Defining the pathogenicity of optineurin in juvenile open-angle glaucoma

PURPOSE: Juvenile open-angle glaucoma (JOAG) differs from primary open-angle glaucoma in that it is usually a more severe phenotype and has an earlier age of onset. Optineurin was recently associated with a variant of POAG that is characterized by intraocular pressure within normal limits: normal-tension glaucoma. The present study tested whether OPTN sequence changes play a role in early-onset glaucoma characterized by elevated intraocular pressure. METHODS: Sixty-six patients with JOAG characterized by high intraocular pressure were screened for mutations. Mutational analysis was performed with a combination of restriction enzyme digestion, single-strand conformation polymorphism, and direct sequencing. The effects of select changes on exon splicing were assessed using bioinformatic modeling approaches and RT-PCR. RESULTS: Ten sequence changes were identified, of which H486R was strongly suggestive of pathogenicity. H486R represents the first reported OPTN mutation associated with JOAG. Also, L41L is proposed to confer an increased susceptibility to the development of JOAG. Most of the other sequence changes observed were not thought to be biologically significant. The frequency of the previously reported M98K allele was not increased in the JOAG population studied but showed the previously reported skewed distribution in the POAG study population. The changes identified were not shown to affect the splicing machinery. CONCLUSIONS: The results of this work support the hypothesis that mutations in OPTN are not specifically associated with low-pressure glaucoma, but can play a role in JOAG.     

Hemodynamic stability,myocardial ischemia,and perioperative outcome after carotid surgery with remifentanil/propofol or isoflurane/fentanyl anesthesia

This study compares remifentanil/propofol (remi/prop) with isoflurane/fentanyl (iso/fen) anesthesia to determine which provides the greater hemodynamic stability, lesser myocardial ischemia, and morbidity with better postoperative outcomes after carotid endarterectomy. Sixty patients undergoing unilateral carotid endarterectomy were randomized to receive either a remi/prop or iso/fen anesthetic. Hemodynamic variables were recorded during the surgical procedure. In addition, transesophageal echocardiography was used to assess evidence of intraoperative regional wall motion abnormalities suggestive of cardiac ischemia. Emergence and extubation times, recovery from anesthesia, hemodynamic instability, nausea, vomiting, and pain in post anesthesia recovery, discharge delays, ICU admittance, hospital discharge, and preoperative and postoperative troponin levels were compared using appropriate statistical methods with P < 0.05 considered significant. The groups were demographically alike. Hemodynamic variables were similar during intubation and throughout surgery. Twenty-two percent of patients receiving iso/fen developed intraoperative regional wall motion abnormalities suggestive of ischemia, whereas no remi/prop patients had changes (P < 0.05). There was no difference in ST-T wave changes after surgery, and no patient had an elevation in troponin I levels. Postoperative variables were similar except that patients who received iso/fen had lower Stewart recovery scores during the first 15 minutes after post anesthesia care unit admission and a higher incidence of nausea and vomiting the day after surgery, whereas patients receiving remi/prop had discharge delays secondary to hypertension. ICU admittance, time to first void, oral intake, and time to hospital discharge were similar between the groups. At 9 times the cost of an iso/fen anesthesia technique, remi/prop offers little advantage over inhalational anesthesia for carotid endarterectomy.     

White paper on the health status of Asian Americans and Pacific Islanders and recommendations for research

A literature review of various reports sponsored by federal governmental agencies and proceedings of conferences of Asian Americans' and Pacific Islanders' health organizations provides data of health disparities among and between these diverse ethnic groups. Specifically, demographic and socio-economic data, as well as health care issues, are reported. Asian Americans and Pacific Islanders exceed other groups in health disparities in the area of tuberculosis and hepatitis B, whereas cancer and cardiovascular diseases are leading causes of death within the Asian American and Pacific Islander populations. Recommendations for areas of research are provided.     

The receptor tyrosine kinases: role in cancer progression

The last two decades have witnessed significant progress in the understanding of the basic mechanisms underlying tumor growth and metastasis. Receptor tyrosine kinases play a central role in cell proliferation and differentiation, cell survival, cell motility, invasion, and angiogenesis, all of which contribute to tumor progression. Alterations at the level of the receptor and its ligand lead to the activation of a number of signaling pathways, each of which may contribute to cancer progression. The dissection of the molecular changes associated with neoplastic growth have provided pharmaceutical companies with a range of targets for drug intervention. This article highlights the deregulation of receptor tyrosine kinases in human cancers and their involvement in metastasis.     

The role of angiogenic markers in adverse perinatal outcomes: fresh versus frozen embryo transfers

Purpose

We aimed to investigate the angiogenic balance in fresh compared to frozen embryo transfers, and among neonates with adverse perinatal outcomes.

Methods

This was a retrospective cohort study. All IVF cycles resulting in a singleton live birth at a university academic fertility center from January 1, 2011, to December 31, 2013, were examined. Concentrations of sFLT-1 and PlGF were measured in previously frozen serum specimens collected during early gestation at approximately 5 weeks gestation. Patients completed an electronic survey to detail perinatal outcome.

Results

We identified 152 singleton live births (103 fresh, 49 frozen). Demographic characteristics were similar between the two groups. Ratios of sFlt-1:PlGF were not different between fresh and frozen transfers. Neonates from fresh cycles had a mean birth weight 202 g lighter (p = 0.01) than frozen cycles, after adjusting for gestational age. Among babies born with poor perinatal outcomes, there was a difference in sFlt-1:PlGF ratios after adjusting for race. In non-Asians, infants born small for gestational age (SGA) (< 10th percentile) had significantly higher sFLT-1:PLGF ratio, median ratio (0.21 vs 0.12, p = 0.016).

Conclusions

Fresh transfers were associated with lower birth weight infants compared to frozen transfers. While there was no difference in sFlt-1:PlGF ratios between fresh and frozen transfers, these ratios were significantly lower in SGA infants, suggesting an imbalance in angiogenic markers during placentation.

     

Hysterectomy for the Transgender Man

Purpose of Review

Our objective is to summarize the most recent, high-quality data regarding perioperative recommendations for hysterectomy and salpingo-oophorectomy in transgender and gender nonconforming individuals.

Recent Findings

Many transgender men desire hysterectomy and salpingo-oophorectomy for gender affirmation, cancer-risk reduction, pelvic pain, or abnormal uterine bleeding. Gender-confirming hysterectomy is safe, effective, and highly beneficial for well-counseled patients. Preoperative considerations include optimizing the office environment, preoperative testing specific to patients with long-term testosterone use, counseling specific to transgender men, consideration of World Professional Association for Transgender Health criteria, and coordination of a multi-disciplinary team. Minimally invasive approaches, including vaginal, laparoscopic, and robotic-assisted hysterectomy, are the standard of care for cisgender women and transgender men given lower complication rates, better post-operative outcomes, and greater cosmetic satisfaction. Concurrent appendectomy, mastectomy, vaginectomy, and urethral reconstruction may be performed at the time of hysterectomy; phalloplasty and metoidioplasty are generally performed as subsequent procedures. Same-day discharge following hysterectomy is safe and has been shown to improve post-operative outcomes. We recommend follow-up with the patient’s mental health professional and endocrinologist in addition to routine surgical follow-up. Long-term satisfaction after genital surgery appears to be high and regret is low.

Summary

More robust and up to date research is needed to improve guidelines and perioperative care for transgender individuals. Available data suggests that hysterectomy and salpingo-oophorectomy for transgender men is safe, is not associated with any additional risks compared to cisgender women, and is associated with an improved quality of life.

     

Familial spontaneous complete heart block in hypertrophic cardiomyopathy

Two siblings with hypertrophic cardiomyopathy developed spontaneous complete heart block requiring permanent pacemaker implantation at similar ages (29 and 33 years). The clinical, morphological, and haemodynamic expressions of hypertrophic cardiomyopathy differed considerably in these two patients. The sister had severe functional limitation due to dyspnoea, pronounced and diffuse left ventricular hypertrophy (maximum ventricular septal thickness of 41 mm), and left ventricular outflow obstruction (peak subaortic gradient of 75 mm Hg under basal conditions). In contrast the brother was symptom free, had only modest left ventricular hypertrophy which was confined to the anterior ventricular septum (maximal thickness of 16 mm), and had no echocardiographic evidence of subaortic obstruction. These dissimilar findings in siblings with hypertrophic cardiomyopathy suggest that the predisposition to develop complete heart block was probably genetically transmitted, although it was unrelated to the phenotypic and clinical expression of the disease.