RHD maternal-fetal genotype incompatibility and schizophrenia: extending the MFG test to include multiple siblings and birth order

Rh incompatibility disease (ie Rh hemolytic disease of the fetus and newborn) has been implicated as a risk factor for schizophrenia. Here, we extend the maternal-fetal genotype incompatibility (MFG) test used in an earlier case-parent trio study that found significant evidence for an increased risk of schizophrenia in RHD MFG-incompatible children. We modify the MFG test for case-parent trios to include any number of siblings. This modified test enables us to use more of the available data from the earlier study. The increased sample size not only gives us greater power to test for MFG incompatibility but it also enables us to model the impact of previous RHD MFG-incompatible pregnancies on the relative risk of RHD MFG incompatibility in later-born siblings. This modeling is important, because RHD MFG incompatibility is a proxy for Rh incompatibility disease, and the risk of Rh incompatibility disease increases with the number of previous RHD MFG-incompatible pregnancies. The best-fitting models are consistent with the hypothesized effect that previous incompatible pregnancies increase the risk of schizophrenia due to RHD MFG incompatibility. There was significant evidence that the relative risk of schizophrenia in the second- and later-born RHD MFG-incompatible children is 1.7, consistent with earlier estimates. Our extension of the MFG test has general application to family-based studies of maternal-genotype and MFG interaction effects.     

Depression in women with polycystic ovary syndrome: clinical and biochemical correlates

BACKGROUND: We assessed the prevalence of mood disturbance among women with prospectively documented polycystic ovary syndrome (PCOS). METHODS: Thirty-two women with PCOS completed the Center for Epidemiological Studies-Depression Rating Scale (CES-D). Clinical and biochemical characteristics were assessed. RESULTS: Sixteen women had CES-D scores indicative of depression. Depression was associated with greater insulin resistance (P=0.02) and higher body mass index (P=0.05). Women receiving oral contraceptives for the treatment of PCOS were less depressed than patients not receiving treatment (P=0.03). LIMITATIONS: Possible selection bias, use of a screening tool alone without further diagnostic evaluation of depression, small samples size and lack of direct comparison with an age matched control group, should be considered in interpretation of these results. CONCLUSION: Findings suggest a high prevalence of depression among women with PCOS, and an association between depression and PCOS markers.     

Comparison of benign and malignant insulinoma

BackgroundHow malignant insulinomas present relative to benign insulinomas is unknown.MethodsA single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used.ResultsA total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01.ConclusionsLarger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.     

Is same-day discharge associated with increased 30-day postoperative complications and readmissions in patients undergoing laparoscopic adrenalectomy?

BackgroundAdvances in minimally invasive surgery and perioperative care have decreased substantially the duration of time that patients spend recovering in hospital, with many laparoscopic procedures now being performed on an ambulatory basis. There are limited studies, however, on same-day discharge after laparoscopic adrenalectomy. The objectives of this study were to investigate the outcomes and trends of ambulatory laparoscopic adrenalectomy in a multicenter cohort of patients.MethodsAdult patients who underwent elective laparoscopic adrenalectomy between 2005 and 2016 were identified in the database of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Baseline demographics and 30-day outcomes were compared between patients who underwent ambulatory laparoscopic adrenalectomy and those who were discharged after an inpatient stay. Multivariable logistic regression and Cox proportional hazards modelling were used to investigate the association between same-day discharge and 30-day complications and unplanned readmissions.ResultsOf the 4,807 patients included in the study, 88 (1.8%) underwent ambulatory laparoscopic adrenalectomy and 4,719 (98.2%) were admitted after the adrenalectomy. The same-day discharge group contained fewer obese patients (37.2% vs 50%; P = .04), a lesser proportion of American Society of Anesthesiologists class III patients (45.5% vs 61%; P = .003), and more patients with primary aldosteronism (14.8% vs 6%; P = .002) compared with the inpatient group. After adjustment for confounders, same-day discharge was not associated with 30-day overall complications (OR 1.17, 95% CI 0.35–3.85; P = .80) or unplanned readmissions (HR 2.77, 95% CI 0.86–8.96; P = .09). The percentage of laparoscopic adrenalectomies performed on an ambulatory basis at hospitals participating in the ACS NSQIP remained low throughout the study period (0–3.1% per year) with no evidence of an increasing trend over time (P = .21).ConclusionAmbulatory laparoscopic adrenalectomy is a safe and feasible alternative to inpatient hospitalization in selected patients. Further study is needed to determine the cost savings, barriers to uptake, and optimal selection criteria for this approach.     

Spiral ligament and stria vascularis changes in cochlear otosclerosis: effect on hearing level.

OBJECTIVE: To investigate the effect of changes within the spiral ligament and stria vascularis on hearing in cochlear otosclerosis, we examined spiral ligament hyalinization, stria vascularis atrophy, and sensory hearing loss in cochlear otosclerosis and described changes in ion transport molecule expression. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: Thirty-two cochleae from 24 temporal bone donors with histologic evidence of cochlear otosclerosis, including spiral ligament hyalinization. INTERVENTION: Audiography. MAIN OUTCOME MEASURES: Measurements of spiral ligament width, stria vascularis, and bone-conduction thresholds were compared by the amount of hyalinization. Expression of the ion transport molecules Na,K-ATPase, connexin 26, and carbonic anhydrase II were assessed by immunohistochemical techniques. RESULTS: Hyalinization most often involved the posterior basal turn (88%) and the posterior middle turn (27%). Spiral ligament hyalinization correlated significantly with stria vascularis atrophy in the posterior middle turn of the cochlea (rho = -0.63, p < 0.01). There was a trend toward a significant association in the posterior basal turn (rho = -0.31, p < 0.08). Bone-conduction thresholds at 2,000 and 4,000 Hz were significantly associated with the amount of stria vascularis atrophy (rho = -0.44, -0.40, p < 0.05). In addition, we observed decreased immunostaining for both carbonic anhydrase II with Type I fibrocytes and Na,K-ATPase with stria vascularis and Type II and Type IV fibrocytes of the spiral ligament in cochlear otosclerosis sections compared with normal cochlea. Na,K-ATPase staining within the stria vascularis was further decreased in the presence of spiral ligament hyalinization. No significant differences were seen with connexin 26 immunostaining. However, immunostaining results were somewhat inconsistent. CONCLUSION: These data suggest that spiral ligament structure and function are essential for stria vascularis survival. In addition, dampened expression of ion transport molecules within the spiral ligament and stria vascularis may disrupt potassium ion recycling, resulting in loss of endocochlear potential and sensory hearing loss.     

National Performance Measures for Diabetes Mellitus Care

When considering the trends in disease management, the focus of healthcare in the US has shifted from communicable diseases, which can most often be managed successfully, to chronic diseases, which are currently not managed very well. Chronic diseases, such as diabetes mellitus, become a lifelong health problem for the individual, the family, and in the workplace. Currently, there is no vaccine to prevent diabetes and no cure for diabetes once acquired. In order to improve the quality of care for diabetes, national performance measures have been developed to provide a unified set of diabetes-specific performance and outcome measures.The Diabetes Quality Improvement Project (DQIP) founded in 1997 through a partnership between the Center for Medicare and Medicaid Services, the National Committee for Quality Assurance, and the American Diabetes Association, established a single, standardized set of performance measures for diabetes care quality improvement and accountability in the US, which were published in 1998. The DQIP measures are noteworthy as a model for many other chronic diseases. Indeed, the DQIP represents the first widely adopted comprehensive performance measurement standards, not just for diabetes but for any single chronic disease. This is of further significance since it was developed by a coalition of public and private entities in the US.In order to prevent long-term complications from diabetes, there needs to be a physician-coordinated treatment plan involving a team approach to the problem. When such a physician-coordinated treatment plan is developed in conformance with the comprehensive performance measures, the prospects for a greater impact on diabetes might be enhanced.Overall, national performance measures for diabetes care have been widely adopted into health plan quality initiatives and have resulted in increased efforts to promote preventative screening and testing. Better compliance has lead to more stringent glucose control and helped to educate the public on the utility of the glycosylated hemoglobin level test for finding those at risk for microvascular and neuropathic complications. While more Americans with diabetes are receiving the recommended standards of care as a result of the implementation of national performance measures, diabetes management remains suboptimal but achievable.The authors concluded from this review that national performance measures have provided health plans and providers with objective tools to measure quality; however, these measures now need to move to prevention standards and initiatives. Policy development for diabetes care must continue to move from managing chronic illness to preventative screening of pre-diabetes through to identification and modification of lifestyle risk factors.     

A phase I and pharmacologic trial of two schedules of the proteasome inhibitor, PS-341 (bortezomib, velcade), in patients with advanced cancer.

PURPOSE: To define the toxicities, pharmacodynamics, and clinical activity of the proteasome inhibitor, PS-341 (bortezomib), in patients with advanced malignancies. PATIENTS AND METHODS: Twenty-eight patients (14 male and 14 female) received PS-341 twice weekly for 4 of 6 weeks (schedule I). Because toxicity necessitated dose omissions on this schedule, 16 additional patients (12 male and 4 female) received PS-341 twice weekly for 2 of every 3 weeks (schedule II). A total of 73 courses of treatment was given (median, 2; range, 1-4). Inhibition of 20S proteasome activity in peripheral blood mononuclear cells (PBMC) and accumulation of proteasome-targeted polypeptides in tumor tissue were evaluated as pharmacodynamic markers of PS-341 activity. RESULTS: The most common toxicity was thrombocytopenia, which was dose limiting at 1.7 mg/m2 (schedule I) and 1.6 mg/m2 (schedule II), respectively. Sensory neuropathy was dose-limiting in a patient in schedule I. Grade > or =3 toxicities for schedule I were constipation, fatigue, myalgia, and sensory neuropathy. Grade > or =3 toxicities for schedule II were dehydration resulting from diarrhea, nausea and vomiting, fatigue, hypoglycemia, and hypotension. The maximum tolerated dose was 1.5 mg/m2 for both schedules. Reversible dose-dependent decreases in 20S proteasome activity in PBMCs were observed, with 36% inhibition at 0.5 mg/m2, 52% at 0.9 mg/m2, and 75% at 1.25 mg/m2. Accumulation of proteasome-targeted polypeptides was detected in tumor samples after treatment with PS-341. A patient with multiple myeloma had a partial response. CONCLUSION: PS-341 given 1.5 mg/m2 twice weekly for 2 of every 3 weeks is well tolerated and should be further studied.