Glucocorticoids and Water Balance: Implications for Hyponatremia Management and Pituitary Surgery.

Water balance is fundamental to all homeostasis. The hypothalamic-pituitary-adrenal axis influences water balance through the effects of corticotropin-releasing hormone and cortisol on arginine vasopressin secretion and the peripheral effects of cortisol on hemodynamics and renal water handling. In this review, we explored the complex interplay of glucocorticoids with water balance, with particular attention to hyponatremia and pituitary surgery.

Measuring Quality of Life in Chronic Limb-threatening Ischemia Patients and Informal Carers: A Scoping Review.

OBJECTIVE: To review quality of life (QOL) instruments for chronic limb-threatening ischemia (CLTI) patients and informal carers, and their use in QOL and cost-utility analysis (CUA) studies. BACKGROUND: CLTI is a global health problem with significant morbidity affecting patients and informal carers. QOL is increasingly measured for holistic outcomes assessment and CUA. However, measurement instruments in CLTI are poorly understood. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, COSMIN, PROQOLID, CEA registry, and NHS EED databases were searched for all English language studies up to May 2021. Features of instruments, evidence of measurement property appraisal, and trends in use were assessed. Prospective protocol registration (Open Science Framework: https://doi.org/10.17605/OSF.IO/KNG9U ). RESULTS: A total of 146 studies on QOL instruments (n=43), QOL outcomes (n=97), and CUA (n=9) were included. Four disease-specific QOL instruments are available for lower extremity arterial disease (intermittent claudication or CLTI). VascuQoL-25 and VascuQoL-6 have been used in CLTI. There is no CLTI-specific instrument. Of 14 generic instruments, SF-36, EQ-5D-3L, NHP, and WHOQOL-BREF were most common. Studies reporting partial measurement property appraisal favored VascuQoL-25, VascuQoL-6, and SF-36. Feasibility considerations include mode of administration and responder burden. None of 4 available carer-specific instruments have been used in CLTI. Since 1992, the number of QOL studies has increased considerably, but CUA studies are scarce. Informal carers have not been assessed. CONCLUSIONS: This review provides a comprehensive reference for QOL measurement in CLTI that helps end-users with instrument selection, use, and interpretation. However, a CLTI-specific instrument is needed. There is an opportunity to benefit society through future CUA studies and evaluation of QOL in informal carers.

Validation of the anterior skull base questionnaire 35 in endoscopic pituitary adenoma surgery.

Patient quality of life (QOL) is an important metric of surgical success. To guide therapeutic advances in pituitary adenoma surgery, a validated, comprehensive instrument to quantify QOL is required. We aim to evaluate the validity of the 35 item anterior skull base questionnaire (ASBQ-35) in patients undergoing pituitary adenoma surgery. A total of 168 patients undergoing endoscopic resection of pituitary adenomas underwent longitudinal QOL assessment using the ASBQ-35 and the 22-item Sinonasal Outcomes Test (SNOT-22) over the first postoperative year. Validity of the ASBQ-35 was assessed by internal consistency, test-retest reliability, responsiveness to clinical change, and concurrent validity with the SNOT-22. Internal consistency of the ASBQ-35 was excellent, with a Cronbach's alpha > 0.95 across all timepoints. Test-retest reliability between 3 and 6 months (ICC = 0.82, p < 0.001) and 6 months and 12 months (ICC = 0.78, p < 0.001) was robust. Concurrent validity with SNOT-22 was strong across all timepoints (absolute Pearson r ≥ 0.63, p < 0.001). Mean ASBQ-35 scores were significantly worse at 3 weeks compared to preoperative baseline (mean difference - 0.28, p < 0.01); however, by 12 months, scores had significantly improved (mean difference + 0.24, p < 0.01), indicating that the scale is responsive to clinical change. Each of the 6 domains of the ASBQ, and all 35 component questions, contributed to the discriminative of the ASBQ to measure QOL during the first postoperative year. The ASBQ-35 is a valid, comprehensive tool for assessing QOL after endoscopic pituitary adenoma surgery. Each component of the ASBQ-35 contributed to the overall assessment of QOL during the first postoperative year.

Intensification with dipeptidyl peptidase-4 inhibitor, insulin, or thiazolidinediones and risks of all-cause mortality, cardiovascular diseases, and severe hypoglycemia in patients on metformin-sulfonylurea dual therapy: A retrospective cohort study.

BACKGROUND: Although patients with type 2 diabetes mellitus (T2DM) may fail to achieve adequate hemoglobin A1c (HbA1c) control despite metformin-sulfonylurea (Met-SU) dual therapy, a third-line glucose-lowering medication-including dipeptidyl peptidase-4 inhibitor (DPP4i), insulin, or thiazolidinedione (TZD)-can be added to achieve this. However, treatment effects of intensification with the medications on the risk of severe hypoglycemia (SH), cardiovascular disease (CVD), and all-cause mortality are uncertain. Study aim was to compare the risks of all-cause mortality, CVD, and SH among patients with T2DM on Met-SU dual therapy intensified with DPP4i, insulin, or TZD. METHODS AND FINDINGS: We analyzed a retrospective cohort data of 17,293 patients with T2DM who were free from CVD and on Met-SU dual therapy and who were intensified with DPP4i (n = 8,248), insulin (n = 6,395), or TZD (n = 2,650) from 2006 to 2017. Propensity-score weighting was used to balance out baseline covariates across groups. Hazard ratios (HRs) for all-cause mortality, CVD, and SH were assessed using Cox proportional hazard models. Mean age of all patients was 58.56 ± 11.41 years. All baseline covariates achieved a balance across the 3 groups. Over a mean follow-up period of 34 months with 49,299 person-years, cumulative incidences of all-cause mortality, SH, and CVD were 0.061, 0.119, and 0.074, respectively. Patients intensified with insulin had higher risk of all-cause mortality (HR = 2.648, 95% confidence interval [CI] 2.367-2.963, p < 0.001; 2.352, 95% CI 2.123-2.605, p < 0.001) than those intensified with TZD and DPP4i, respectively. Insulin users had the greatest risk of SH (HR = 1.198, 95% CI 1.071-1.340, p = 0.002; 1.496, 95% CI 1.342-1.668, p < 0.001) compared with TZD and DPP4i users, respectively. Comparing between TZDs and DPP4i, TZDs were associated with a higher risk of SH (HR = 1.249, 95% CI 1.099-1.419, p < 0.001) but not all-cause mortality (HR = 0.888, 95% CI 0.776-1.016, p = 0.084) or CVD (HR = 1.005, 95% CI 0.915-1.104, p = 0.925). Limitations of this study included the lack of data regarding lifestyle, drug adherence, time-varying factors, patients' motivation, and cost considerations. A limited duration of patients intensifying with TZD might also weaken the strength of study results. CONCLUSIONS: Our results indicated that, for patients with T2DM who are on Met-SU dual therapy, the addition of DPP4i was a preferred third-line medication among 3 options, with the lowest risks of mortality and SH and posing no increased risk for CVD events when compared to insulin and TZD. Intensification with insulin had the greatest risk of mortality and SH events.

Quality of Life in Craniopharyngioma: A Systematic Review.

BACKGROUND: Craniopharyngiomas are morbid tumors that significantly reduce patients' quality of life (QoL). The lifelong burden of endocrine, visual, hypothalamic, and limbic dysfunction can have disastrous consequences for the physical and psychosocial health of patients. Elucidating the factors that influence QoL could guide therapeutic interventions to improve patient well-being. METHODS: A systematic review was performed in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement using the PubMed and Medline databases. Studies that had reported patient QoL using validated metrics in both adult and pediatric populations were included. Bias and methodological rigor were assessed using the MINORS (methodological index for nonrandomized studies) criteria. RESULTS: A total of 25 studies, including 2025 patients, were available for review. Most studies were small, retrospective, cohort studies with a high risk of bias. The QoL of the patients with craniopharyngioma was lower than that of the general population. Hypothalamic involvement was consistently the strongest predictor of QoL. Endocrinopathy contributed to morbidity but could be ameliorated by hormone replacement therapy. Social and emotional dysregulation and a poor memory are common complaints after surgery, and iatrogenic damage to the infundibulum, hypothalamus, limbic system, and frontal lobes might underlie these concerns. Sleep-wake cycle dysfunction and hypothalamic obesity are serious consequences of hypothalamic damage. CONCLUSIONS: An experienced multidisciplinary team is necessary to optimally manage the complex cases of these patients. The poor QoL of patients with craniopharyngioma is multifactorial. However, the contribution of iatrogenesis is not insubstantial. Improved surgical techniques, focusing on hypothalamic preservation, and adjuvant treatment options are required to improve the well-being of these patients.

Postoperative fluid restriction to prevent hyponatremia after transsphenoidal pituitary surgery: An updated meta-analysis and critique.

BACKGROUND: Hyponatremia is a common and potentially dangerous complication of transsphenoidal surgery. Prophylactic postoperative fluid restriction has been trialled as a method to reduce the incidence of postoperative hyponatremia. METHODS: A systematic review of the literature was performed in accordance with the PRISMA statement. Risk of bias was assessed using the MINORS criteria. Meta-analysis was performed using the random-effects model. RESULTS: A total of 6 retrospective cohort studies were available for analysis. Fluid restriction was commonly between 1000 and 1500 ml/day and limited to the first postoperative week. Overall, the rate postoperative hyponatremia was fourfold less in the fluid restricted cohorts (3.4 % vs 11.2 %, OR 0.24 (95 %CI 0.15-0.38), p < 0.01). There was no difference in readmission rates (1.4 % vs 3.9 %, OR 0.32 (95 %CI 0.09-1.13), p = 0.08) or postoperative diabetes insipidus (14.5 % vs 18.6 %, OR 0.82 (95 %CI 0.50-1.36), p = 0.45) between fluid restricted and control cohorts. CONCLUSION: Prophylactic postoperative fluid restriction is a cheap, easily implemented intervention that appears to reduce the rate of postoperative hyponatremia, but not necessarily re-admission rates. Whether these prevented cases of hyponatremia are clinically significant remains to be demonstrated.

Ex vivo foam cell formation is enhanced in monocytes from older individuals by both extrinsic and intrinsic mechanisms.

Aging is the strongest predictor of cardiovascular diseases such as atherosclerosis, which are the leading causes of morbidity and mortality in elderly men. Monocytes play an important role in atherosclerosis by differentiating into foam cells (lipid-laden macrophages) and producing atherogenic proinflammatory cytokines. Monocytes from the elderly have an inflammatory phenotype that may promote atherosclerotic plaque development; here we examined whether they are more atherogenic than those from younger individuals. Using an in vitro model of monocyte transmigration and foam cell formation, monocytes from older men (median age [range]: 75 [58-85] years, n=20) formed foam cells more readily than those of younger men (32 [23-46] years, n=20) (P<0.003) following transmigration across a TNF-activated endothelial monolayer. Compared to young men, monocytes from the elderly had impaired cholesterol efflux and lower expression of regulators of cholesterol transport and metabolism. Foam cell formation was enhanced by soluble factors in serum from older men, but did not correlate with plasma lipid levels. Of the three subsets, intermediate monocytes formed the most foam cells. Therefore, both cellular changes to monocytes and soluble plasma factors in older men primes monocytes for foam cell formation following transendothelial migration, which may contribute to enhanced atherosclerosis in this population.

Monocytes from HIV-infected individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration.

DESIGN: HIV-infected (HIV+) individuals have an increased risk of atherosclerosis and cardiovascular disease which is independent of antiretroviral therapy and traditional risk factors. Monocytes play a central role in the development of atherosclerosis, and HIV-related chronic inflammation and monocyte activation may contribute to increased atherosclerosis, but the mechanisms are unknown. METHODS: Using an in-vitro model of atherosclerotic plaque formation, we measured the transendothelial migration of purified monocytes from age-matched HIV+ and uninfected donors and examined their differentiation into foam cells. Cholesterol efflux and the expression of cholesterol metabolism genes were also assessed. RESULTS: Monocytes from HIV+ individuals showed increased foam cell formation compared with controls (18.9 vs. 0%, respectively, P = 0.004) and serum from virologically suppressed HIV+ individuals potentiated foam cell formation by monocytes from both uninfected and HIV+ donors. Plasma tumour necrosis factor (TNF) levels were increased in HIV+ vs. control donors (5.9 vs. 3.5 pg/ml, P = 0.02) and foam cell formation was inhibited by blocking antibodies to TNF receptors, suggesting a direct effect on monocyte differentiation to foam cells. Monocytes from virologically suppressed HIV+ donors showed impaired cholesterol efflux and decreased expression of key genes regulating cholesterol metabolism, including the cholesterol transporter ABCA1 (P = 0.02). CONCLUSION: Monocytes from HIV+ individuals show impaired cholesterol efflux and are primed for foam cell formation following transendothelial migration. Factors present in HIV+ serum, including elevated TNF levels, further enhance foam cell formation. The proatherogenic phenotype of monocytes persists in virologically suppressed HIV+ individuals and may contribute mechanistically to increased atherosclerosis in this population.