The primary aim of this study was to compare the prevalence of subclinical hypothyroidism (SCH) using two different cut-off levels for TSH values (≥2.5 mIU/L versus ≥4.1 mIU/L). The secondary objective was to analyze the clinical-biochemical characteristics in women with and without SCH. This was a retrospective cross-sectional study. In total, 1496 Mexican women with infertility were included: Group 1, women with TSH levels ranging between 0.3 and 2.49 mIU/L, n = 886; Group 2, women with TSH between 2.5 and 4.09 mIU/L, n = 390; and Group 3, women with TSH ≥4.1 mIU/L n = 220. SCH prevalence was 40.7% (CI 95%: 38.3-43.3%) with TSH cut-off ≥ 2.5 mIU/L, and 14.7% (CI 95%: 12.7-16.5%) with TSH cut-off ≥ 4.1 mIU/L, (p = 0.0001). The prevalence of overweight was higher in Group 2 than in Groups 1 and 3. Thyroid autoimmunity, obesity and insulin resistance were higher in Group 3 than in Group 1 (p < 0.05). No other differences were observed between groups. Conclusions: The prevalence of SCH in our selected patients increased almost three times using a TSH cut-off ≥ 2.5 mIU/L compared with a TSH cut-off ≥ 4.1 mIU/L. Women with TSH ≥4.1 mIU/L compared with TSH cut-off ≤ 2.5 mIU/L more often presented with obesity, thyroid autoimmunity and insulin resistance.

https://www.mdpi.com/2075-4418/11/3/417/pdf

Effect of the Cut-Off Level for Thyroid-Stimulating Hormone on the Prevalence of Subclinical Hypothyroidism among Infertile Mexican Women

ABSTRACT The coexistence of osteoporosis and chronic kidney disease (CKD) is an evolving healthcare challenge in the face of increasingly aging populations. Globally, accelerating fracture incidence causes disability, impaired quality of life and increased mortality. Consequently, several novel diagnostic and therapeutic tools have been introduced for treatment and prevention of fragility fractures. Despite an especially high fracture risk in CKD, these patients are commonly excluded from interventional trials and clinical guidelines. While management of fracture risk in CKD has been discussed in recent opinion-based reviews and consensus papers in the nephrology literature, many patients with CKD stages 3–5D and osteoporosis are still underdiagnosed and untreated. The current review addresses this potential treatment nihilism by discussing established and novel approaches to diagnosis and prevention of fracture risk in patients with CKD stages 3–5D. Skeletal disorders are common in CKD. A wide variety of underlying pathophysiological processes have been identified, including premature aging, chronic wasting, and disturbances in vitamin D and mineral metabolism, which may impact bone fragility beyond established osteoporosis. We discuss current and emerging concepts of CKD–mineral and bone disorders (CKD-MBD) and integrate management of osteoporosis in CKD with current recommendations for management of CKD-MBD. While many diagnostic and therapeutic approaches to osteoporosis can be applied to patients with CKD, some limitations and caveats need to be considered. Consequently, clinical trials are needed that specifically study fracture prevention strategies in patients with CKD stages 3–5D.

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Management of fracture risk in CKD—traditional and novel approaches

1. Department of Medical Education, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. Vasco de Quiroga # 15, Belisario Domínguez Sección XVI, Tlalpan, Mexico City, 14080, Mexico. Email: [email protected]; Phone: 55 5487 0900. 2. Division of Postgraduate Studies, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico. 3. Metabolic Diseases Research Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. Financial support: none. Data availability statement: no new data was used for this manuscript. Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing interests: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: Not applicable. * Corresponding author 

Uneven resources threaten causal consistency in randomized trials

Alzheimer’s disease (AD) is a life-changing condition whose etiology is explained by several hypotheses. Recently, a new virus contributed to the evidence of viral involvement in AD: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 coronavirus disease. AD was found to be one of the most common COVID-19 comorbidities, and it was found to increase mortality from this disease as well. Moreover, AD patients were observed to present with the distinct clinical features of COVID-19, with delirium being prevalent in this group. The SARS-CoV-2 virus enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is overexpressed in brains with AD, which thus increases the viral invasion. Furthermore, the inhibition of the ACE2 receptor by the SARS-CoV-2 virus may also decrease the brain-derived neurotrophic factor (BDNF), contributing to neurodegeneration. The ApoE ε4 allele, which increases the risk of AD, was found to facilitate the SARS-CoV-2 entry into cells. Furthermore, the neuroinflammation and oxidative stress existing in AD patients enhance the inflammatory response associated with COVID-19. Moreover, pandemic and associated social distancing measures negatively affected the mental health, cognitive function, and neuro-psychiatric symptoms of AD patients. This review comprehensively covers the links between COVID-19 and Alzheimer’s disease, including clinical presentation, molecular mechanisms, and the effects of social distancing.

/pdf/links-between-covid-19-and-alzheimers-disease-what-do-we-1vn88ubi.pdf

Links between COVID-19 and Alzheimer’s Disease—What Do We Already Know?

Urinary iodine concentration (UIC) is routinely used to evaluate the population iodine status while the uniform method for the individual level assessment is uncertain.To explore the 24-h urinary iodine excretion (UIE) in five different periods of the day and the corresponding prediction equations respect by the use of creatinine-corrected UIC.We collected 24-h, spot and fasting urine in five periods of the day to estimate 24-h UIE by the six different prediction equations. We compared the estimated creatinine-corrected UIC to the collected 24-h UIE and identified the most suitable equations in each period of the day.Among the six different prediction equations, the equation of Kawasaki T was the best to estimate the 24-h UIE by fasting urine among Chinese adults. Among the five periods of time, the equation of Knudsen N was the best to estimate the 24-h UIE in the non-morning period.Urinary iodine status at the individual level could be estimated by different creatinine-based equations at different periods of the day. 

/pdf/is-the-urinary-iodine-creatinine-ratio-applicable-to-assess-g7imdqeh.pdf

Is the urinary iodine/creatinine ratio applicable to assess short term individual iodine status in Chinese adults? Comparison of iodine estimates from 24-h urine and timed-spot urine samples in different periods of the day

Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19.We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described.We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively).Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19. 

/pdf/pyridostigmine-reduces-mortality-of-patients-with-severe-21wp2ygl.pdf

Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial

Background The 2017 KDIGO guidelines establish a 2B grade recommendation in favor of testing Bone Mineral Density (BMD) by DXA to assess osteoporotic fracture (OPF) risk in patients with CKD G3a-G5D. Still, controversy remains because large studies evaluating it for this particular population are lacking. Aim To establish the clinical performance of BMD measured by DXA in the evaluation of fracture risk in women with CKD. Methods We conducted a 43 year retrospective cohort study with 218 women ≥18 years-old with CKD and BMD measurement by DXA of total hip and lumbar spine. Clinical (age, year of CKD onset, comorbidities, BMI, transplant status, treatment), and biochemical (PTH, corrected calcium, phosphate, vitamin D [25 (OH) D3], creatinine, and albumin), parameters were collected from hospital records. All osteoporotic fractures (as defined by the WHO) found in the clinical and radiologic files were registered. Results 218 women with a median age of 60 years (40–73 IQ range) and a CKD evolution time of 12 years (7–18 IQ range) were evaluated. Forty-eight (28.23%) presented an OPF. These women were older (57 vs 69 years, p =0.0072) and had a lower BMD. CKD stage did not influence fracture incidence. In the multivariate analysis we found that for each standard deviation decrease in hip and lumbar spine T-Score, the overall fracture risk was 2.7 and 2.04 times higher, respectively. More than 50% of fractures took place within the first ten years of follow-up, especially with GFR Conclusions BMD measured by DXA is a useful fracture prediction tool for women with CKD, having a sensibility and specificity similar to that in the general population. It seems to be appropriate for the diagnosis, treatment decisions, and follow-up of patients with renal failure.

Evaluation of bone densitometry by dual-energy x-ray absorptiometry as a fracture prediction tool in women with chronic kidney disease.

The aim of this study was to evaluate the prevalence of thyroid dysfunction in a cohort of healthy individuals in Mexico City, as well as to investigate the potential associations of these results with their estimated iodine intake (EII) as reflected by their 24-hour urinary iodine excretion (24-h UIE). From the SALMEX cohort, 683 adults provided an appropriate 24-h urine sample. Thyroid function tests and thyroid antibody concentrations were determined in the participants’ sera. We analyzed discrepancies between the commonly used urinary parameters to determine the iodine intake status and the performance of thyroglobulin (Tg) as a biomarker of its status in the adult population. The prevalence of dysthyroidism was high, being similar to other studies. Subclinical hypothyroidism was detected in 5.0% of individuals, clinical hypothyroidism in 1.8% of individuals, and sub-clinical hyperthyroidism in 2.8% of individuals. The median EII was 285 μg/d (IQR 215.0–369.0); 94% of individuals had EII >150 µg/d recommended daily allowance (RDA) in adults. The urinary iodine concentration (UIC) and the UIE had relative biases in their averages of 34.4%. The Tg median was 7.21 ng/mL. The prevalence of increased Tg was 6.15%. There was no correlation between Tg and EII (r= 0.019, p= 0.606). Thyroid dysfunction was highly prevalent in this population. Our cohort revealed a slight discrepancy between dysthyroidism manifestations and iodine intake markers; the latter represent a population with adequate iodine intake. Further studies are necessary to clearly define the prevalence of thyroid dysfunction as well as the iodine nutritional status in Mexico.

Sergio L. Carbajal-Morelos

Papers

Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial

Evaluation of bone densitometry by dual-energy x-ray absorptiometry as a fracture prediction tool in women with chronic kidney disease.

Prevalence of thyroid dysfunction in healthy adults according to the estimated iodine intake in 24-hour urine samples: The SALMEX cohort.