Diagnostic Values of Intraoperative (1-84) Parathyroid Hormone Levels are Superior to Intact Parathyroid Hormone for Successful Parathyroidectomy in Patients With Chronic Kidney Disease

ObjectivePersistent secondary hyperparathyroidism (SHPT) may occur because of residual cervicothoracic parathyroids in parathyroidectomy (PTX) patients with chronic kidney disease. We prospectively compared the predictive values of intraoperative plasma (1-84) parathyroid hormone (PTH) and intact PTH (iPTH) levels to improve the safety and efficacy of PTX.MethodsWe included 100 healthy controls, 162 stage 5 chronic kidney disease patients without SHPT, and 214 patients who underwent PTX because of SHPT. Plasma iPTH and (1-84) PTH levels were measured before incision (io-iPTH0 and io-[1-84]PTH0, respectively) and 10 minutes (io-iPTH10 and io-[1-84]PTH10, respectively) and 20 minutes (io-iPTH20 and io-[1-84]PTH20, respectively) after removing all parathyroids. The percentage reduction of iPTH and (1-84) PTH at 10 minutes (io-iPTH10% and io-[1-84]PTH10%, respectively) and 20 minutes (io-iPTH20%, and io-[1-84]PTH20%, respectively) was calculated. iPTH and (1-84) PTH were measured using second- and third-generation PTH assays, respectively.ResultsCompared with the controls and non-PTX patients, the PTX group had more obvious mineral metabolism disorders. There were 187 successful PTXs, 19 patients with persistent SHPT, and 8 patients lost to follow-up. The receiver operating characteristic curves revealed that io-(1-84)PTH10% >86.6% and io-(1-84)PTH20% >87.5% suggested successful PTX. The sensitivity of io-iPTH20% and io-(1-84)PTH20% were higher than those at the timepoint of 10 minutes. Moreover, the specificity and sensitivity of the (1-84) PTH reduction percentage were superior to that of iPTH.ConclusionIntraoperative reduction percentages of plasma (1-84) PTH levels are superior to iPTH for accurately predicting successful PTX, especially at 20 minutes after all cervicothoracic parathyroids had been resected.     

Association of Parathyroidectomy With 5-Year Clinically Significant Kidney Stone Events in Patients With Primary Hyperparathyroidism

ObjectivePatients with primary hyperparathyroidism (PHPT) are at increased risk of kidney stones. Guidelines recommend parathyroidectomy in patients with PHPT with a history of stone disease. This study aimed to compare the 5-year incidence of clinically significant kidney stone events in patients with PHPT treated with parathyroidectomy versus nonoperative management.MethodsWe performed a longitudinal cohort study of patients with PHPT in a national commercial insurance claims database (2006-2019). Propensity score inverse probability weighting-adjusted multivariable regression models were calculated.ResultsWe identified 7623 patients aged ≥35 years old with continuous enrollment >1 year before and >5 years after PHPT diagnosis. A total of 2933 patients (38.5%) were treated with parathyroidectomy. The cohort had a mean age of 66.5 years, 5953 (78.1%) were female, and 5520 (72.4%) were White. Over 5 years, the unadjusted incidence of ≥1 kidney stone event was higher in patients who were managed with parathyroidectomy compared with those who were managed nonoperatively overall (5.4% vs 4.1%, respectively) and among those with a history of kidney stones at PHPT diagnosis (17.9% vs 16.4%, respectively). On multivariable analysis, parathyroidectomy was associated with no statistically significant difference in the odds of a 5-year kidney stone event among patients with a history of kidney stones (odds ratio, 1.03; 95% CI, 0.71-1.50) or those without a history of kidney stones (odds ratio, 1.16; 95% CI, 0.84-1.60).ConclusionBased on this claim analysis, there was no difference in the odds of 5-year kidney stone events in patients with PHPT who were treated with parathyroidectomy versus nonoperative management. Time horizon for benefit should be considered when making treatment decisions for PHPT based on the risk of kidney stone events.     

Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19

ObjectiveTo explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsThe study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate.ResultsCompared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023).ConclusionAmong critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes.     

Impact of Pancreatic Neuroendocrine Tumor on Mortality in Patients With von Hippel-Lindau Disease

ObjectiveThe main causes for morbidity and mortality in von Hippel-Lindau (VHL) disease are central nervous system hemangioblastoma and clear cell renal cell carcinoma, but the effect of VHL-related pancreatic neuroendocrine tumors (PNET) on patient outcome is unclear. We assessed the impact of PNET diagnosis in patients with VHL on all-cause mortality (ACM) risk.MethodsWe used the Surveillance, Epidemiology, and End Results database. Of 16 344 patients, 170 had VHL based on clinical diagnostic criteria, and 510 patients had PNET (91 VHL-related and 419 sporadic).ResultsSurvival analysis demonstrated a lower ACM among patients with VHL-related PNET compared to patients with sporadic PNET (log-rank test, P = .011). Among patients with VHL, ACM risk was higher with vs without PNET (P = .029). The subgroup analysis revealed a higher ACM risk with metastatic PNET (sporadic P = .0031 and VHL-related P = .08) and a similar trend for PNET diameter ≥3 cm (P = .06 and P = 0.1 in sporadic and VHL-related PNET, respectively). In a multivariable analysis of patients with VHL, diagnosis with PNET by itself was associated with a trend of lower risk for ACM, while presence of metastatic PNET was independently associated with increased ACM risk.ConclusionDiagnosis with PNET is not associated with a higher ACM risk in VHL by itself. The independent association of advanced PNET stage with higher mortality risk emphasizes the importance of active surveillance for detecting high-risk PNET at an early stage to allow timely intervention.     

Predictors of Mortality in Hypercalcemia of Advanced Chronic Liver Disease

ObjectiveHypercalcemia is sometimes observed in patients with cirrhosis, but very little is known about the epidemiology in patients with hypercalcemia of chronic liver disease (HCLD) or how its presence may modulate the overall mortality risk. We assessed the associations between the clinical and laboratory characteristics of patients with HCLD with 90-day mortality.MethodsA systematic search of the medical records at our institution over a 10-year period was performed to retrospectively identify subjects with HCLD during inpatient admission. Univariate and multivariable regression analyses were performed to detect the risk factors for all-cause 90-day mortality.ResultsThirty-eight subjects with HCLD were identified using stringent inclusion and exclusion criteria to exclude individuals with other secondary causes of hypercalcemia. A total of 35 subjects had 90-day vital status available, which revealed 40% mortality. The model for end-stage liver disease sodium score and duration of inpatient hypercalcemia were positively associated with mortality with respective odds ratios of 1.23 (95% CI, 1.06-3.23) and 1.24 (95% CI, 1.04-1.49) in a univariate regression model and 1.30 (95% CI, 1.04-1.62) and 1.33 (95% CI, 1.04-1.71) in a multivariable regression model. The admission and peak serum calcium levels were not associated with mortality. Only 6 subjects received bisphosphonates or calcitonin during their admission, limiting our ability to assess the impact of treatment on outcomes.ConclusionIn patients admitted to the hospital with HCLD, the duration of hypercalcemia was positively associated with 90-day mortality, providing a potential interventional target to reduce mortality in this high-risk population. Studies to validate the utility of treating hypercalcemia are required.     

Euthyroid Sick Syndrome as a Prognostic Indicator of COVID-19 Pulmonary Involvement,Associated With Poorer Disease Prognosis and Increased Mortality

ObjectiveThe prevalence of euthyroid sick syndrome (ESS) and its association with the prognosis of COVID-19 and mortality in patients with lung involvement in COVID-19 have not yet been elucidated.MethodsClinical and laboratory data of patients with COVID-19 with or without ESS were collected retrospectively and analyzed on admission. All subjects were admitted to the Department of Internal Diseases and Clinical Pharmacology at Bieganski Hospital between December 2020 and April 2021.ResultsIn total, 310 medical records of patients with COVID-19 were analyzed retrospectively. Among 215 enrolled patients, 82 cases of ESS were diagnosed. The patients with ESS had higher pro-inflammatory factor levels, longer hospitalizations, and a higher risk of requiring high-flow nasal oxygen therapy or intubation than the patients without ESS. The Kaplan-Meier curve indicated that the patients with ESS had a lower probability of survival when computed tomography showed ≤50% parenchymal involvement compared with that in patients without ESS. However, no differences in mortality were noted in those with more than 50% parenchymal involvement. The survival curve showed that ESS was associated with a higher risk of mortality during hospitalization.ConclusionESS is closely associated with a poor prognosis, including longer hospitalizations, more frequent intubation, transfer to the intensive care unit, and a higher mortality rate in patients with COVID-19. ESS is a potential prognostic predictor of survival, regardless of lung involvement in COVID-19.     

Anemia in Patients With Diabetes and Prediabetes With Normal Kidney Function: Prevalence and Clinical Outcomes

ObjectiveAnemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.MethodsThis retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.ResultsA total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567).ConclusionThis study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.     

Quality of Life in Patients With Asymptomatic Primary Hyperparathyroidism After Parathyroidectomy: A 3-Year Longitudinal Study

ObjectiveImpaired quality of life (QoL) is considered as a nonclassical manifestation of primary hyperparathyroidism (PHPT). This study aimed to detect and compare changes in the QoL of patients with asymptomatic PHPT who had successful curative parathyroidectomy (PTX) 3 months and 3 years after the procedure.MethodsPatients with diagnosed PHPT were eligible for the study. There were 2 groups: the PTX group, with patients who underwent PTX, and the non-PTX group, with patients who were treated conservatively. QoL was assessed using Pasieka’s Parathyroid Assessment of Symptoms Questionnaire (PAS-Q) at baseline, 3 months, and 3 years.ResultsThirty-eight patients were included in the study: 18 in the PTX group and 20 in the non-PTX group. In the PTX group, the mean PAS-Q total score before PTX was 518, which was reduced significantly at the 3-month (P = .003) and 3-year assessments (P = .001). However, in the non-PTX group, the mean PAS-Q total score was 326 at baseline and increased continuously for 3 years (P = .019). At the 3-year evaluation, the mean total score was significantly higher compared to that of the PTX group (P = .021). Finally, there was a positive correlation between total serum calcium and PAS-Q score in the non-PTX group (r = 0.524, P = .018).ConclusionQoL of patients with PHPT improved significantly compared to that in conservative surveillance as early as 3 months after successful, curative PTX, and remained improved for 3 years. This finding strengthens, even more, the hypothesis that PTX contributes to better QoL, suggesting that the derangement of QoL may be considered as an individual indication for surgery.     

A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease

ObjectiveNonalcoholic fatty liver disease (NAFLD) affects much of the worldwide population and poses a significant burden to the global healthcare. The rising numbers of individuals with NAFLD and instances of mortality point toward the importance of understanding the association causes of mortality in NAFLD. This meta-analysis aimed to seek the associations of NAFLD with all-cause, cardiovascular disease (CVD)-related, liver-related, and cancer-related mortality.MethodsMEDLINE and Embase were searched for articles relating to causes of mortality between NAFLD and non-NAFLD. The DerSimonian and Laird random-effects model was used to analyze adjusted hazard ratios (HR), and a sensitivity analysis was conducted to reduce heterogeneity through a graphical display of study heterogeneity.ResultsFifteen studies involving 10 286 490 patients were included. Individuals with NAFLD exhibited an increased risk of all-cause mortality (HR, 1.32; 95% CI, 1.09-1.59; P < .01; I² = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I² = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I² = 95.00%). However, no significant association was found between liver-related mortality and NAFLD (HR, 3.58; 95% CI, 0.69-18.46; P =.13; I² = 96.00%). The sensitivity analysis conducted with graphic display of heterogeneity and only population-based studies found similar results.ConclusionNAFLD was associated with an increased risk of all-cause, CVD-related, and cancer-related mortality but not liver-related mortality. The finding is likely because of low fibrosis prevalence in the community. However, the significant burden in other causes of mortality beyond the liver points to a need for multidisciplinary efforts to reduce the mortality risks.     

Effect of Steroid Replacement on Long-Term Kidney Function in Patients With Adrenal Insufficiency

ObjectiveThe prevalence of adrenal insufficiency (AI) is increasing with an increase in the elderly population. Steroid replacement therapy (SRT) is often required in patients with AI because of acute symptoms and complications. The long-term effects of SRT on kidney function have not been well elucidated.MethodsOverall, 788 patients diagnosed with AI between 2010 and 2015 at Yonsei University Health System were retrospectively evaluated. SRT was defined when an equivalent dose of ≥5 mg/d of hydrocortisone was initiated within 30 days of AI diagnosis and maintained for >30 days. Those not included in the SRT group were identified as the no-SRT group. The primary outcome was 40% reduction in the estimated glomerular filtration rate compared with baseline sustained for ≥30 days or end-stage kidney disease development.ResultsThe mean age of was 63.1 ± 15.4 years, and 43.0% were men. The SRT group comprised 387 patients. During a median follow-up duration of 4.1 years, the primary outcome occurred in 118 (15.0%) patients. The outcome incidence rate was higher in the SRT group (4.61/100 patient-years) than in the no-SRT group (2.76/100 patient-years). When the subdistribution hazard ratio for kidney outcome was assessed with death as a competing risk, the risk was 67% higher in the SRT group than in the no-SRT group (subdistribution hazard ratio, 1.67; 95% confidence interval, 1.16-2.45; P = .006). This association was maintained with inverse probability of treatment weighting and adjustment for confounding variables.ConclusionKidney function decline was more prominent in patients with AI who received SRT. Further prospective evaluations are needed to confirm these findings.     

Treatment With 25-Hydroxyvitamin D3 (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter,Randomized, Placebo-Controlled,Double-Blinded Clinical Trial

ObjectiveThe goal of this randomized, double-blinded, placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D₃ (25(OH)D₃) in improving vitamin D status in vitamin D–deficient/vitamin D–insufficient patients infected with the SARS-CoV-2 (COVID-19) virus.MethodsThis is a multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants were recruited from 3 hospitals that are affiliated to [Institution Blinded for Review] and [Institution Blinded for Review].ResultsA total 106 hospitalized patients who had a circulating 25(OH)D₃ concentration of <30 ng/mL were enrolled in this study. Within 30 and 60 days, 76.4% (26 of 34) and 100% (24 of 24) of the patients who received 25(OH)D₃ had a sufficient circulating 25(OH)D₃ concentration, whereas ≤12.5% of the patients in the placebo group had a sufficient circulating 25(OH)D₃ concentration during the 2-month follow-up.We observed an overall lower trend for hospitalization, intensive care unit duration, need for ventilator assistance, and mortality in the 25(OH)D₃ group compared with that in the placebo group, but differences were not statistically significant. Treatment with oral 25(OH)D₃ was associated with a significant increase in the lymphocyte percentage and decrease in the neutrophil-to-lymphocyte ratio in the patients. The lower neutrophil-to-lymphocyte ratio was significantly associated with reduced intensive care unit admission days and mortality.ConclusionOur analysis indicated that oral 25(OH)D₃ was able to correct vitamin D deficiency/insufficiency in patients with COVID-19 that resulted in improved immune function by increasing blood lymphocyte percentage. Randomized controlled trials with a larger sample size and higher dose of 25(OH)D₃ may be needed to confirm the potential effect of 25(OH)D₃ on reducing clinical outcomes in patients with COVID-19.     

Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19

ObjectiveTo determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patientsMethodsWe performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality.ResultsAmong the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index <30 kg/m², vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95% CI, 0.04-0.84). No significant association was found in the subgroups of patients aged <65 years or with body mass index ≥30 kg/m².ConclusionWe revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.     

Thyroid Feedback Quantile-Based Index Is Associated With Blood Pressure and Other Hemodynamic Measures: A Cross-sectional Study

ObjectivePrevious studies have reported inconsistent relationships between thyroid function and blood pressure (BP) levels. We aimed to explore the associations between thyroid hormone sensitivity and BP parameters.MethodsThis retrospective study included 6272 participants who underwent a health examination at the First Hospital of China Medical University between January 2017 and December 2018. The Thyroid Feedback Quantile-based Index (TFQI), Parametric TFQI, thyroid-stimulating hormone index, and thyrotroph thyroxine resistance index were calculated to reflect thyroid hormone sensitivity. Mean arterial pressure, pulse pressure, and rate-pressure product were used to indirectly represent arterial stiffness.ResultsThe TFQI was positively associated with systolic BP (β = 3.22), diastolic BP (β =2.32), and mean arterial pressure (β = 2.62) (P < .001, for all). Analyses of the Parametric TFQI, thyroid-stimulating hormone index, and thyrotroph thyroxine resistance index yielded similar results. The TFQI was positively related to pulse pressure and rate-pressure product. With a 1 SD increase in the TFQI, the adjusted odds ratio for hypertension was 1.11 (95% CI 1.04-1.18). When comparing the fourth quartile of the TFQI with the first, the odds ratio for hypertension was 1.27 (95% CI 1.07-1.51, P_{for trend} = .006). These relationships remained significant when stratified by age, sex, and body mass index. Similar results were observed in a euthyroid or normotensive population.ConclusionThe TFQI was positively associated with BP and markers of arterial stiffness. Impaired thyroid hormone sensitivity was related to increased risk for hypertension.     

Serum Selenium Levels in Patients With Graves Disease With or Without Thyroid Ophthalmopathy

BackgroundGraves disease is one of the most common autoimmune thyroid diseases. Thyroid has the highest concentration of selenium (Se) in the body. Se plays a crucial role in the functioning of some thyroid enzymes; however, there are controversial results regarding the administration of serum Se levels in patients with Graves disease.MethodsIn this study, patients with Graves disease with orbitopathy (GO group) or without orbitopathy (GD group) were recruited. Healthy individuals without a history of any disease were enrolled as the control group. Serum Se and thyroid hormone levels, including T3, T4, and thyroid-stimulating hormone (TSH), were measured using atomic absorption and radioimmunoassay techniques, respectively.ResultsIn this cross-sectional study, 60 and 56 patients and 58 healthy subjects were included in the GO, GD, and control groups. Serum Se levels in the GO, GD, and control groups were 94.53 ± 25.36 μg/dL, 96.82 ± 30.3 μg/dL, and 102.55 ± 16.53 μg/dL, respectively (P = .193). There was a reverse association between the serum Se level and thyroid hormones, including T3, T4, and TSH, in the GO group. However, serum Se levels exhibited a significant reverse association with T4 and TSH hormones but not with T3 in the GD group.ConclusionOur results showed no significant differences in the serum Se levels in the GO and GD groups compared with that in the control group. In addition, we did not detect any significant difference in the serum Se levels between the GO and GD groups.     

Imaging Mass Spectrometry Reveals Alterations in N-Linked Glycosylation That Are Associated With Histopathological Changes in Nonalcoholic Steatohepatitis in Mouse and Human

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD) and is characterized by inflammation, hepatocyte injury, and fibrosis. Further, NASH is a risk factor for cirrhosis and hepatocellular carcinoma. Previous research demonstrated that serum N-glycan profiles can be altered in NASH patients. Here, we hypothesized that these N-glycan modifications may be associated with specific liver damage in NAFLD and NASH. To investigate the N-glycome profile in tissue, imaging mass spectrometry was used for a qualitative and quantitative in situ N-linked glycan analysis of mouse and human NAFLD/NASH tissue. A murine model was used to induce NAFLD and NASH through ad libitum feeding with either a high-fat diet or a Western diet, respectively. Mice fed a high-fat diet or Western diet developed inflammation, steatosis, and fibrosis, consistent with NAFLD/NASH phenotypes. Induction of NAFLD/NASH for 18 months using high caloric diets resulted in increased expression of mannose, complex/fucosylated, and hybrid N-glycan structures compared to control mouse livers. To validate the animal results, liver biopsy specimens from 51 human NAFLD/NASH patients representing the full range of NASH Clinical Research Network fibrosis stages were analyzed. Importantly, the same glycan alterations observed in mouse models were observed in human NASH biopsies and correlated with the degree of fibrosis. In addition, spatial glycan alterations were localized specifically to histopathological changes in tissue like fibrotic and fatty areas. We demonstrate that the use of standard staining’s combined with imaging mass spectrometry provide a full profile of the origin of N-glycan modifications within the tissue. These results indicate that the spatial distribution of abundances of released N-glycans correlate with regions of tissue steatosis associated with NAFLD/NASH.     

Metabolic Associated Fatty Liver Disease Increases the Risk of Systemic Complications and Mortality. A Meta-Analysis and Systematic Review of 12 620 736 Individuals

ObjectiveThe recent introduction of the term metabolic associated fatty liver disease (MAFLD) sought to reclassify nonalcoholic fatty liver disease (NAFLD). MAFLD is thought to improve the encapsulation of metabolic dysregulation. However, recent evidence has found significant differences between MAFLD and NAFLD, and prevailing knowledge has largely arisen from studies on NAFLD. Hence, we conducted a meta-analysis and systematic review of the outcomes associated with MAFLD.MethodsMEDLINE and Embase databases were searched for articles relating to outcomes in MAFLD. Analysis was conducted in random effects with hazard ratios (HRs) to account for longitudinal risk assessment of mortality and systemic complications.ResultsA total of 554 articles were identified, of which 17 articles were included. MAFLD resulted in an increase in the overall mortality (HR, 1.24; confidence interval [CI], 1.13-1.34), cancer-related mortality (HR, 1.27; CI, 1.01-1.54), and cardiovascular disease mortality (HR, 1.28, 1.03-1.53; P = .04) compared with non-MAFLD. MAFLD also increases the risk of cardiovascular events (HR, 1.49; CI, 1.34-1.64; P < .01), stroke (HR, 1.55; CI, 1.37-1.73; P < .01), and chronic kidney disease (HR, 1.53; CI, 1.38-1.68). The presence of MAFLD was also associated with an increased risk of heart failure, obstructive sleep apnea, and malignancy.ConclusionMAFLD can significantly elevate the risk of systemic diseases and mortality. The care of MAFLD thus requires interdisciplinary collaboration, and future clinical trials conducted on MAFLD should aim to reduce the incidence of end-organ damage aside from improving liver histology.     

New Insights on Effects of Glucocorticoids in Patients With SARS-CoV-2 Infection

ObjectiveSince January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients.MethodsTo review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury.ResultsIn our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs.ConclusionFor clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs.     

The Added Value of Second-Look Ultrasound in Patients With Primary Hyperparathyroidism With Discordant or Negative Previous Imaging Findings

ObjectiveThe preoperative localization for patients with primary hyperparathyroidism with negative or discordant previous imaging results has always been a difficult problem to be solved in clinical practice. Second-look ultrasound (US) is a viable but underestimated method. This study aimed to assess the added value of second-look US and explore the attributing factors.MethodsAmong 711 surgically confirmed patients with primary hyperparathyroidism, 63 patients with negative or discordant first-time US and ^99mTc-MIBI imaging results were retrospectively studied. All 63 patients underwent second-look US, and the results were compared with intraoperative findings and histopathologic diagnosis. The diagnostic value of second-look US was calculated, and the reasons for changed second-look US results were analyzed.ResultsSixty-three parathyroid lesions were found in 63 patients. The sensitivity, positive predictive value, and accuracy of second-look US were 92.1%, 95.1%, and 88.1%, respectively. Comparing the results of first-time and second-look US, we found that 54.0% of the patients got benefits from second-look US because 34 patients with negative results in the first-time US revealed localization with second-look US. Second-look US was more likely to produce changes in results for lesions with a lower location (OR, 3.23; 95% CI, 1.11-9.43, P < .05) and larger length-to-thickness ratio (3.0 vs 2.4, P < .05).ConclusionSecond-look US is a promising method to determine preoperative localization in patients with negative or discordant results of previous imaging findings. Lesions with elongated shape and lower location are more expected to be detected in second-look US when missed at the first time.     

Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?

ObjectivePost-acute sequelae of coronavirus disease 2019 (COVID-19) or long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC.MethodsWe included consecutive adults without a known thyroid disorder who were admitted to a major COVID-19 center for confirmed COVID-19 from July to December 2020. Thyroid function tests and antithyroid antibodies were measured for all patients on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up.ResultsIn total, 204 patients (median age, 55.0 years; 95 men [46.6%]) were reassessed at a median of 89 days (interquartile range, 69-99) after acute COVID-19. Of the 204 patients, 41 (20.1%) had LC. Female sex (adjusted odds ratio, 2.48; P = .018) and severe acute respiratory syndrome coronavirus 2 polymerase chain reaction cycle threshold value of <25 on admission (adjusted odds ratio, 2.84; P = .012) independently predicted the occurrence of LC. Upon follow-up, most abnormal thyroid function tests in acute COVID-19 resolved, and incident thyroid dysfunction was rare. Nonetheless, we observed incident antithyroid peroxidase (anti-TPO) positivity. Although baseline or follow-up thyroid function tests were not associated with the occurrence of LC, among 172 patients with symptomatic acute COVID-19, symptom resolution was more likely in those with positive anti-TPO upon follow-up (P = .043).ConclusionLC is common among COVID-19 survivors, with females and those with higher viral load in acute COVID-19 particularly being vulnerable. The observation of incident anti-TPO positivity warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in LC remains to be elucidated.     

Echocardiographic Findings in Patients With Normocalcemic Primary Hyperparathyroidism Compared With Findings in Hypercalcemic Primary Hyperparathyroid Patients and Control Subjects

ObjectiveThere are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls.MethodsSeventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation.ResultsPatients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction).ConclusionIn a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.