Incidence and predictors of hypocalcemia in end-stage renal disease patients on denosumab therapy: A systematic review and metaanalysis

BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notably hypocalcemia,are prevalent in patients with end-stage renal disease(ESRD).AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD.METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.PubMed,Scopus,Cochrane Central,and EMBASE were systematically searched from inception through March 2024.All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted.The primary outcomes of our study were the incidence of mild,severe,and very severe hypocalcemia.Secondary outcomes included serum levels of intact parathyroid hormone,calcium,and phosphate.The results were pooled and analyzed using a random-effects model.RESULTS Seven articles comprising 3240 patients were included in our study.Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia[risk ratio(RR):2.79;95%confidence interval(CI):0.99-7.91;P=0.05;I^(2)=37%]and of very severe hypocalcemia(RR:9.58;95%CI:1.58-57.98;P=0.01;I^(2)=49%).However,an increase in the occurrence of severe hypocalcemia was non-significant(RR:4.23;95%CI:0.47-38.34;P=0.20;I^(2)=96%).Alternatively,denosumab showed a significant decrease in serum intact parathyroid hormone[mean difference(MD):-433.20,95%CI:-775.12 to-91.28,I2=98%,P=0.01],while there was a non-significant decrease in phosphate(MD:-0.47,95%CI:-1.35 to 0.41,I^(2)=88%,P=0.30)and calcium levels(MD:-0.33,95%CI:-0.95 to 0.29,I^(2)=94%,P=0.29).CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.

Glucose control in critical care

Glycemic control among critically-ill patients has been a topic of considerable attention for the past 15 years. An initial focus on the potentially deleterious effects of hyperglycemia led to a series of investigations regarding intensive insulin therapy strategies that targeted tight glycemic control. As knowledge accumulated, the pursuit of tight glycemic control among critically-ill patients came to be seen as counterproductive, and moderate glycemic control came to dominate as the standard practice in intensive care units. In recent years, there has been increased focus on the importance of hypoglycemic episodes, glycemic variability, and premorbid diabetic status as factors that contribute to outcomes among critically-ill patients. This review provides a survey of key studies on glucose control in critical care, and aims to deliver perspective regarding glycemic management among critically-ill patients.

Pulmonary complications of hepatic diseases

Severe chronic liver disease(CLD) may result from portal hypertension, hepatocellular failure or the combination of both. Some of these patients may develop pulmonary complications independent from any pulmonary pathology that they may have. Among them the hepatopulmonary syndrome(HPS), portopulmonary hypertension(PPH) and hepatic hydrothorax(HH) are described in detail in this literature review. HPS is encountered in approximately 15% to 30% of the patients and its presence is associated with increase in mortality and also requires liver transplantation in many cases. PPH has been reported among 4%-8% of the patient with CLD who have undergone liver transplantation. The HH is another entity, which has the prevalence rate of 5% to 6% and is associated in the absence of cardiopulmonary disease. These clinical syndromes occur in similar pathophysiologic environments. Most treatment modalities work as temporizing measures. The ultimate treatment of choice is liver transplant. This clinical review provides basic concepts; pathophysiology and clinical presentation that will allow the clinician to better understand these potentially life-threatening complications. This article will review up-to-date information on the pathophysiology, clinical features and the treatment of the pulmonary complications among liver disease patients.

Diabetes, sleep apnea, obesity and cardiovascular disease: Why not address them together?

Obesity, sleep apnea, diabetes and cardiovascular diseases are some of the most common diseases encountered by the worldwide population, with high social and economic burdens. Significant emphasis has been placed on obtaining blood pressure, body mass index, and placing importance on screening for signs and symptoms pointing towards cardiovascular disease. Symptoms related to sleep, or screening for sleep apnea has been overlooked by cardiac, diabetic, pulmonary and general medicine clinics despite recommendations for screening by several societies. In recent years, there is mounting data where obesity and obstructive sleep apnea sit at the epicenter and its control can lead to improvement and prevention of diabetes and cardiovascular complications. This editorial raises questions as to why obstructive sleep apnea screening should be included as yet another vital sign during patient initial inpatient or outpatient visit.

Hydrocortisone, ascorbic acid and thiamine for sepsis: Is the jury out?

Sepsis and septic shock remain a major cause of morbidity and mortality among patients admitted in the intensive care unit.Diabetes is a major risk factor for the development of sepsis.The global mortality of sepsis remains high,despite significant interventions and guidelines.It has been known for decades that patients with sepsis have reduced levels of antioxidants,most notably vitamin C.Furthermore,experimental data has demonstrated multiple beneficial effects of vitamin C in sepsis.In addition,corticosteroids and thiamine may have synergistic biological effects together with vitamin C.Preliminary data suggests that therapy with hydrocortisone,ascorbic acid and thiamine improves the outcome of patients with sepsis with the potential to save millions of lives.However,this intervention has met with much resistance and has not been widely adopted.Ultimately,we await the final jury verdict on this simple,safe and cheap intervention.

Severe insulin resistance treatment with intravenous chromium in septic shock patient

Insulin resistance has been well documented in critically ill patients.Adequate blood sugar control has been associated with better wound healing,and better outcomes in selected patient populations.Chromium is an essential component of human diet.It is believed to affect changes in glucose uptake.Several studies have shown beneficial effects of oral chromium in diabetic patients with insulin resistance,but role of intravenous chromium infusion has not been completely evaluated.We present a case of extreme insulin resistance in a 62-year-old woman with history of diabetes who suffered a cardiac arrest and respiratory failure,leading to aspiration pneumonia and septic shock requiring greater than 7000 units of insulin over a period of 12 h which was successfully treated with intravenous chromium replacement.

What we learned in the past year in managing our COVID-19 patients in intensive care units?

Coronavirus disease 2019 is a pandemic,was first recognized at Wuhan province,China in December 2019.The disease spread quickly across the globe,spreading stealthily from human to human through both symptomatic and asymptomatic individuals.A multisystem disease which appears to primarily spread via bio aerosols,it has exhibited a wide clinical spectrum involving multiple organ systems with the respiratory system pathology being the prime cause of morbidity and mortality.Initially unleashing a huge destructive trail at Wuhan China,Lombardy Italy and New York City,it has now spread to all parts of the globe and has actively thrived and mutated into new forms.Health care systems and Governments responded initially with panic,with containment measures giving way to mitigation strategies.The global medical and scientific community has come together and responded to this huge challenge.Professional medical societies quickly laid out“expert”guidelines which were conservative in their approach.Many drugs were re formulated and tested quickly with the help of national and international collaborative groups,helping carve out effective treatment strategies and help build a good scientific foundation for evidencebased medicine.Out of the darkness of chaos,we now have an orderly approach to manage this disease both from a public health preventive and therapeutic standpoint.With preventive measures such as masking and social distancing to the development of highly effective and potent vaccines,the public health success of such measures has been tempered by behavioral responses and resource mobilization.From a therapy standpoint,we now have drugs that were promising but now proven ineffective,and those that are effective when given early during viral pathogenesis or later when immune dysregulation has established,and the goal is to help reign in the destructive cascade.It has been a fascinating journey for mankind and our work here recapitulates the evolution of various aspects of critical care and other inpatient practices which continue to evolve.