Skeletal impact of parathyroidectomy on patients with primary hyperparathyroidism: a Systematic review and Meta-analysis.

CONTEXT: Parathyroidectomy is recommended for curing primary hyperparathyroidism (PHPT), although uncertainty remains regarding the extent of fracture risk reduction following surgery. OBJECTIVE: To compare fracture risk and bone mineral density (BMD) changes in patients with PHPT undergoing parathyroidectomy (PTX) versus observation (OBS). DATA SOURCES: We systematically searched PubMed, Embase, and the Cochrane Library until September 2022, including randomized controlled trials (RCTs) and cohort studies, and reviewed citations from previous reviews. STUDY SELECTION: Among 1,260 initial records, 48 eligible articles from 35 studies (5 RCTs; 30 cohorts) included PHPT patients receiving PTX or OBS interventions with reported fracture events at any site, including the hip, spine, or forearm, and/or BMD changes at each location. DATA EXTRACTION: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines by two independent reviewers. DATA SYNTHESIS: In 238,188 PHPT patients (PTX: 73,778 vs. OBS: 164,410), parathyroidectomy significantly reduced fractures at any site (RR, 0.80; 95%CI, 0.74-0.86) compared to observation. In 237,217 patients (PTX: 73,458 vs. OBS: 163,759), the risk of hip fractures decreased (RR, 0.63; 95%CI, 0.52-0.76). No reduction in forearm and vertebral fractures was observed in 3,574 and 3,795 patients, respectively. The annual percentage BMD changes from baseline were higher in the PTX group: femoral neck, 1.91% (95%CI, 1.14-2.68); hip, 1.75% (95%CI, 0.58-2.92); radius, 1.75% (95%CI, 0.31-3.18); spine, 2.13% (95%CI, 1.16-3.10). CONCLUSIONS: Parathyroidectomy significantly reduced overall and hip fracture risks in PHPT patients. Despite minimal BMD increase, the substantial decrease in fracture risk suggests additional benefits of PTX beyond mineral content enhancement.

Protection of inactivated vaccine against SARS-CoV-2 infections in patients with comorbidities: a prospective cohort study.

Protection against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection of inactivated vaccines is not well characterized in people with comorbidities, who are at high risk of severe infection. We compared the risk of SARS-CoV-2 infection after complete vaccination with Sinopharm/BBIBP in people with comorbidities (e.g., autoimmune diseases, cardiovascular disease, chronic lung disease, and diabetes) with healthy individuals using a Cox-proportional hazard model. In July-September 2021, a total of 10 548 people (comorbidities, 2143; healthy, 8405) receiving the complete primary series of vaccination with Sinopharm/BBIBP in Bangkok, Thailand were prospectively followed for SARS-CoV-2 infection through text messaging and telephone interviewing for 6 months. A total of 295 infections from 284 participants were found. HRs (95% CI) of individuals with any comorbidities did not increase (unadjusted, 1.02 (0.77-1.36), P = 0.89; adjusted, 1.04 (0.78-1.38), P = 0.81). HRs significantly increased in the subgroup of autoimmune diseases (unadjusted, 2.64 (1.09-6.38), P = 0.032; adjusted, 4.45 (1.83-10.83), P = 0.001) but not in cardiovascular disease, chronic lung disease, or diabetes. The protection against SARS-CoV-2 infection of the Sinopharm vaccine was similar in participants with any comorbidities vs. healthy individuals. However, the protection appeared lower in the subgroup of autoimmune diseases, which may reflect suboptimal immune responses among these people.

Mortality Risk in Patients With Adrenal Insufficiency Using Prednisolone or Hydrocortisone: A Retrospective Cohort Study.

CONTEXT: Prednisolone has been recommended rather than hydrocortisone for glucocorticoid replacement in adrenal insufficiency due its longer duration of action and lower cost. OBJECTIVE: To determine mortality rates with prednisolone versus hydrocortisone. METHODS: In this observational study, we used data extracted from a UK primary care database (Clinical Practice Research Datalink) to measure the relative mortality of patients with primary and secondary adrenal insufficiency, who were treated with either prednisolone or hydrocortisone, and control individuals who were individually matched for age, sex, period, and place of follow-up. RESULTS: As expected, mortality in adrenal insufficiency irrespective of cause was increased, based on 5478 patients (4228 on hydrocortisone; 1250 on prednisolone) and 54 314 controls (41 934 and 12 380, respectively). Overall, the adjusted hazard ratio (HR) was similar with the 2 treatments (prednisolone, 1.76 [95% CI, 1.54-2.01] vs hydrocortisone 1.69 [1.57-1.82]; P = 0.65). This was also the case for secondary adrenal insufficiency. In primary disease (1405 on hydrocortisone vs 137 on prednisolone; 13 965 and 1347 controls, respectively), prednisolone users were older, more likely to have another autoimmune disease and malignancy, and less likely to have mineralocorticoid replacement. Nevertheless, after adjustment, the HR for prednisolone-treated patients remained higher than for those taking hydrocortisone (2.92 [2.19-3.91] vs 1.90 [1.66-2.16]; P = 0.0020). CONCLUSION: In primary but not in secondary adrenal insufficiency, mortality was higher with prednisolone. The study was large, but the number of prednisolone-treated patients was small, and they had greater risk factors. Nonetheless, the increased mortality associated with prednisolone persisted despite statistical adjustment. Further evidence is needed regarding the long-term safety of prednisolone as routine replacement.

Cardiovascular Disease in Patients With Primary and Secondary Adrenal Insufficiency and the Role of Comorbidities.

CONTEXT: Mortality studies have established that cardiovascular disease is the leading cause of death in patients with adrenal insufficiency and the risk is greater than that observed in individually matched controls. OBJECTIVE: Here we have performed a detailed analysis of cardiovascular morbidity and mortality, taking account of the role of comorbidities. METHODS: We performed a retrospective cohort study using the Clinical Practice Research Datalink (CPRD), a UK general practitioner database. The participant population comprised 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) compared with 67 564 individually matched controls, with and without adjustment for comorbidities (diabetes, hypertension, dyslipidemia, previous cardiovascular disease, and smoking). The main outcome measures were composite cardiovascular events recorded in the CPRD and cardiovascular mortality in participants with linked national mortality data. RESULTS: Hazard ratios (95% CI) for composite cardiovascular events in patients with adrenal insufficiency of any cause were 1.28 (1.20-1.36, unadjusted) and 1.07 (1.01-1.14, adjusted). Increased cerebrovascular events in patients with secondary adrenal insufficiency accounted for most of the increased hazard (1.53 [1.34-1.74, adjusted]) and were associated with cranial irradiation therapy. Cardiovascular mortality data were available for 3547 patients and 34 944 controls. The adjusted hazard ratio for ischemic heart disease mortality was 1.86 (1.25-2.78) for primary adrenal insufficiency and 1.39 (1.02-1.89) for secondary. CONCLUSION: Comorbidities largely accounted for the increased cardiovascular events but in secondary adrenal insufficiency, cerebrovascular events were independently increased and associated with irradiation treatment. However, the risk of cardiovascular mortality remained increased even following adjustment for comorbidities in both primary and secondary adrenal insufficiency.

Increased Mortality Risk in Patients With Primary and Secondary Adrenal Insufficiency.

CONTEXT: Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations. OBJECTIVE: To compare mortality risk and causes of death in adrenal insufficiency with an individually matched reference population. METHODS: A retrospective cohort study was done using a UK general practitioner database (CPRD). A total of 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) were compared with 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcomes were all-cause and cause-specific mortality, and hospital admission from adrenal crisis. RESULTS: With follow-up of 40 799 and 406 899 person-years for patients and controls respectively, the hazard ratio (HR [95% CI]) for all-cause mortality was 1.68 [1.58-1.77]. HRs were greater in primary (1.83 [1.66-2.02]) than in secondary (1.52 [1.40-1.64]) disease; primary versus secondary disease (1.16 [1.03-1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15-7.46]). Adrenal crisis contributed to 10% of all deaths. In the first 2 years following diagnosis, the patients' mortality rate and hospitalization from adrenal crisis were higher than in later years. CONCLUSION: Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality.

Clinical Outcomes of Minimized Hydrocortisone Dosage of 100 Mg/Day on Lower Occurrence of Hyperglycemia in Septic Shock Patients.

BACKGROUND: The current international guideline recommended 200 mg/day of hydrocortisone intravenously to treat septic shock. However, a subsequent study on cortisol metabolism actually showed an increase in cortisol level during sepsis. Hence, the smaller hydrocortisone dose of 100 mg/day might be sufficient and reduce steroid-associated complications. We aimed to compare the clinical outcomes of minimized hydrocortisone dose of 100 mg to the currently recommended dose in the treatment of septic shock patients. METHODS: A double-blinded randomized controlled trial included 80 septic shock patients with hemodynamic instability despite fluid and vasopressive therapy. Participants were divided equally into two groups to treat with 100 mg/day or 200 mg/day of hydrocortisone, then stepwise down titrated and discontinued on day 8. The outcome of interest was the hyperglycemic rate. Vital status, time to shock reversal, superinfection and gastrointestinal bleeding rates were also compared. RESULTS: Patients with 100 mg hydrocortisone had significantly lower hyperglycemic rate compared with 200 mg, 63.9% versus 86.5% (the adjusted hazard ratio [HR], 0.08; 95% confidence interval [CI], 0.02-0.41, P = 0.002). Time to shock reversal was shorter in patients with 100 mg hydrocortisone, 2 days vs. 4 days, P = 0.031. The 28-day mortality rate when adjusted for Simplified Acute Physiology Score II showed no significant difference (HR, 0.68; 95% CI, 0.37-1.24, P = 0.209). The reinfection and gastrointestinal bleeding rates were comparable between groups. CONCLUSION: Minimized daily hydrocortisone dosage of 100 mg could lower the occurrence of hyperglycemia without increasing mortality in septic shock, compared with the currently recommended dosage of 200 mg/day.

Clinical inertia causing new or progression of diabetic retinopathy in type 2 diabetes: A retrospective cohort study.

BACKGROUND: Clinical inertia is a failure to intensify treatment according to evidence-based guidelines, and can have both short- and long-term adverse effects for type 2 diabetes (T2D). The aim of the present study was to demonstrate the effects of clinical inertia on glycemic control and diabetes-related complications. METHODS: A retrospective cohort study was conducted at a university-based hospital in Thailand. Medical records were evaluated retrospectively from January 2010 to December 2014. Patients were classified into two groups: clinical inertia and non-inertia. Clinical inertia was defined as failure to initiate insulin within 3 months in patients with HbA1c ≥9 % who were already taking two oral antidiabetic agents. RESULTS: From 1206 records, 98 patients with mean HbA1c of 10.3 % were identified and enrolled in the study. The median follow-up time of these patients was 29.5 months and 68.4 % were classified into the clinical inertia group. The mean (± SD) HbA1c decrement in the clinical inertia and non-inertia groups was 0.82 ± 1.50 % and 3.02 ± 1.80 %, respectively, at 6 months (P < 0.001) and 1.46 ± 1.85 % and 3.04 ± 1.76 %, respectively, at the end of study (P < 0.001). Clinical inertia was associated with a significantly shorter median time to progression of diabetic retinopathy (DR); log rank test, P = 0.02 and a higher incidence of DR progression (10 vs 2.2 cases per 1000 person-months; P = 0.003). The adjusted incidence rate ratio for DR progression in the clinical inertia group was 4.92 (95 % confidence interval 1.11-21.77; P = 0.036). Being treated by general practitioners was the strongest risk factor associated with clinical inertia. CONCLUSIONS: Clinical inertia can cause persistently poor glycemic control and speed up the progression of DR in T2D.

Clinical course of IgG4-related hypophysitis presenting with focal seizure and relapsing lymphocytic hypophysitis.

BACKGROUND: This is the first case report of focal seizure as a manifestation of Immunoglobulin G4 (IgG4)-related hypophysitis. IgG4-related hypophysitis is a novel category of hypophysitis. The clinical presentations, imaging studies and initial pathology studies can mimic lymphocytic hypophysitis. Here we report additional clinical clues in differentiating these two conditions. CASE PRESENTATION: A 43-year-old Thai male presented with focal seizure, headache, and anterior pituitary hypofunction. His MRI study showed typical hypophysitis lesion with abnormal cerebral parenchymal signal intensity at right frontal lobe. The pituitary biopsied was obtained and the patient was initially diagnosed with lymphocytic hypophysitis. Following initial low-dose steroid therapy, his seizure and headache resolved but his anterior pituitary hormones remained deficient. However, during steroid tapering, he developed new onset acute visual loss. Upon rigorous pathologic review, his diagnosis of IgG4-related hypophysitis with suspected CNS involvement was established. He was subsequently treated with high-dose steroid and rapidly regained his sight. CONCLUSION: This case report highlights the important distinguishing features of IgG4-related hypophysitis from lymphocytic hypophysitis. These include the relapsing clinical course of hypophysitis after steroid decrement and concomitant pachymeningitis particularly in middle-aged to elderly Asian male who presented with hypophysitis. With appropriate dosage of steroids, medical treatment is usually sufficient to control the disease and surgical interventions are usually not required.

Apolipoprotein A-V is not a major determinant of triglyceride levels during human sepsis.

PURPOSE: During critical illnesses, alterations in lipid metabolism occur. We examined levels of apolipoprotein A-V, a novel regulator of triglyceride metabolism, during sepsis in humans. METHODS: Seventy-five cases of sepsis and 75 cases of acute illnesses not associated with infection were recruited. Lipids and apolipoprotein A-V levels were measured by enzymatic methods and enzyme-linked immunosorbent assay, respectively, within 24 hours of diagnosis. Fifty healthy controls were also enrolled. RESULTS: During sepsis and acute illnesses, serum total cholesterol and high-density lipoprotein cholesterol levels were significantly lower than those in controls. Serum triglyceride levels, however, were not significantly different. Similarly, serum apolipoprotein A-V levels during sepsis were not significantly different from those during acute illnesses and those in controls (expressed as median [interquartile range]: 149.6 [97.5-257.1] vs 157.9 [98.4-238.2] and 155.9 [91.5-253.8] ng/mL, respectively; P = .98); and they were not correlated with serum triglyceride levels. Low apolipoprotein A-V levels were associated with higher mortality, but the association became nonsignificant after adjusting for high-density lipoprotein cholesterol levels. CONCLUSIONS: During sepsis or acute illnesses, serum apolipoprotein A-V levels were not significantly different from those in controls. Furthermore, apolipoprotein A-V levels were not linearly correlated with triglyceride levels, suggesting that it might not be a major determinant of triglyceride levels during sepsis.

Diabetes Mellitus Treated with Medical Nutritional Therapy and Self Blood Glucose Monitoring: A Randomized Controlled Trial.

OBJECTIVE: To assess the effect of Medical Nutritional Therapy (MNT) combined with self blood glucose monitoring (SBGM) in the clinical outcomes of patients with type 2 diabetes. MATERIAL AND METHOD: A randomized controlled trial was conducted on patients with uncontrolled, not-using insulin type 2 diabetes at Her Royal Highness Princess Maha Chakri Sirindhorn Medical Center Sixty patients were recruited and randomized equally into intervention group (MNT with SBGM) and control group (usual care). The primary endpoint was improvement of hemoglobin A1c (HbA1c) at 12 and 24 weeks. RESULTS: At 12 and 24 weeks the intervention group had significantly improved their glycemic control in comparison to control group (median decrement of HbA1c at 12 weeks 0.72% vs. 0.15%; p < 0.001 and at 24 weeks 0.85% vs. 0.20%; p < 0.001). Oral hypoglycemic agents were reduced or discontinued in 7 patients in the intervention group and 1 patient in control group who achieved HbA1c goal after 24 weeks (p = 0.037). After 24 weeks, body weight was significantly decreased from baseline (2.3 kg, p < 0.001) in the intervention group while only non-significant decrease was observed in control group (0.1 kg, p = 0.632). CONCLUSION: MNT combined with SBGM is an effective non-pharmacological intervention for patients with uncontrolled type 2 diabetes.