Hypercalcemia of Malignancy: An Update on Pathogenesis and Management

Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care

High-altitude Pulmonary Hypertension: An Update on Disease Pathogenesis and Management

High-altitude pulmonary hypertension (HAPH) affects individuals residing at altitudes of 2,500 meters and higher. Numerous pathogenic variables play a role in disease inception and progression and include low oxygen concentration in inspired air, vasculopathy, and metabolic abnormalities. Since HAPH affects only some people living at high altitude genetic factors play a significant role in its pathogenesis. The clinical presentation of HAPH is nonspecific and includes fatigue, shortness of breath, cognitive deficits, cough, and in advanced cases hepatosplenomegaly and overt right-sided heart failure. A thorough history is important and should include a search for additional risk factors for lung disease and pulmonary hypertension (PH) such as smoking, indoor air pollution, left-sided cardiac disease and sleep disordered breathing. Twelve-lead electrocardiogram, chest X-ray and echocardiography can be used as screening tools. A definitive diagnosis should be made with right-sided heart catheterization using a modified mean pulmonary artery pressure of at least 30 mm Hg, differing from the 25 mm Hg used for other types of PH. Treatment of HAPH includes descent to a lower altitude whenever possible, oxygen therapy and the use of medications such as endothelin receptor antagonists, phosphodiesterase 5 blockers, fasudil and acetazolamide. Some recent evidence suggests that iron supplementation may also be beneficial. However, it is important to note that the scientific literature lacks long-term randomized controlled data on the pharmacologic treatment of HAPH. Thus, an individualized approach to treatment and informing the patients regarding the benefits and risks of the selected treatment regimen are essential

Painless Livedoid Vasculopathy in a Patient with G20210A Prothrombin Gene Mutation

87 year old Caucasian female with chronic painless non-healing ulcers over malleoli was admitted to the hospital. On a physical examination, there were two bilateral and laterally located malleoli ulcers with no discharge. A thorough work up was done: lower extremities venous and arterial Doppler ultrasound did not show any evidence of venous and arterial disease respectively. Heterozygous G20210A Prothrombin gene mutation was found, and the patient was started on anticoagulation. This case reports highlights a possibility of a painless livedoid vasculopathy presentation in a patient without significant past thrombotic events. Therefore, it is important to consider livedoid vasculopathy in the differential in a patient with painless ulcerative, atrophic and/or nodular skin lesions over the shins and malleoli

The Role of Renal Replacement Therapy in the Management of Pharmacologic Poisonings

Pharmacologic toxicities are common and range from mild to life-threatening. The aim of this study is to review and update the data on the role of renal replacement therapy (RRT) in the management of various pharmacologic poisonings. We aim to provide a focused review on the role of RRT in the management of pharmacological toxicities. Relevant publications were searched in MEDLINE with the following search terms alone or in combination: pharmacologic toxicity, hemodialysis, hemofiltration, renal replacement therapy, toxicology, poisonings, critical illness, and intensive care. The studies showed that a pharmacologic substance should meet several prerequisites to be deemed dialyzable. These variables include having a low molecular weight (\u3c 500 Da) and low degree of protein binding (\u3c 80%), being water-soluble, and having a low volume of distribution (\u3c 1 L/kg). RRT should be strongly considered in critically ill patients presenting with toxic alcohol ingestion, salicylate overdose, severe valproic acid toxicity, metformin overdose, and lithium poisoning. The role of RRT in other pharmacologic toxicities is less certain and should be considered on a case-by-case basis

Gastrointestinal Stromal Tumor Induced Hypercalcemia

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D3 mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D3. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor described in literature resulting in hypercalcemia. In our case, the mechanism of hypercalcemia was thought to be related to overproduction of 1,25-dihydroxyvitamin by tumor cells. The patient had a favorable response to imatinib with normalization of serum calcium level. Unfortunately, she developed fluid retention due to imatinib which was discontinued resulting in relapse of hypercalcemia that was resistant to all other treatment options

The Role of Sodium Bicarbonate in the Management of Some Toxic Ingestions

Adverse reactions to commonly prescribed medications and to substances of abuse may result in severe toxicity associated with increased morbidity and mortality. According to the Center for Disease Control, in 2013, at least 2113 human fatalities attributed to poisonings occurred in the United States of America. In this article, we review the data regarding the impact of systemic sodium bicarbonate administration in the management of certain poisonings including sodium channel blocker toxicities, salicylate overdose, and ingestion of some toxic alcohols and in various pharmacological toxicities. Based on the available literature and empiric experience, the administration of sodium bicarbonate appears to be beneficial in the management of a patient with the above-mentioned toxidromes. However, most of the available evidence originates from case reports, case series, and expert consensus recommendations. The potential mechanisms of sodium bicarbonate include high sodium load and the development of metabolic alkalosis with resultant decreased tissue penetration of the toxic substance with subsequent increased urinary excretion. While receiving sodium bicarbonate, patients must be monitored for the development of associated side effects including electrolyte abnormalities, the progression of metabolic alkalosis, volume overload, worsening respiratory status, and/or worsening metabolic acidosis. Patients with oliguric/anuric renal failure and advanced decompensated heart failure should not receive sodium bicarbonate

An association between TRP64ARG polymorphism of the B3 adrenoreceptor gene and some metabolic disturbances

<p>Abstract</p> <p>Backgrounds</p> <p>B3 adrenoreceptors (ADRB3) are abundant in adipose tissue and play the role in its metabolism and lipolysis. Some variants of the ADRB3 gene may predispose subjects for the development obesity and metabolic abnormalities in the setting of modern sedentary lifestyle. ADRB3 gene polymorphism association with metabolic disturbances has never been studied before in the ethnic Kyrgyz population.</p> <p>Aim</p> <p>To study an association between Trp64Arg polymorphism of the ADRB3 and metabolic syndrome (MS) components in an ethnic Kyrgyz group.</p> <p>Materials and methods</p> <p>213 Ethnic Kyrgyz volunteers over the age of 30 were enrolled in the study. The assessment plan for each individual comprised of general physical and anthropometric exams as well as laboratory tests (glucose, lipid panel, insulin) and genotyping by Trp64Arg polymorphism of the ADRB3. MS diagnosis was consistent with modified ATP III criteria (2005). Logistic regression analysis was performed to test the potential independent association between Arg64 allele with obesity, abdominal obesity (AO) and arterial hypertension (AH).</p> <p>Results</p> <p>Trp64Arg polymorphism of the ADRB3 was assessed in 213 individuals (145 men, 68 women) aged 30-73 (mean age 50.7 ± 7.6). Arg64 allele frequency was 0.239; ADRB3 genotype distribution among participants was: Trp64 homozygotes 54.5%, Trp64Arg 43.2% and Arg64 homozygotes 2.3%. There was an association between Trp64Arg и Arg64Arg genotypes and higher BMI, WC and obesity frequency (p < 0.00009), AO (p < 0.01), type 2 diabetes mellitus (DM) (p < 0.005) and lower high density cholesterol (HDL-C) level (p < 0.03). The logistic regression analysis showed the correlation of the Arg64 allele with obesity (OR 3.159; 95% CI 1.789-5.577) and AO (OR 1.973; 95% CI 1.118-3.481). The association between Arg64 allele and AH lost its significance after adjustment for obesity.</p> <p>Conclusion</p> <p>Arg64 allele of the ADRB3 gene in the studied group has an association with MS components such as obesity, AO and decreased HDL-C level.</p

A Combination of Two Rare Coronary Anomalies Makes It Even Rarer: Right Sided Single Coronary Artery with Dual Left Anterior Descending Artery

An 82-year-old female with history of hyperlipidemia and hypertension presented to the clinic with chief complaint of nonradiating chest tightness accompanied by exertional dyspnea. Cardiac catheterization showed the absence of left coronary system; the entire coronary system originated from the right aortic sinus as a common trunk which then gave off the right coronary artery and the left main coronary artery. Cardiac catheterization demonstrated also another rare coronary anomaly: dual left anterior descending artery. Patient underwent percutaneous coronary intervention and subsequent multidetector computed tomography angiography confirmed the above angiography findings. Patient was subsequently discharged home on double antiplatelet therapy with aspirin and clopidogrel and has been asymptomatic since then

Isolated \u3cem\u3eSporothrix schenckii\u3c/em\u3e Monoarthritis

Sporothrix schenkii sensu lato is a rare cause of arthritis. Its course is indolent with lack of constitutional symptoms resulting in delayed presentation and diagnosis. It is a dimorphic fungus found ubiquitously in sphagnum moss, decaying vegetation, soil, and hay. Inoculation of dirt into the skin and soft tissues and, in rare instances, inhalation of aerosolized conidia from soil and plants can lead to infection. Subacute and chronic involvement of skin and subcutaneous tissues is the most common manifestation of sporotrichosis in immunocompetent hosts. In patients with underlying risk factors (HIV, alcoholism, diabetes mellitus, organ transplant patients, immunosuppressive medications, steroids, and malignancies), it can often have disseminated visceral, osteoarticular, meningeal, and pulmonary involvement. Sporothrical arthritis most commonly infects knee joint followed by hand and wrist joints. A culture of Sporothrix schenkii sensu lato is the gold standard for the diagnosis of sporotrichosis. Itraconazole is the drug of choice for osteoarticular sporotrichosis. We present a case of sporotrichal arthritis in a patient without skin or lymph node involvement who underwent treatment with itraconazole resulting in resolution of his symptoms