The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection.

Background: SARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium <135 mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20-37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyse the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19. Methods: Observational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March-May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge. Results: 91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72-96 h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio 0.165; 95% confidence interval: 0.018-0.686; p = 0.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, p = 0.041). Conclusion: We conclude that persistence of hyponatremia at 72-96 h of hospital admission was associated with higher mortality in patients with SARS-Cov-2.

Introduccion: La infección por SARS-CoV-2 se asocia con frecuencia con hiponatremia (sodio plasmático <135 mmol/l), relacionándose con peor pronóstico. La incidencia de la hiponatremia se estima en 20­37% según las series, pero no existen datos sobre el pronóstico tras la corrección de la hiponatremia. Por ello, nuestros objetivos fueron: analizar la incidencia y gravedad de la hiponatremia al ingreso hospitalario, y determinar la asociación de dicha hiponatremia con el pronóstico del COVID-19. Material y método: Estudio de cohorte observacional y retrospectivo. Se incluyeron pacientes que ingresaron con diagnóstico de infección por COVID-19 e hiponatremia, en el periodo marzo-mayo 2020. Registramos variables epidemiológicas, demográficas, clínicas, analíticas y radiológicas de la infección por SARS-CoV-2 e hiponatremia al momento del diagnóstico y durante la hospitalización. El seguimiento clínico comprendió desde el ingreso hasta el exitus o el alta. Resultados: 91 pacientes (21,8%) de los 414 ingresados por infección del SARS-CoV-2 presentaron hiponatremia (81,32% hiponatremia leve, 9,89% moderada y 8,79% grave). La ausencia de corrección de la hiponatremia a las 72­96 horas del ingreso hospitalario estuvo asociado a mayor mortalidad en los pacientes con COVID-19 (OR 0,165; 95% intervalo de confianza: 0,018­0,686; p = 0,011). Fallecieron 19 pacientes (20,9%). Se observó un aumento de la mortalidad en pacientes con hiponatremia grave en comparación con hiponatremia moderada y leve durante el ingreso (37,5% versus 11,1% versus 8,1%, respectivamente, p = 0,041). Conclusiones: La persistencia de la hiponatremia tras las primeras 72­96 horas del ingreso hospitalario fue asociada a mayor mortalidad+- en los pacientes con SARS-Cov-2.

Impacto de la corrección temprana de la hiponatremia en el pronóstico de la infección del síndrome respiratorio agudo grave del coronavirus 2 (SARS-CoV-2) / The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection

IntroducciónLa infección por el coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) se asocia con frecuencia con hiponatremia (sodio plasmático<135mmol/l), relacionándose con peor pronóstico. La incidencia de la hiponatremia se estima en 20-37% según las series, pero no existen datos sobre el pronóstico tras la corrección de la hiponatremia. Por ello, nuestros objetivos fueron: analizar la incidencia y gravedad de la hiponatremia al ingreso hospitalario y determinar la asociación de dicha hiponatremia con el pronóstico de la enfermedad por coronavirus de 2019 (COVID-19).Material y métodoEstudio de cohorte observacional y retrospectivo. Se incluyeron pacientes que ingresaron con diagnóstico de infección por COVID-19 e hiponatremia en el periodo marzo-mayo de 2020. Registramos variables epidemiológicas, demográficas, clínicas, analíticas y radiológicas de la infección por SARS-CoV-2 e hiponatremia en el momento del diagnóstico y durante la hospitalización. El seguimiento clínico comprendió desde el ingreso hasta el exitus o el alta.ResultadosNoventa y un pacientes (21,8%) de los 414 ingresados por infección del SARS-CoV-2 presentaron hiponatremia (81,32% hiponatremia leve, 9,89% moderada y 8,79% grave). La ausencia de corrección de la hiponatremia a las 72-96horas del ingreso hospitalario estuvo asociado a mayor mortalidad en los pacientes con COVID-19 (odds ratio 0,165; 95% intervalo de confianza: 0,018-0,686; p=0,011). Fallecieron 19 pacientes (20,9%). Se observó un aumento de la mortalidad en pacientes con hiponatremia grave en comparación con hiponatremia moderada y leve durante el ingreso (37,5% versus 11,1% versus 8,1%, respectivamente; p=0,041).ConclusionesLa persistencia de la hiponatremia tras las primeras 72-96horas del ingreso hospitalario se asoció a mayor mortalidad en los pacientes con SARS-CoV-2. (AU)

IntroductionSARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium<135mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20–37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyze the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19.Material and methodObservational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March–May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge.Results91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72–96h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio .165; 95% confidence interval: .018-.686; P=.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, P=.041).ConclusionsWe conclude that persistence of hyponatremia at 72–96h of hospital admission was associated with higher mortality in patients with SARS-CoV-2. (AU)

The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection. / Impacto de la corrección temprana de la hiponatremia en el pronóstico de la infección del síndrome respiratorio agudo grave del coronavirus 2 (SARS-CoV-2).

INTRODUCTION: SARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium<135mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20-37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyze the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19. MATERIAL AND METHOD: Observational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March-May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge. RESULTS: 91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72-96h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio .165; 95% confidence interval: .018-.686; P=.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, P=.041). CONCLUSIONS: We conclude that persistence of hyponatremia at 72-96h of hospital admission was associated with higher mortality in patients with SARS-CoV-2.

Multiple brown tumors-Forgotten pathology in times of calcimimetics: A case report and literature review.

Multiple brown tumors represent a rare variant of osteitis fibrosa cystica. Brown tumors are associated with primary, secondary, or tertiary hyperparathyroidism. Brown tumors have been reported in patients with chronic kidney disease resulting in mineral and bone disorders. Chronic kidney disease resulting in mineral and bone disorder is a result of increased osteoclast activity and excessive production of parathormone due to parathyroid gland hyperactivity. Brown tumors are frequently overlooked in patients with end-stage renal disease since calcimimetics and vitamin D analogs were introduced as pharmacological therapy for secondary hyperparathyroidism. We present a case of a 79 year-old pre-dialysis woman, with multiple brown tumors secondary to a parathyroid adenoma despite being treated with cinacalcet for secondary hyperparathyroidism. In addition, we review the corresponding literature.

Ambulatory Blood Pressure Monitoring in HIV-Infected Patients: Usefulness for Cardiovascular Risk Assessment.

BACKGROUND: There is a lack of consensus regarding the risk of hypertension in HIV-infected patients compared to the general population. Ambulatory blood pressure monitoring (ABPM) is the most accurate method for the hypertension diagnosis. Nevertheless, it is rarely used in HIV clinical care. MATERIALS AND METHODS: All HIV-infected patients who underwent 24 hours ABPM were included. The agreement between office blood pressure (BP) readings and ABPM was analyzed. The rate of patients with masked hypertension (MH), isolated clinical hypertension, and nocturnal hypertension was obtained. Furthermore, it was analyzed if the differences between both methods may affect the cardiovascular risk (CVR) assessment. RESULTS: A total of 116 patients were included. The κ coefficient between office BP and ABPM was 0.248. Over a quarter of the cohort was diagnosed with MH-25.8% (CI 95% 17.7%-34.0%), and 12% (CI 95%: 6.1%-16.1%) was diagnosed with ICH. Moreover, 19% of patients had hypertension exclusively during the night. The patients classified as low risk according to the CVR scores had a different diagnosis with ABPM than with office BP (P < .001). CONCLUSIONS: The agreement between office BP and ABPM was low in HIV-infected patients. Ambulatory BP monitoring is useful in HIV-infected patients as a hypertension diagnosis method, especially among patients classified as low risk.

Infección diseminada por Propionibacterium acnes en un varón de 42 años con infección por el VIH / Disseminated Propionibacterium acnes infection in a 42-year-old HIV-positive man

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Overall and cause-specific excess mortality in HIV-positive persons compared with the general population: Role of HCV coinfection.

We aimed to estimate overall and cause-specific excess mortality of HIV-positive patients compared with the general population, and to assess the effect of risk factors.We included patients aged >19 years, recruited from January 1, 2004 to May 31, 2014 in Cohort of the Spanish Network on HIV/AIDS Research. We used generalized linear models with Poisson error structure to model excess mortality rates.In 10,340 patients, 368 deaths occurred. Excess mortality was 0.82 deaths per 100 person-years for all-cause mortality, 0.11 for liver, 0.08 for non-AIDS-defining malignancies (NADMs), 0.08 for non-AIDS infections, and 0.02 for cardiovascular-related causes. Lower CD4 count and higher HIV viral load, lower education, being male, and over 50 years were predictors of overall excess mortality. Short-term (first year follow-up) overall excess hazard ratio (eHR) for subjects with AIDS at entry was 3.71 (95% confidence interval [CI] 2.66, 5.19) and 1.37 (95% CI 0.87, 2.15) for hepatitis C virus (HCV)-coinfected; medium/long-term eHR for AIDS at entry was 0.90 (95% CI 0.58, 1.39) and 3.83 (95% CI 2.37, 6.19) for HCV coinfection. Liver excess mortality was associated with low CD4 counts and HCV coinfection. Patients aged ≥50 years and HCV-coinfected showed higher NADM excess mortality, and HCV-coinfected patients showed increased non-AIDS infections excess mortality.Overall, liver, NADM, non-AIDS infections, and cardiovascular excesses of mortality associated with being HIV-positive were found, and HCV coinfection and immunodeficiency played significant roles. Differential short and medium/long-term effects of AIDS at entry and HCV coinfection were found for overall excess mortality.

Hepatic Safety of Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate Fixed-Dose Single-Tablet Regimen in HIV-Infected Patients with Active Hepatitis C Virus Infection: The hEPAtic Study.

OBJECTIVES: The aim of this study was to evaluate the frequency of transaminase elevations (TE) and total bilirubin elevations (TBE) during the first year of therapy with a single tablet regimen including RPV/FTC/TDF (EPA) in HIV/hepatitis C virus (HCV)-coinfected subjects in clinical practice. METHODS: In a retrospective analysis, HIV/HCV-coinfected subjects who started EPA at 17 centres throughout Spain were included as cases. Subjects who started an antiretroviral therapy (ART) other than EPA during the study period at the same hospitals were randomly selected as controls in a 1:2 ratio. Primary outcome variables were grade (G) 3-4 TE and G4 TBE. RESULTS: Of the 519 subjects included, 173 individuals started EPA. Nine (5.2%) subjects of the EPA group and 49 (14.2%) controls were naïve to ART. The median (Q1-Q3) follow-up was 11.2 (9.7-13.9) months. TE was observed in 2 [1.2%; 95% confidence interval (CI): 0.14%-4.1%] subjects receiving EPA and 11 (3.2%; 95%CI: 1.6%-5.6%) controls (p = 0.136), all events were G3. No patient discontinued ART due to TE. One (0.6%; 95%CI: 0.01%-3.1%) subject on EPA and 8 (2.3%; 95%CI: 1%-4.5%) subjects in the control group developed TBE (p = 0.141), without developing any other hepatic event during follow-up. Three (2.3%) subjects with cirrhosis versus 10 (3.1%) without cirrhosis showed G3-4 TE (p = 0.451). CONCLUSION: The frequency of severe liver toxicity in HIV/HCV-coinfected subjects receiving EPA under real-life conditions is very low, TE were generally mild and did not lead to drug discontinuation. All these data suggest that EPA can be safely used in this particular subpopulation.

Hepatic safety of RPV/FTC/TDF single tablet regimen in HIV/HCV-coinfected patients. Preliminary results of the hEPAtic Study.

INTRODUCTION: Although hepatotoxicity related to antiretroviral treatment (ART) has become less frequent, hepatotoxic events, such as transaminase elevations (TE), are still a matter of concern. RPV/FTC/TDF (EPA) is a new single tablet regimen which is widely used in real life practice. Clinical trials showed an adequate profile of liver safety in the sub-population of HIV/HCV-coinfected patients receiving rilpivirine. However, the number of individuals included in these analyses is low (1). The aim of this ongoing study is to evaluate the incidence of TE and total bilirubin elevations (TBE) during the first 48 weeks of EPA-based therapy in a large population of HIV/HCV-coinfected subjects outside of clinical trials. PATIENTS AND METHODS: This is a retrospective analysis of HIV/HCV-coinfected subjects who started EPA at the infectious diseases units of 14 centres throughout Spain, included as cases. Subjects who started an ART different to EPA during the study period at the same hospitals were selected as controls. The primary outcome variables were grade 3 or 4 TE and grade 4 TBE. RESULTS: Of the 191 patients included, 31 (16.2%) subjects were naïve to ART. Eighty-seven individuals started EPA and the remaining ones were controls. The most common NRTI backbone among the controls was TDF/FTC [59 (56.7%) patients] followed by NRTI-sparing regimens [24 (23.1%) individuals] and ABC/3TC [17 (16.3%) subjects]. Among controls, 67 (64.4%) started a ritonavir-boosted protease inhibitor, mainly DRV/r [41 (39.4%) patients] followed by ATV/r [16 (15.4%) subjects]. EFV, ETV and RAL were started in 16 (15.4%), 12 (11.5%) and 13 (12.5%) subjects, respectively. The median (Q1-Q3) follow-up was 5.79 (3.65-8.61) months for the cases and 11.44 (5.8-12.88) months for the controls. TE was observed in two (2.3%) cases versus five (4.8%) controls (p=0.358), accounting for a density of incidence of 4.32/100 person-years versus 5.51/100 person-years [incidence rate difference (95% confidence interval): -1.88 (-9.95-6.2), p=0.354]. All TE were grade 3 and no patient discontinued ART due to TE. None of the cases developed TBE versus four (3.8%) controls, all of them receiving ATV/r. CONCLUSIONS: The frequency of grade 3-4 TE associated with EPA in HIV/HCV-coinfected patients under real life conditions is very low. In addition, TE in HIV/HCV-coinfected patients treated with EPA are usually mild and do not lead to treatment discontinuation. TBE was not seen in patients taking EPA. All these data confirm that EPA is safe in this particular subpopulation.

Resistance mutations in protease gene at baseline are not related to virological failure in patients treated with darunavir/ritonavir monotherapy.

INTRODUCTION: Monotherapy with darunavir plus ritonavir (DRV/r) is a good maintenance strategy for suppressed HIV-infected patients. The clinical trials designed to prove the efficacy of PI/r do not include patients with resistance mutation in protease gene [1,2]. Sometimes in routine practice, basically to avoid NRTIs toxicity, monotherapy with DRV/r is used despite PI resistance mutations. The aim of this study is to know the effect of previous protease resistance mutation on DRV/r monotherapy efficacy. MATERIALS AND METHODS: We designed an observational cohort study of adults in treatment with DRV/r monotherapy in a tertiary Spanish hospital since 2011 to 2014. Demographic data and clinical outcomes were described. The analysis of efficacy was done according to the snapshot algorithm (defining virological failure as viral load >50 copies/mL, ITTe, at 48 and 96 weeks). We analyzed the difference of efficacy between patients with and without baseline resistance mutations at 48 and 96 weeks by using the χ(2) test; and during the follow-up by using the Kaplan-Meier test. The statistical analysis was done with SPSS 17.0. RESULTS: Eighty-nine patients were included in the cohort but 14 were excluded because they had not reached more than six months with monotherapy. The cohort was composed mainly by men (78%), the medium age was 51 years (SD±10), 35% were MSM and 19% were former IDU. Twenty-four patients (35%) had a previous diagnosis of AIDS. The mean time taking NRTIs was 10.5 years (SD±5.4). Sixty-four patients (85%) had been treated with PI in the past. Previous failure with PI had been reported in 15 (20%). A resistance mutation test had been done at baseline in 45 patients (51%). Twenty-two patients (29%) had some mutations in protease gene, 10 patients (13%) had major mutations and 1 patient had some mutations of resistance for darunavir (I64V). At 48 weeks, 93% (CI 95% 86-98%) had VL<50 copies/mL, and 79% (CI 95% 67-89%) at 96 weeks. There were not differences between patients with or without resistance mutations (p=0.53). After a median follow-up of 70 weeks, 88% of patients remain free of virological failure and there were not differences between both groups. CONCLUSIONS: According to these data, previous resistance mutations in the protease gene, which do not affect darunavir, are not related with the efficacy in patients treated with DRV/r monotherapy.

Efficacy and tolerability of darunavir/ritonavir in combination with abacavir/lamivudine: an option in selected HIV-infected patients.

OBJECTIVE: To evaluate the safety and efficacy of abacavir/lamivudine (ABC/3TC) plus darunavir/ritonavir (DRV-RTV) in experienced patients. METHODS: The study was conducted in Spain in 6 hospital clinics and involved HIV-positive patients who needed to change their antiretroviral treatment (ART) for several reasons. They started fixed-dose combination (FDC) ABC/3TC (600 mg/300 mg), DRV (400 mg 2 tablets qd), and RTV (100 mg) from January 2010 to April 2012. The patients were evaluated at baseline and at intervals of 3 to 6 months, and at least once at the end of the follow-up. Adverse events (AEs), concurrent medications, HIV-associated conditions, and adherence were also assessed at each visit. RESULTS: Seventy-six patients were included from 6 sites (60 male). Median CD4 cell count was 479/mm3, and the median time on follow-up was 10.1 months. Thirty-eight patients (50%) have reached 48 weeks of follow-up and 32 (84.2 %) have achieved HIV RNA <50 copies/mL in this period. Immunological recovery was observed with a median CD4 count increase of 119 cells/mm3 by week 48. There were no patients who discontinued the study treatment due to AEs, and all the toxicities that lead to change ART at baseline were resolved or improved substantially. CONCLUSION: This study showed that the study regimen provided consistent antiviral and immunological responses until 48 weeks. The antiretroviral effect of the regimen was observed in subsets of patients evaluated, including those with high baseline HIV-1 RNA levels and virological failure and those with switching, with little or no difference across subgroups.