A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion. The initial approach is similar in most cases, but a definitive treatment depends on etiology, that is why etiological investigation is mandatory in all cases. The majority of patients are asymptomatic and diagnosed during routine exams; only a small percentage of patients present with severe manifestations which can affect neurological, muscular, gastrointestinal, renal, and cardiovascular systems. Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms. Critically ill patients should receive treatment as soon as diagnosis is made. Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption such as bisphosphonates and, more recently, denosumab, in refractory cases; also, corticosteroids and calcitonin can be used in specific cases. This review aims to provide a clinical update on current concepts of the pathophysiology of calcium homeostasis, epidemiology, screening, clinical presentation, diagnosis, and management of hypercalcemia.

Protein Carbonyl, But Not Malondialdehyde, Is Associated With ICU Mortality in Patients With Septic Shock.

BACKGROUND: The objective of our study was to evaluate the association of serum malondialdehyde (MDA) and protein carbonyl concentration with intensive care unit (ICU) mortality in patients with septic shock. METHODS: We prospectively evaluated 175 patients aged over 18 years with septic shock upon ICU admission. However, 16 patients were excluded. Thus, 159 patients were enrolled in the study. In addition, we evaluated 16 control patients. At the time of the patients' enrollment, demographic information was recorded. Blood samples were taken within the first 24 hours of the patient's admission to determine serum MDA and protein carbonyl concentrations. RESULTS: The mean age was 67.3 ± 15.9 years, 44% were males, and the ICU mortality rate was 67.9%. Median MDA concentration was 1.53 (0.83-2.22) µmol/L, and median protein carbonyl concentration was 24.0 (12.7-32.8) nmol/mL. Patients who died during ICU stay had higher protein carbonyl concentration. However, there was no difference in MDA levels between these patients. Receiver operating characteristic curve analysis showed that higher levels of protein carbonyl were associated with ICU mortality (area under the curve: 0.955; 95% confidence interval [CI]: 0.918-0.992; P < .001) at the cutoff of >22.83 nmol/mL (sensibility: 80.4% and specificity: 98.1%). In the logistic regression models, protein carbonyl concentrations (odds ratio [OR]: 1.424; 95% CI: 1.268-1.600; P < .001), but not MDA concentrations (OR: 1.087; 95% CI: 0.805-1.467; P = .59), were associated with ICU mortality when adjusted for age, gender, and Acute Physiology and Chronic Health Evaluation (APACHE) II score; and when adjusted by APACHE II score, lactate, and urea; protein carbonyl concentrations (OR: 1.394; 95% CI: 1.242-1.564; P < .001); and MDA (OR: 1.054; 95% CI: 0.776-1.432; P = .73). CONCLUSION: In conclusion, protein carbonyl, but not MDA, concentration is associated with ICU mortality in patients with septic shock.

Goldman score, but not Detsky or Lee indices, predicts mortality 6 months after hip fracture.

BACKGROUND: Over the past years, several cardiac risk indices were evaluated and modified, including Goldman, Detsky, and Lee scores. The predictive capacity of these scores in hip fracture patients is lacking. Thus, our objective was to compare the Goldman, Detsky, and Lee scores as predictors of mortality in 6 months after hip fracture. METHODS: We prospectively evaluated 80 consecutive patients with hip fractures, over the age of 65 admitted to an orthopedic ward at Botucatu Medical School. Patient demographic information, Goldman, Detsky and Lee scores were recorded. All patients were followed for 6 months after hip fracture, and mortality was recorded. Multiple logistic regression analyses were performed for mortality prediction. RESULTS: The mortality rate was 23% after a 6-month follow-up period. Patients who died had advanced age and the majority of them were male. They also had lower values of handgrip strength, and higher values of creatinine and urea. In the multiple logistic regression models when adjusted by age, gender, handgrip strength and creatinine, Goldman's score (OR:3.025; 95%CI:1.022-8.953; p:0.046), but not Detsky (OR:2.328; 95%CI:0.422-12.835; p:0.332) and Lee (OR:1.262; 95%CI:0.649-2.454; p:0.494), was associated with mortality 6 months after hip fracture. Each 1 category increase in Goldman score increased the mortality to more than 3-fold. CONCLUSIONS: In conclusion, our data suggest that Goldman score, but not Detsky or Lee indices, predicts mortality associated with hip fracture at up to 6 months post-injury.