A retrospective cohort of tumor-induced osteomalacia and case series of malignant disease.

OBJECTIVE: We aimed to describe the clinical characteristics of a large cohort of patients diagnosed with tumor-induced osteomalacia (TIO), with a focus on patients with non-localizing and malignant TIO. METHODS: This is a retrospective cohort of TIO patients in an academic medical center, diagnosed between January 1998 to May 2023. We described their demographics, biochemistries, tumor features, localization, treatment and complications. RESULTS: Of 68 patients diagnosed with TIO, 49 (72%) were localizing and 5 (7.4%) were malignant. Of 50 patients who attempted localizing procedures, 29 (58%) achieved cure. 20 (40%) had persistent disease due to wrong tumor targeted, or refractory or recurrent tumors, despite up to 6 procedural attempts. There was no difference in demographics, phosphorus or baseline fibroblast growth factor-23 (FGF23) levels between localizing versus non-localizing groups, and malignant versus non-malignant groups. Lower extremity was the commonest site of localization (37%), with 47% in bone and 53% in soft tissue. 60% of malignant cases were located in the trunk. Tumor size correlated with peak FGF23 (R=0.566, p<0.001) but was not associated with malignancy risk (p=0.479). A cut-off FGF23 of >20 times upper limit of normal in the presence of normal renal function (p=0.025), and recurrence after initial cure (p=0.013) were factors significantly associated with malignancy. The non-localizing group had lower survival than localizing group (p=0.0097). CONCLUSIONS: TIO is a condition with significant morbidity. Very high FGF23 level and disease recurrence are associated with malignant disease. Reasons behind the observation of higher mortality in non-localizing TIO should be further explored.

Diabetes predicts severity of COVID-19 infection in a retrospective cohort: A mediatory role of the inflammatory biomarker C-reactive protein.

Diabetes is a risk factor for developing severe COVID-19, but the pathogenesis remains unclear. We investigated if the association of diabetes and COVID-19 severity may be mediated by inflammation. We also hypothesized that this increased risk may extend to prediabetes. Hospitalized patients in Singapore with COVID-19 were subdivided into three groups in a retrospective cohort: normoglycemia (HbA1c: ≤5.6%), prediabetes (HbA1c: 5.7%-6.4%) and diabetes (HbA1c: ≥6.5%). The primary outcome of severe COVID-19 was defined by respiratory rate ≥30, SpO2 ≤93% or intensive care unit admission. The association between clinical factors on severe COVID-19 outcome was analyzed by cox regression. Adjusted mediation analysis of C-reactive protein (CRP) on the relationship between diabetes and severe COVID-19 was performed. Of 1042 hospitalized patients, mean age 39 ± 11 years, 13% had diabetes, 9% prediabetes and 78% normoglycemia. Severe COVID-19 occurred in 4.9% of subjects. Compared to normoglycemia, diabetes was significantly associated with severe COVID-19 on both univariate (hazard ratio [HR]: 9.94; 95% confidence interval [CI]: 5.54-17.84; p < .001) and multivariate analysis (HR: 3.99; 95% CI: 1.92-8.31; p < .001), while prediabetes was not a risk factor (HR: 0.94; 95% CI: 0.22-4.03; p = .929). CRP, a biomarker of inflammation, mediated 32.7% of the total association between diabetes and severe COVID-19 outcome. In conclusion, CRP is a partial mediator of the association between diabetes and severe COVID-19 infection, confirming that inflammation is important in the pathogenesis of severe COVID-19 in diabetes.

Viral arthralgia a new manifestation of COVID-19 infection? A cohort study of COVID-19-associated musculoskeletal symptoms.

OBJECTIVES: Musculoskeletal symptoms are often unrecognised as a prominent feature of COVID-19 infection. This study hypothesised that viral arthralgia is an uncommon but distinct manifestation of COVID-19 infection. In addition, it aimed to characterise the other musculoskeletal presentations of COVID-19 infection and study their prognostic implications. METHODS: Patients hospitalised with COVID-19 infection were divided into two groups: those with and without musculoskeletal symptoms. Those with musculoskeletal symptoms were subdivided according to four patterns of musculoskeletal involvement: myalgia, arthralgia, backache and generalised body ache. Using binary regression logistic analysis, the risk of developing a viral pneumonia in patients with and without musculoskeletal complaints was compared. RESULTS: Of 294 hospitalised patients with COVID-19, 88 (30%) reported musculoskeletal complaints. Among these 88 patients, 37.5% had myalgia, 5.7% arthralgia, 6.8% new-onset backache and 50% generalised body ache. The presence of musculoskeletal complaints was not associated with the risk of developing viral pneumonia (6.8% vs. 9.7%, OR 0.68, 95% CI 0.26-1.76, p = 0.426). COVID-19 arthralgia was often more severe and had variable onset, while generalised body ache and myalgia were milder and coincided with the occurrence of fever or respiratory symptoms. CONCLUSION: Viral arthralgia is a novel clinical manifestation of COVID-19, and untypical of a viral prodrome or a reactive arthropathy. While musculoskeletal symptoms were not associated with developing a pneumonia, to avoid missing a diagnosis of COVID-19, clinicians should be aware of its variable onset, particularly when respiratory symptoms are absent at the time of presentation.

Obesity is Associated with Poor Covid-19 Outcomes: A Systematic Review and Meta-Analysis.

Our aim was to assess the association between obesity and the risk of unfavourable outcomes (composite of severe disease and mortality) in inpatients with COVID-19. We conducted a systematic search of databases between December 2019 and 28th June 2020. Studies were included if they reported or allowed estimation of an odds ratio (OR) for unfavourable outcome in obese compared to non-obese patients hospitalised for COVID-19. Twenty cohort studies of 28 355 hospitalised patients with COVID-19 infection were included. Meta-analysis estimated a pooled OR of 2.02 (1.41-2.89, p<0.001) for an unfavourable outcome in obese versus non-obese patients when adjusted for age, sex and co-morbidities. When unadjusted for confounders, the OR for unfavourable outcomes was 1.25 (CI 1.07-1.45, p=0.005). An increased adjusted OR was also seen for death (OR 1.51; CI 1.13-2.21, p=0.006) and severe illness (OR 2.26; CI 1.47-3.48, p<0.001). Compared to a normal BMI, the risk of an unfavourable outcome was increased even in overweight patients, with severe obesity having an escalated risk.Obesity is independently associated with an unfavourable outcome of COVID-19 illness, with obese patients having twice the risk of a composite outcome of severe disease or mortality, and a 50% increased risk of death.

Effects of external counter-pulsation on endothelial function assessed by peripheral artery tonometry, levels of glycaemia and metabolic markers in individuals with type 2 diabetes mellitus.

BACKGROUND AND AIMS: External counter-pulsation (ECP) generates sheer stress thereby improving endothelial function and anginal symptoms in coronary artery disease. Endothelial dysfunction is also involved in the pathogenesis of T2DM. The aim of this pilot study was to investigate the use of ECP at different doses in improving endothelial function and glycaemic markers in T2DM. METHODS: This prospective study involved 46 subjects with T2DM randomly assigned to receive 35 sessions of ECP at different regimens (0.5 h versus 1 h) and duration (7 versus 12 weeks). Endothelial function was evaluated by reactive hyperaemia index (RHI) via peripheral arterial tonometry at the start, midpoint and end of study. Other secondary outcomes included fasting glucose, HOMA-IR, HbA1c, blood pressure, lipid profile, weight and vibration sense. RESULTS: There was no change in RHI across all 3 regimens of ECP individually or collectively at the end of the study (ΔRHI +0.01%, p = 0.458). Glycaemic markers also remained unchanged at endpoint. Subgroup analysis showed an improvement in RHI (ΔRHI +20.6%, p = 0.0178) in subjects with more severe endothelial dysfunction at baseline. CONCLUSION: ECP did not show a beneficial effect on endothelial function or glycemic control in this South-East Asian population with T2DM at any of the three regimens. This may partly be explained by less severe endothelial dysfunction and less insulin resistance in our population at baseline.

Are Adequate Vitamin D Levels Helpful in Fighting COVID-19? A Look at the Evidence.

COVID-19 is a global pandemic with high mortality in vulnerable groups. Given the current lack of definitive treatment or vaccine that significantly reduces mortality rate, governments, researchers and healthcare providers are racing to find possible solutions to the crisis. Vitamin D and its analogues have been previously studied for their non-skeletal benefits. In particular, questions regarding their role in the modulation of immunity have re-surfaced, in view of possible epidemiological links observed between COVID-19 and vitamin D levels in selected populations. In this review, we highlight potential mechanisms and summarise the evidence for and against the potential role of vitamin D supplementation in our fight against COVID-19.

Outcomes of heart failure with preserved ejection fraction in a Southeast Asian cohort.

BACKGROUND: Heart failure with preserved ejection fraction (HF-PEF) has been shown to be of better or equivalent prognosis than heart failure with reduced ejection fraction (HF-REF). We aimed to characterize and study the outcome of HF-PEF in a multiethnic South East Asian context. METHODS: This is a single-centre retrospective analysis of 312 patients admitted with decompensated heart failure over 1 year from January to December 2009. We evaluated clinical characteristics of patients according to left ventricular ejection fraction at least 50 or less than 50%. Outcomes as defined by 1-year mortality and 90-day re-hospitalization rates for heart failure were compared between the two groups in an in-patient setting. RESULTS: The median age was 68 years and median length of hospitalization was 4 days. Around 21.8% had HF-PEF. Patients with preserved ejection fraction were more often older, female, hypertensive, with atrial fibrillation, had no coronary artery disease and had never smoked before. They were less often prescribed antiplatelets, angiotensin-converting enzyme inhibitor/angiotensin-II receptor blocker, aldosterone-receptor antagonists, digoxin and loop diuretics. After 1 year, mortality was 5.9% in patients with HF-PEF and 11.3% in those with HF-REF, but the difference was nonsignificant (P = 0.195). There was also no difference in 90-day rehospitalization rates between the groups (16.2 vs. 17.6%, respectively, P = 0.780). Poor prognostic factors for the cohort of heart failure patients included increased age, diabetes and renal impairment, but not left ventricular ejection fraction. CONCLUSION: HF-PEF is associated with distinct risk factors from HF-REF, but has a similar morbidity and mortality to HF-REF.