Serum testosterone levels and testosterone supplementation in cirrhosis: A systematic review.

BACKGROUND & AIMS: Cirrhosis disrupts the hypothalamic-pituitary-gonadal axis causing low testosterone. Testosterone deficiency is associated with sarcopenia and osteopenia, leading to a state of frailty and worse clinical outcomes, morbidity and mortality. We aimed to conduct a systematic review on the relationship between serum testosterone and laboratory, anthropometric and clinical outcomes in observational and interventional studies in cirrhosis. METHODS: PubMed and EMBASE were searched from inception through 27 August 2020 and reviewed independently by two investigators; a third reviewer solved disagreement. A qualitative summary of relevant findings was done. Methodological quality was assessed using the Newcastle Ottawa Scale for non-interventional studies and the Cochrane Risk of Bias for interventional studies. RESULTS: Out of 3569 articles, 15 met inclusion criteria with six observational studies of 1267 patients and nine interventional studies of 580 patients. In observational studies, low serum testosterone level was associated with sarcopenia, shorter median time to hepatic decompensation, transplant requirement, higher model for end-stage liver disease (MELD) scores, and death in cirrhotic patients. Nine interventional studies (361 treated with testosterone vs 219 placebo, 1-36 months) showed that testosterone supplementation improved serum testosterone, appendicular mass and bone mineral density. However, no trial reported improvement in liver-related scores, complications, readmission rates or death. CONCLUSIONS: Low serum testosterone is associated with increased morbidity and mortality in cirrhosis patients. Testosterone supplementation improved intermediate endpoints, but there was no conclusive data on clinical outcomes. Testosterone supplementation may be a promising strategy to improve frailty and decrease significant clinical complications in cirrhosis.

The Effect of Shift Work on Urogenital Disease: a Systematic Review.

PURPOSE OF REVIEW: Non-standard shift work schedules negatively impact the overall health of shift workers, and several studies have shown that shift work, specifically, is detrimental to urogenital health. The aims of this study are to systematically review the literature and determine the effect of shift work on the outcomes of hypogonadism, male infertility, lower urinary tract symptoms, and urogenital cancers. RECENT FINDINGS: Recent evidence supports associations between non-standard shift work and an increase in the frequency of prostate cancer and the severity of erectile dysfunction, lower urinary tract symptoms, and hypogonadal symptoms, as well as worsening of semen parameters and fertility. These associations are strengthened by the presence of shift work sleep disorder (SWSD) which affects up to 20% of shift workers. No studies have assessed the impact of shift work on the frequency or severity of nephrolithiasis, interstitial cystitis, pelvic pain, prostatitis, or urinary tract infections. Non-standard shift work has been associated with a variety of negative health outcomes and urologic complications, especially with concurrent shift work sleep disorder. Recognition of these elevated risks among shift workers can aid in more effective screening for urologic conditions.

Gadolinium-conjugated gold nanoshells for multimodal diagnostic imaging and photothermal cancer therapy.

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, gadolinium-conjugated gold nanoshells are engineered and it is demonstrated that they enhance contrast for magnetic resonance imaging, X-ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation.

The Relationship Between Shift Work and Men's Health.

BACKGROUND: More than 21 million Americans and nearly 20% of the U.S. workforce are shift workers. Non-standard shift work, defined as work that falls outside of 6 am-6 pm, can lead to poor diet, exercise, and sleep habits that lead to decreased productivity, increased workplace accidents, and a variety of negative health outcomes. AIM: To investigate the associations between shift work exposure and chronic medical conditions such as metabolic syndromes, cardiovascular disease, gastrointestinal disturbances, and depression as well as urologic complications including hypogonadism, male infertility, lower urinary tract symptoms, and prostate cancer with a focus on the effects of shift work sleep disorder (SWSD) on the severity of these negative health outcomes. METHODS: We reviewed the literature examining effects of shift work and SWSD on general and urologic health. OUTCOMES: We produced a summary of effects of shift work on health with focus on the increased risk of negative health outcomes in non-standard shift workers, particularly those with SWSD, when compared to daytime workers or workers without SWSD. RESULTS: Studies have associated non-standard shift work schedules and poor health outcomes, including increased risks of diabetes mellitus, dyslipidemia, hypertension, heart disease, peptic ulcer disease, and depression, in shift workers. However, few studies have focused on the role that shift work plays in men's urologic health. Current evidence supports associations between non-standard shift work and increased hypogonadal symptoms, poor semen parameters, decreased fertility, lower urinary tract symptoms, and prostate cancer. These associations are strengthened by the presence of SWSD, which affects up to 20% of shift workers. Unfortunately, interventions, such as planned naps, timed light exposure, melatonin, and sedative hypnotics, aimed at alleviating excessive nighttime sleepiness and daytime insomnia in non-standard shift workers experiencing SWSD, are limited and lack strong evidence to support their efficacy. CONCLUSIONS: Non-standard shift work has been associated with a variety of negative health outcomes and urologic complications, especially with concurrent SWSD. Recognition of these increased risks among shift workers can potentially aid in more effective screening of chronic health and urologic conditions. Non-pharmacologic treatment of SWSD focuses on behavioral therapy and sleep hygiene while melatonin, hypnotics, and stimulants are used to alleviate insomnia and excessive sleepiness of SWSD. Further research into both pharmacologic and non-pharmacologic therapies for SWSD is needed to establish more definitive guidelines in the treatment of SWSD in order to increase productivity, minimize workplace accidents, and improve quality of life for shift workers. Deng N, Kohn TP, Lipshultz LI, et al. The Relationship Between Shift Work and Men's Health. Sex Med Rev 2018;6:446-456.

Heart rate variability changes and its association with the development of severe retinopathy of prematurity.

PURPOSE: To evaluate differences in autonomic nervous system (ANS) activity associated with the development of retinopathy of prematurity. METHODS: Heart rate variability (HRV) as an indicator of ANS activity was calculated in two groups of premature infants: (1) a treatment group of infants who developed type 1 ROP and underwent treatment and (2) a control group of infants who did not develop ROP more severe than stage 1 and who were matched to the treatment group in terms of age, weight, and similar risk factors, including similar frequency of intraventricular hemorrhage, bronchopulmonary dysplasia, and sepsis. HRV was analyzed during the first 5 days of life, within 5 days of initial ROP examination, and within 5 days of ROP treatment for the treatment group or, for controls, on the day of last electrocardiogram data prior to discharge. Calculations were performed for the high frequency, low frequency, and low frequency-high frequency values of the HRV components for all infants. RESULTS: Between the initial ophthalmologic evaluation and the final evaluation, there was a tendency for reduction in both the low- and high-frequency components of the HRV indices in the treatment group, whereas there was a tendency for an increase in both components of the HRV indices in the control group. The difference in the rate of change of the high frequency between groups was statistically significant (P = 0.021). CONCLUSIONS: Disruption in ANS activity may play an important role in the development and severity of ROP.

Sexual dysfunction and infertility in the male spina bifida patient.

Spina bifida is a congenital neural tube defect with many neurological implications, as well as decreased sexual function and infertility. Few studies have directly investigated infertility in men with spina bifida. Infertility in this special patient population is primarily the result of spermatogenic defects and/or failure of sperm transport due to erectile or ejaculatory dysfunction. The severity of sexual and reproductive dysfunction seems to correlate with higher level of spina cord lesion and presence of hydrocephalus. Phosphodiesterase 5 inhibitors (PDE5is) have been shown to be effective for erectile dysfunction in some men with spina bifida. Surgical sperm retrieval from the genitourinary tract and rectal probe electroejaculation can serve as methods for collecting sperm from those with ejaculatory dysfunction or retrograde ejaculation. Assisted reproductive technology such as intracytoplasmic sperm injection allows isolated sperm from men with infertility to achieve fertilization. Since most spina bifida patients are surviving into adolescence and adulthood due to improved medical and surgical advancements, it is paramount for healthcare professionals to address issues related their sexual and reproductive function.

HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer.

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.