Acetazolamide: a treatment for chronic mountain sickness

RATIONALE: Chronic mountain sickness or Monge's disease is characterized by an excessive polycythemia in high-altitude dwellers, with a prevalence of 5 to 18% above 3,200 m. To date, no pharmacologic treatment is available. OBJECTIVES: We evaluated the efficacy of acetazolamide in the treatment of chronic mountain sickness and the importance of nocturnal hypoxemia in its pathophysiology. METHODS: A double-blind placebo-controlled study was performed in three groups of patients from Cerro de Pasco, Peru (4,300 m), treated orally for 3 weeks with placebo (n = 10), 250 mg of acetazolamide (n = 10), or 500 mg of acetazolamide (n = 10), daily. RESULTS: Acetazolamide decreased hematocrit by 7.1% (p < 0.001) and 6.7% (p < 0.001), serum erythropoietin by 67% (p < 0.01) and 50% (p < 0.001), and serum soluble transferrin receptors by 11.1% (p < 0.05) and 3.4% (p < 0.001), and increased serum ferritin by 540% (p < 0.001) and 134% (p < 0.001), for groups treated with 250 and 500 mg of acetazolamide, respectively. Acetazolamide (250 mg) increased nocturnal arterial O(2) saturation by 5% (p < 0.01) and decreased mean nocturnal heart rate by 11% (p < 0.05) and the number of apnea-hypopnea episodes during sleep by 74% (p < 0.05). The decrease in erythropoietin was attributed mainly to the acetazolamide-induced increase in ventilation and arterial O(2) saturation. CONCLUSIONS: Acetazolamide, the first efficient pharmacologic treatment of chronic mountain sickness without adverse effects, reduces hypoventilation, which may be accentuated during sleep, and blunts erythropoiesis. Its low cost may allow wide development with a considerable positive impact on public health in high-altitude regions.     

Clinical outcomes of COVID-19 treated with remdesivir across the continuum of care

Introduction

During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined.

Methods

Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals.

Results

Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06–0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27–2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45–2.95, p < 0.001).

Conclusions

This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.     

Targeted therapy for the treatment of advanced non-small cell lung cancer: a review of the epidermal growth factor receptor antagonists

Lung cancer is the most common cause of cancer death. The vast majority of patients present with non-small cell lung cancer (NSCLC) in advanced inoperable stages. The current first-line treatment for patients with advanced NSCLC includes chemotherapy and palliative radiotherapy, but most patients relapse and eventually succumb to the disease. Advances in our knowledge of cancer cell biology have led to the development of specific molecular-targeted therapeutic agents. Mutations in the epidermal growth factor receptor (EGFR) have been identified in NSCLC cells, and overexpression of the EGFR and its ligands is a common feature of many cancers; therefore, EGFR has become an attractive target for various antitumor strategies. Aberrant signaling from the EGFR is known to be important in the development and progression of NSCLC. Two oral EGFR inhibitors, gefitinib and erlotinib, are small-molecule agents that selectively inhibit the intracellular tyrosine kinase activity of the EGFR. Both have demonstrated antitumor activity in patients with advanced NSCLC who have failed all prior treatment regimens. In addition, the anti-EGFR monoclonal antibody cetuximab has shown promising activity in both first-line and second-line settings in patients with advanced NSCLC. Furthermore, patients with severe comorbidities who would not be eligible for systemic chemotherapy are candidates for these targeted therapies. Finally, these agents have also been shown to be effective for relieving symptoms, maintaining stable disease, and improving quality of life without the adverse events that may be associated with cytotoxic cancer therapies. This report will review the mechanism of action, indications, contraindications, patient selection, and efficacy and side effects of this new class of compounds. It is important for pulmonologists to be aware of this class of compounds, as they can provide benefit to patients with NSCLC who may not have been previously considered for antitumor therapy.     

Association between genital tract cytomegalovirus infection and bacterial vaginosis

Women with sexually transmitted diseases (STDs) and bacterial vaginosis (BV) have increased rates of cytomegalovirus (CMV) seroprevalence and CMV seroconversion. To characterize the association between genital tract CMV infection and BV, vaginal wash specimens from 52 women attending an STD clinic were analyzed. Significantly more women with BV shed CMV in the lower genital tract than did women without BV. In addition, most of the women who were shedding CMV were infected with >1 virus strain. These results suggest that local CMV replication and infection with multiple CMV strains is facilitated by the presence of BV.     

Natural history of patients hospitalized for management of cirrhotic ascites.

BACKGROUND & AIMS: Since the International Ascites Club published the diagnostic criteria of refractory ascites (RA) and hepatorenal syndrome (HRS), there have been few studies assessing the natural history of ascites. The aims of this study were to define the natural history of cirrhotic ascites and to identify prognostic factors for dilutional hyponatremia (DH), RA, HRS, and survival. METHODS: Two hundred sixty-three consecutive cirrhotic patients were followed for 40.9 +/- 2.6 months after their first significant ascites. RESULTS: During follow-up 74 (28.1%) patients developed DH, 30 (11.4%) RA (diuretic-resistant in 2 cases and diuretic-intractable because of the development of diuretic-induced complications in 28 cases), and 20 (7.6%) HRS (type 1, 7; type 2, 13). The 5-year probability of DH, RA, and HRS development was 37.1%, 11.4%, and 11.4%, respectively. The probability of survival at 1 and 5 years was 85% and 56.5%, respectively. The independent predictors for survival were baseline age, baseline Child-Pugh score, and DH development. The 1-year probability of survival after developing DH, RA, and type 2 HRS was 25.6%, 31.6%, and 38.5%, respectively. In contrast, the mean survival was only 7 +/- 2 days in those patients developing type 1 HRS. CONCLUSIONS: (1) The survival of cirrhotic patients with first episode of ascites is relatively high, and it is mainly influenced by age and Child-Pugh score at the time of ascites decompensation, as well as by DH development. (2) The probability of RA and HRS development is relatively low, but they are associated with a poor prognosis.     

Improvement of child survival in Mexico: the diagonal approach

Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.     

Reactivation of cardiac Chagas' disease in acquired immune deficiency syndrome

We report the case of a 29-year-old man who developed acute congestive heart failure secondary to cardiac Chagas' disease in the setting of Trypanosoma cruzi reactivation by acquired immune deficiency syndrome.     

Treatment of hyperphosphatemia with sevelamer in patients with chronic renal failure

Sevelamer is a recent phosphate binder that is mineral-free, and represents a great advance in the treatment of hyperphosphatemia in patients with hypercalcemia and/or gastric intolerance to calcium-based phosphate binders. The communications about the experience with the use of sevelamer in patients non-yet in dialysis is scanty. The aim of our study is to investigate retrospectively the gastrointestinal tolerance of sevelamer, their efficacy as phosphate binder and other parameters in a group of 89 patients with chronic renal failure in predialysis. We have analysed the effects of sevelamer at baseline and after 1, 3 and 6 months on the following data and parameters: calcium, phosphate, intact PTH, venous bicarbonate, urea, creatinine, creatinine clearance, side-effects, number of patients that were discontinued, and co-treatment during the study period with phosphate-based binders, calcitriol, lipid-lowering drugs and sodium bicarbonate. RESULTS: 19 patients (21.3%) refused to continue with sevelamer at the first month (16 patients had digestive intolerance and 3 several symptoms). Serum phosphate fell at 3 months (5 +/- 0.8 mg/dl basal vs 4.8 +/- 0.7 mg/dl, p = 0.02) and 6 months (5 +/- 0.8 mg/dl basal vs 4.7 +/- 0.9 mg/dl, p = 0.07). Serum calcium fell at 6 months (9.8 +/- 0.7 mg/dl basal vs 9.4 +/- 0.6 mg/dl, p = 0.03). Venous bicarbonate and iPTH were unchanged, but the quantity of sodium bicarbonate administered increased significantly. Blood cholesterol fell at 1 months (193 +/- 49 mg/dl basal vs 173 +/- 52 mg/dl, p = 0.001) and 3 months (205 +/- 49 mg/dl basal vs 170 +/- 49 mg/dl, p = 0.004), in spite of a significant reduction of the dose of statins. CONCLUSIONS: Sevelamer is an effective phosphate binder in predialysis patients and also reduces significantly the serum cholesterol, improving the blood lipid profile. The levels of venous bicarbonate remained unchanged, at expenses of an increment in the dose of sodium bicarbonate supplementation.     

Primary pulmonary lymphoma presenting as a pulmonary mass with cavitation

Primary pulmonary lymphoma is a rare entity usually formed of B-type cells, usually low-grade and composed of mucosal- or bronchial-associated lymphoid tissue. High-grade primary pulmonary lymphomas usually occur in immunodeficient patients who mostly present with respiratory and nonspecific symptoms. A chest x-ray may show a pulmonary mass or atelectasis and pleural effusion. In such cases, the prognosis is worse than for low-grade pulmonary lymphomas; survival is 8 to 10 years and there is a higher probability of local progression or metastasis. We report the case of an immunocompetent 76-year-old patient who had a pulmonary mass with cavitation secondary to a large B-cell primary pulmonary lymphoma. After the fourth session of chemotherapy the pulmonary mass was reduced in size and an aspergilloma was seen to have developed in the residual cavity. A review of the literature revealed this case to be anecdotal as it is extremely infrequent for a primary pulmonary lymphoma to present in the form of a single mass with cavitation and with few symptoms.     

Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation

We studied the vascular effects of invasive human cytotrophoblasts in vivo by transplanting placental villi to the fifth mammary fat pads or beneath the kidney capsules of Scid mice. Over 3 weeks, robust cytotrophoblast invasion was observed in both locations. The architecture of the mammary fat pad allowed for detailed analysis of the cells' interactions with resident murine blood vessels, which revealed specific induction of apoptosis in the endothelial cells and smooth muscle walls of the arterioles. This finding, and confirmation of the results in an in vitro coculture model, suggests that a parallel process is important for enabling cytotrophoblast endovascular invasion during human pregnancy. Cytotrophoblast invasion of the kidney parenchyma was accompanied by a robust lymphangiogenic response, while in vitro, the cells stimulated lymphatic endothelial cell migration via the actions of VEGF family members, FGF, and TNF-alpha. Immunolocalization analyses revealed that human pregnancy is associated with lymphangiogenesis in the decidua since lymphatic vessels were not a prominent feature of the nonpregnant endometrium. Thus, the placenta triggers the development of a decidual lymphatic circulation, which we theorize plays an important role in maintaining fluid balance during pregnancy, with possible implications for maternal-fetal immune cell trafficking.