved in the serotonin pathway, and OPRM1 is involved in the opioid receptor pathway. This information can be used by oncologic providers to identify patients at greater risk of developing PTSD and may facilitate referral to appropriate consultants and resources early in their treatment.

A Retrospective Study on the Effects of Kinesiology Taping on Edema of the Lower Limb in 14 Patients Following Intramedullary Nailing for Femoral Shaft Fracture.

BACKGROUND Kinesiology tape indications of use include pain mitigation, neurosensory input, and promotion of circulation. Current evidence suggests that residual functional limitations following intramedullary nailing of the femoral shaft may be due to soft tissue injury and compromise. This retrospective study from a single center aimed to compare the effects of kinesiology taping on edema of the lower limb in 14 patients following intramedullary nailing for femoral shaft fracture. MATERIAL AND METHODS The randomized control trial design consisting of 2 groups totaling 14 patients. The intervention group (n=7) received standard therapy and kinesiology tape decompression/fan application. The control group (n=7) received standard therapy with no kinesiology tape. Outcome measures included limb girth tape measurements, Visual Analog Scale (VAS) for pain, involved knee ROM goniometry, and Timed Up and Go (TUG). RESULTS Results of this study showed there was a decrease in limb volume in the control group and an increase in limb volume in the intervention group. Both groups had improvements in TUG scores. The only statistically significant finding was among the control group, which had a decrease of 1.6 in mean VAS score before and after IM nailing (P=0.010). CONCLUSIONS In this study from a single center, kinesiology tape in patients with intramedullary nailing for femoral shaft fracture did not significantly reduce the volume of the lower limb, reduce pain, or improve postoperative mobility. The only significant improvement from the use of kinesiology tape was improved active knee extension due to improvement in quadriceps force.

A Novel Technique to Minimize Contamination for Cervical Cancer Surgery Patients.

The Laparoscopic Approach to Cervical Cancer (LACC) trial changed the surgical management of cervical cancer worldwide. It was a multinational phase III clinical trial that reported lower survival and higher rate of abdominopelvic recurrences in minimally invasive surgery (MIS) than those of open surgery after hysterectomy. It is possible that tumor exposure to the peritoneal cavity in the MIS arm may account for these differences. We propose a novel technique to minimize peritoneal contamination of malignant cells present at the cervical os by placing a vaginal cerclage abdominally to create a seal at the apex of the vagina during MIS radical hysterectomy. The 2 patients in this work remain healthy and disease-free more than 18 months after surgery using this novel technique. We intend this work to serve as a platform both for offering a safe alternative to the open approach supported by the LACC trial and, most importantly, for promoting discussion of the results of the LACC trial and further research on surgical techniques in the treatment of cervical cancer. MIS has repeatedly been shown to have lower rates of infection, fewer complications, and shorter hospital stays while providing oncologic care that is noninferior to open approach.

Angiosarcoma of the ovary treated with polyadenosine ribose polymerase Inhibition, a case report and review of the literature.

•Primary angiosarcoma of the ovary historically has no standard treatment due to its rarity, and outcomes have been variable.•Olaparib may represent a viable treatment option for primary angiosarcoma of the ovary with a somatic BRCA mutation.•Next-generation sequencing may play an important component in treatment of very rare cancers to guide new or uncommon therapies.

Case Report: Treatment of primary pulmonary choriocarcinoma with lung lobectomy and adjuvant chemotherapy.

•Persistently elevated ß-hCG without identification of pregnancy or tumor in the gynecologic organs merits evaluation outside of the reproductive organs.•Non-metastatic primary pulmonary choriocarcinoma may be treated with curative intent with primary surgical resection and adjuvant chemotherapy.

Analytical validation of a novel multi-target blood-based test to detect hepatocellular carcinoma.

INTRODUCTION: Surveillance is essential to diagnose and more effectively treat hepatocellular carcinoma (HCC) in at-risk patients. However, the performance of currently recommended surveillance strategies is suboptimal, particularly for early-stage detection, and patient adherence remains low. Here, we establish the analytical performance of a novel liquid biopsy test to evaluate the presence of HCC. METHODS: The multi-target HCC blood test (mt-HBT) integrates results from three DNA methylation markers (HOXA1, TSPYL5, and B3GALT6), the protein biomarker α-fetoprotein (AFP), and patient sex. The methylation markers are quantified from cell-free DNA extracted from plasma, and AFP is measured from serum. We conducted analytical validation studies on the mt-HBT, including analytical sensitivity, linearity, cross-contamination, interference, analytical accuracy, and precision. RESULTS: The mt-HBT performance met all pre-specified analytical performance criteria. The test demonstrated high reproducibility, with ≥97% concordance relative to the expected results for six categories of surrogate samples across the test's dynamic range. Of 17 candidate interfering substances, none caused significant interference to biomarker quantitation, and no occurrences of sample-to-sample cross-contamination were observed. CONCLUSION: These data demonstrate that the mt-HBT can produce consistent, reliable results for patients in the intended-use population, for whom surveillance is recommended.

Effects of protein supplementation in chronic hemodialysis and peritoneal dialysis patients.

OBJECTIVE: We evaluated the impact of oral protein supplementation given during hemodialysis and peritoneal dialysis on nutritional status, number of hospitalizations, and length of stay. DESIGN: We used a randomized crossover design in which serum albumin, normalized protein catabolic rate (nPCR), total hospitalizations, and length of stay were compared in patients who received protein supplements with those who did not. The study was conducted for 1 year (November 2005 to October 2006). SETTING: This study was conducted at an outpatient dialysis facility. SUBJECTS: Forty-nine patients were treated with hemodialysis or peritoneal dialysis for at least 3 months. RESULTS: The nPCR significantly increased by month 4 of treatment from a baseline of 1.05 to 1.16 (P = .007). The control group had a significant decline in nPCR during the first 6 months, from 1.11 to 0.98 (P = .038). Improvement was evident in albumin by month 3, from 3.49 to 3.52 (P = .035), but this was not sustained. In the second 6 months, the control group had a significant drop, from 3.35 to 3.19 (P = .014), and the difference between the protein-supplementation and control groups was significant during the second 6 months (P = .037). The nPCR also dropped significantly (P = .024) for the control group in the second 6 months. When protein supplementation ended, weight dropped significantly for those with a body mass index of <20. Trends toward a reduction in hospitalization admissions and hospital days were seen in both crossover treatment groups. CONCLUSIONS: In-center supplementation of protein generally improves serum markers of nutrition overall, and when it is discontinued, these markers decline. Larger studies are needed to confirm the trends that we observed regarding nutritional markers and reductions in hospitalizations and hospitalization days.

A blood-based gene expression test for obstructive coronary artery disease tested in symptomatic nondiabetic patients referred for myocardial perfusion imaging the COMPASS study.

BACKGROUND- Obstructive coronary artery disease diagnosis in symptomatic patients often involves noninvasive testing before invasive coronary angiography. A blood-based gene expression score (GES) was previously validated in nondiabetic patients referred for invasive coronary angiography but not in symptomatic patients referred for myocardial perfusion imaging (MPI). METHODS AND RESULTS- This prospective, multicenter study obtained peripheral blood samples for GES before MPI in 537 consecutive patients. Patients with abnormal MPI usually underwent invasive coronary angiography; all others had research coronary computed tomographic angiography, with core laboratories defining coronary anatomy. A total of 431 patients completed GES, coronary imaging (invasive coronary angiography or computed tomographic angiography), and MPI. Mean age was 56±10 years (48% women). The prespecified primary end point was GES receiver-operating characteristics analysis to discriminate ≥50% stenosis (15% prevalence by core laboratory analysis). Area under the receiver-operating characteristics curve for GES was 0.79 (95% confidence interval, 0.73-0.84; P<0.001), with sensitivity, specificity, and negative predictive value of 89%, 52%, and 96%, respectively, at a prespecified threshold of ≤15 with 46% of patients below this score. The GES outperformed clinical factors by receiver-operating characteristics and reclassification analysis and showed significant correlation with maximum percent stenosis. Six-month follow-up on 97% of patients showed that 27 of 28 patients with adverse cardiovascular events or revascularization had GES >15. Site and core-laboratory MPI had areas under the curve of 0.59 and 0.63, respectively, significantly less than GES. CONCLUSIONS- GES has high sensitivity and negative predictive value for obstructive coronary artery disease. In this population clinically referred for MPI, the GES outperformed clinical factors and MPI. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01117506.

Identification of factors contributing to variability in a blood-based gene expression test.

BACKGROUND: Corus CAD is a clinically validated test based on age, sex, and expression levels of 23 genes in whole blood that provides a score (1-40 points) proportional to the likelihood of obstructive coronary disease. Clinical laboratory process variability was examined using whole blood controls across a 24 month period: Intra-batch variability was assessed using sample replicates; inter-batch variability examined as a function of laboratory personnel, equipment, and reagent lots. METHODS/RESULTS: To assess intra-batch variability, five batches of 132 whole blood controls were processed; inter-batch variability was estimated using 895 whole blood control samples. ANOVA was used to examine inter-batch variability at 4 process steps: RNA extraction, cDNA synthesis, cDNA addition to assay plates, and qRT-PCR. Operator, machine, and reagent lots were assessed as variables for all stages if possible, for a total of 11 variables. Intra- and inter-batch variations were estimated to be 0.092 and 0.059 Cp units respectively (SD); total laboratory variation was estimated to be 0.11 Cp units (SD). In a regression model including all 11 laboratory variables, assay plate lot and cDNA kit lot contributed the most to variability (p = 0.045; 0.009 respectively). Overall, reagent lots for RNA extraction, cDNA synthesis, and qRT-PCR contributed the most to inter-batch variance (52.3%), followed by operators and machines (18.9% and 9.2% respectively), leaving 19.6% of the variance unexplained. CONCLUSION: Intra-batch variability inherent to the PCR process contributed the most to the overall variability in the study while reagent lot showed the largest contribution to inter-batch variability.