Molecular Markers in Maternal Blood Exosomes Allow Early Detection of Fetal Alcohol Spectrum Disorders.

Prenatal alcohol exposure can cause developmental abnormalities (fetal alcohol spectrum disorders; FASD), including small eyes, face and brain, and neurobehavioral deficits. These cannot be detected early in pregnancy with available imaging techniques. Early diagnosis could facilitate development of therapeutic interventions. Banked human fetal brains and eyes at 9−22 weeks' gestation were paired with maternal blood samples, analyzed for morphometry, protein, and RNA expression, and apoptotic signaling. Alcohol (EtOH)-exposed (maternal self-report) fetuses were compared with unexposed controls matched for fetal age, sex, and maternal race. Fetal brain-derived exosomes (FB-E) were isolated from maternal blood and analyzed for protein, RNA, and apoptotic markers. EtOH use by mothers, assessed by self-report, was associated with reduced fetal eye diameter, brain size, and markers of synaptogenesis. Brain caspase-3 activity was increased. The reduction in eye and brain sizes were highly correlated with amount of EtOH intake and caspase-3 activity. Levels of several biomarkers in FB-E, most strikingly myelin basic protein (MBP; r > 0.9), correlated highly with morphological abnormalities. Reduction in FB-E MBP levels was highly correlated with EtOH exposure (p < 1.0 × 10−10). Although the morphological features of FAS appear long before they can be detected by live imaging, FB-E in the mother's blood may contain markers, particularly MBP, that predict FASD.

Port-Site Metastasis in Gynecological Malignancies.

BACKGROUND: Minimally invasive oncologic surgery has become the standard of care in many gynecologic cancers. While laparoscopic surgery provides many benefits to patients, such as faster recovery, there are unique challenges associated with minimally invasive techniques. Port-site metastasis is a rare complication after laparoscopic oncologic surgery in management of gynecologic malignancies. METHODS: We present the case of a 44-year-old female with isolated port-site recurrence following laparoscopic radical hysterectomy with node-negative, clinical stage IB1 cervical adenocarcinoma. In addition, we provide an updated review of the literature on management and oncologic outcomes of port-site metastasis. CONCLUSION: Port-site metastasis prevention necessitates a better understanding of underlying risk factors and pathophysiology in order to optimize outcomes. Future studies are needed on risk-reducing strategies and standardization of management for port-site metastasis.

Endometriosis Pain Management: a Review.

PURPOSE OF REVIEW: The purpose of this review is to summarize the up-to-date pain management options and recommendations for the challenging disease, endometriosis. RECENT FINDINGS: The mainstays of endometriosis advances of both surgical and medical management continue to evolve. Experimental pharmaceuticals include Gestirone, and aromatase inhibitors have shown promise but are still under scrutiny. Surgical techniques include laparoscopic uterosacral nerve ablation/resection and presacral neurectomy. No studies have directly compared medical versus surgical management, and as such, no one treatment modality can be recommend as superior to the other. Patients may initially be given a medical diagnosis and treated with nonsteroidal anti-inflammatory drugs, neurolepitcs, OCP, GNRH agonists/antagonists, and Danazol. Assessing the success of these regimens has proved difficult. Surgical management relies on various methods including excision/ablation of the lesions, nerve ablation, neurectomy, hysterectomy, and oophorectomy.

Robotic Tumor Debulking off External Iliac Vessels for the Management of Recurrent Ovarian Cancer.

OBJECTIVE: To show a surgical video in which an isolated mass was resected off the external iliac vessels for the management of recurrent ovarian cancer. DESIGN: Case report. SETTING: Tertiary referral center in New Haven, Connecticut. INTERVENTIONS: This is a step-by-step demonstration of a robotic tumor debulking in a patient with isolated recurrence of epithelial ovarian cancer [1-3]. The patient is a 70-year-old woman with Lynch syndrome who received a diagnosis for stage IIC high-grade serous ovarian adenocarcinoma and underwent complete debulking in 1996. She had most recently been on pembrolizumab for microsatellite instability-high tumor until February 2019, when she received a diagnosis for isolated hypermetabolic mass in close proximity to the external iliac vessels and right iliac fossa. The patient was placed in dorsal low lithotomy Trendelenburg position, and 15° leftward tilt of the table was obtained to expose the right pelvic sidewall and iliac fossa. To optimally target the surgical field of interest, all robotic trocars were placed in a straight line starting from 5 cm above symphysis pubis on the left side to left subcostal line between the midline vertical and the left midclavicular lines, as per the manufacturer's port placement guidelines (Fig. 1). CONCLUSION: Robotic resection of the tumor nodule off the external iliac vessels was successfully performed with adequate range of motion provided by the arms and without any complications. Trocar placement should be tailored to the site of surgical interest. Robotic-assisted laparoscopy should be considered as a valid alternative to the traditional open approach, when managing solitary masses in patients with recurrent ovarian cancer.

Parathyroidectomy versus Cinacalcet in the Management of Tertiary Hyperparathyroidism: Surgery Improves Renal Transplant Allograft Survival.

BACKGROUND: Renal transplant allograft function in patients with tertiary hyperparathyroidism who are treated with cinacalcet versus parathyroidectomy remains unclear. METHODS: This is a retrospective, single-center review of patients with tertiary hyperparathyroidism between 2000 and 2017. We compared clinical parameters and outcomes, including renal allograft failure in patients who had undergone parathyroidectomy versus treatment with cinacalcet therapy. RESULTS: A total of 133 patients were included (33 who received parathyroidectomy and 100 who received cinacalcet); median renal allograft survival was 5.9 years (interquartile range 4.0-9.0). There were no differences in age, sex, body mass index, comorbidities, duration of pretransplant dialysis, cadaveric donor utilization, or rates of delayed allograft function between cohorts. In the parathyroidectomy cohort, normalization of parathyroid hormone occurred more frequently (67% vs 15%, P < .001) and renal allograft failure rates were less (9% vs 33%, P = .007), with similar median posttransplant follow-up (7.0 years [interquartile range 4.5-10.0]). On multivariable analysis, parathyroidectomy was inversely associated with allograft failure (odds ratio 0.20, 95%-confidence interval 0.06-0.71, P = .013); there were no other associated factors. A greater median parathyroid hormone (pg/mL) 1 year posttransplant (348 [interquartile range 204-493] vs 195 [interquartile range 147-297], P = .025) was associated with allograft failure in the cinacalcet cohort. CONCLUSION: Parathyroidectomy for tertiary hyperparathyroidism is associated with lesser rates of renal allograft failure compared with cinacalcet management. Patients with inadequate parathyroid hormone control on cinacalcet at 1 year posttransplant should be considered for parathyroidectomy to prevent potential allograft failure.

Assessing Coagulation by Rotational Thromboelastometry (ROTEM) in Rivaroxaban-Anticoagulated Blood Using Hemostatic Agents.

Introduction The use of direct oral anticoagulants (DOACs) such as rivaroxaban (Xarelto) is increasingly common. However, therapies for reversing anticoagulation in the event of hemorrhage are limited. This study investigates the ability of hemostatic agents to improve the coagulation of rivaroxaban-anticoagulated blood, as measured by rotational thromboelastometry (ROTEM). Hypothesis/Problem If a chitosan-based hemostatic agent (Celox), which works independently of the clotting cascade, is applied to rivaroxaban-anticoagulated blood, it should improve coagulation by decreasing clotting time (CT), decreasing clot formation time (CFT), and increasing maximum clot firmness (MCF). If a kaolin-based hemostatic agent (QuikClot Combat Gauze), which works primarily by augmenting the clotting cascade upstream of factor Xa (FXa), is applied to rivaroxaban-anticoagulated blood, it will not be effective at improving coagulation. METHODS: Patients (age >18 years; non-pregnant) on rivaroxaban, presenting to the emergency department (ED) at two large, university-based medical centers, were recruited. Subjects (n=8) had blood drawn and analyzed using ROTEM with and without the presence of a kaolin-based and a chitosan-based hemostatic agent. The percentage of patients whose ROTEM parameters responded to the hemostatic agent and percent changes in coagulation parameters were calculated. RESULTS: Data points analyzed included: CT, CFT, and MCF. Of the samples treated with a kaolin-based hemostatic agent, seven (87.5%) showed reductions in CT, eight (100.0%) showed reductions in CFT, and six (75.0%) showed increases in MCF. The average percent change in CT, CFT, and MCF for all patients was 32.5% (Standard Deviation [SD]: 286; Range:-75.3 to 740.7%); -66.0% (SD:14.4; Range: -91.4 to -44.1%); and 4.70% (SD: 6.10; Range: -4.8 to 15.1%), respectively. The corresponding median percent changes were -68.1%, -64.0%, and 5.2%. Of samples treated with a chitosan-based agent, six (75.0%) showed reductions in CT, three (37.5%) showed reductions in CFT, and five (62.5%) showed increases in MCF. The average percent changes for CT, CFT, and MCF for all patients were 165.0% (SD: 629; Range:-96.9 to 1718.5%); 139.0% (SD: 174; Range: -83.3 to 348.0%); and -8.38% (SD: 32.7; Range:-88.7 to 10.4%), respectively. The corresponding median percent changes were -53.7%, 141.8%, and 3.0%. CONCLUSIONS: Rotational thromboelastometry detects changes in coagulation parameters caused by hemostatics applied to rivaroxaban-anticoagulated blood. These changes trended in the direction towards improved coagulability, suggesting that kaolin-based and chitosan-based hemostatics may be effective at improving coagulation in these patients. Bar J , David A , Khader T , Mulcare M , Tedeschi C . Assessing coagulation by rotational thromboelastometry (ROTEM) in rivaroxaban-anticoagulated blood using hemostatic agents. Prehosp Disaster Med. 2017;32(5):580-587.