Metabolic effects of switching to Biktarvy (B/F/TAF) in patients with HIV-1 treated with antiretroviral regimens that do not include tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF): The Metabic study.

BACKGROUND: Studies on switching to tenofovir alafenamide (TAF)-based regimens raise concerns about a worse metabolic profile in people with HIV, even though most received tenofovir disoproxil fumarate (TDF) in their previous regimen. This study aims to evaluate changes in lipid fractions, glucose, and serum markers for hepatic steatosis (HS) after switching from a TDF- or TAF-sparing regimen to bictegravir/emtricitabine/TAF (B/F/TAF). METHODS: We performed a retrospective cohort study of people with HIV who switched to B/F/TAF from TDF- or TAF-sparing regimens between January 2019 and May 2022 with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were changes in lipid fractions at 12 months and changes in other metabolic parameters (glucose, creatinine, and HS based on the triglyceride-to-glucose [TyG] ratio at 6 and 12 months). Changes were analysed using mixed linear regression models with random intercept and time as a fixed effect. RESULTS: The study included 259 people with HIV (median age 55 [interquartile range (IQR) 47-60] years; 80% male; 88% Caucasian; CD4+ T-cell count 675 [IQR 450-880] cells/mm3; 84.3% HIV-RNA <50 copies/mL). In total, 63 patients (30%) had hypertension, 93 (44%) dyslipidaemia, 30 (14%) diabetes, and 45% obesity/overweight. Most (60%) switched from integrase inhibitor-based regimens, and 21% switched from a boosted regimen. At 6 months, significant reductions were observed in total cholesterol (-7.64 mg/dL [95% confidence interval (CI) -13.52 to -1.76; p = 0.002]), triglycerides (-23.4 [95% CI -42.07 to -4.65]; p = 0.003), and TyG ratio (-0.14 [95% CI -0.23 to -0.05]; p < 0.001). CONCLUSION: In our real-life cohort, the effect of switching TDF-/TAF-sparing regimens to triple therapy with B/F/TAF improved total cholesterol, triglycerides, and serum markers of HS at 6 months and was neutral for the remaining metabolic parameters at 12 months.

[Factors associated with mortality due to SARS-CoV-2 in the population over 75 years of age in the Community of Madrid]. / Factores asociados con la mortalidad por SARS-CoV-2 en la población mayor de 75 años de la Comunidad de Madrid.

Objective: Various studies have identified factors associated with risk of mortality in patients with SARS-CoV-2 infection. However, their sample size has often been limited and their results partially contradictory. This study evaluated factors associated with COVID-19 mortality in the population of Madrid over 75 years of age, in infected patients, and in hospitalized patients up to January 2021. Patients and methods: This population-based cohort study analyzed all residents of the Community of Madrid born before January 1, 1945 who were alive as of December 31, 2019. Demographic and clinical data were obtained from primary care electronic medical records (PC-Madrid), data on hospital admissions from the Conjunto Mínimo Básico de Datos (CMBD, Minimum Data Set), and data on mortality from the Índice Nacional de Defunciones (INDEF, National Death Index). Data on SARS-CoV-2 infection, hospitalization, and death were collected from March 1, 2020 to January 31, 2021. Results: A total of 587,603 subjects were included in the cohort. Of them, 41,603 (7.1%) had confirmed SARS-CoV-2 infection, of which 22,362 (53.7% of the infected individuals) were hospitalized and 11,251 (27%) died. Male sex and age were the factors most closely associated with mortality, though many comorbidities also had an influence. The associations were stronger in the analysis of the total population than in the analysis of infected or hospitalized patients. Mortality among hospitalized patients was lower during the second wave (33.4%) than during the first wave (41.2%) of the pandemic. Conclusion: Age, sex, and numerous comorbidities are associated with risk of death due to COVID-19. Mortality in hospitalized patients declined notably after the first wave of the pandemic.

Asthma exacerbations in a tertiary hospital: clinical features, triggers, and risk factors for hospitalization.

BACKGROUND: Risk factors for asthma exacerbations are not fully understood. The aim of this study was to determine the epidemiological and clinical characteristics of patients with an asthma exacerbation, potential triggers, and possible predictors of hospitalization. METHODS: A retrospective, non-interventional cohort study was conducted in adult patients who attended the Emergency Department of a tertiary hospital with an asthma exacerbation during 2014. RESULTS: 831 patients (888 events) were included. The highest number of episodes occurred in January and May. Respiratory infection was considered the trigger in 523 events. 34.21% had ≥260 eosinophils/mm3 (20.7%≥400 eosinophils/mm3), significantly associated with allergic asthma (p<0.0001). Risk factors for hospitalization were: older age [OR:1.58 (95% CI 1.46-1.71)]; no previous diagnosis of asthma [OR:1.40(95% CI 1.06-1.86)]; poorly controlled asthma[OR:1.78 (95% CI 1.10-2.88)]; respiratory infection [OR:2.65 (95% CI 1.95-3.62)]; and severe crisis with more treatment requirements. Of those asthmatics with ≥400 eosinophils/mm3, the rate of hospitalization was lower (p<0.001). CONCLUSION: Older age, absence of a previous asthma diagnosis, uncontrolled disease or concomitant COPD are frequent among patients presenting to the ED with asthma exacerbations. There were some features associated with higher risk of admission. Blood eosinophilia should be considered as a marker of asthma, but not as a predictor of hospitalization.

Vitamin C and thiamine for the treatment of refractory septic shock in surgical critically ill patients: a retrospective before-and-after study.

OBJECTIVE: This study aimed to evaluate whether early vitamin C and thiamine administration was associated with a lower 28-day and in-hospital mortality in surgical critically ill patients with refractory septic shock. METHODS: We performed a retrospective before-and-after study on patients with refractory septic shock. According to local protocol, hydrocortisone is initiated in case of refractory septic shock. In January 2017, the protocol was changed and vitamin C and thiamine were included. Patients who were admitted in 2015-2016 and 2017-2018 were included in the control and treatment groups, respectively. The primary end point was 28-day and in-hospital mortality. Secondary end points were ICU mortality, ICU and hospital length of stay, duration of vasopressors and mechanical ventilation, use of renal replacement therapy (RRT), and the modification in serum procalcitonin and SOFA score during the first 72 h. RESULTS: A total of 120 patients were included (58 in the treatment group and 62 in the control group). Log-rank test in Kaplan-Meier curves showed lower 28-day and in-hospital mortality over time in the treatment group (p=0.021 and p=0.035, respectively) but it not reached statistical significance in ICU mortality over time (p=0.100). The need of RRT was less frequent in treatment group (17.2% vs. 37.1%, p=0.024). There were no differences in other secondary outcomes. CONCLUSIONS: Intravenous vitamin C and thiamine administration in surgical patients with refractory septic shock may be associated with a lower 28-day and in-hospital mortality. Further prospective studies are needed in refractory septic shock.

Biochemical algorithm to identify individuals with ALPL variants among subjects with persistent hypophosphatasaemia.

BACKGROUND: Hypophosphatasia (HPP) is a rare and underdiagnosed condition characterized by deficient bone and teeth mineralization. The aim of this study was first, to evaluate the diagnostic utility of employing alkaline phosphatase (ALP) threshold levels to identify adults with variants in ALPL among individuals with persistently low ALP levels and second, to determine the value of also including its substrates (serum pyridoxal-5'-phosphate-PLP-and urinary phosphoetanolamine-PEA) for this purpose in order to create a biochemical algorithm that could facilitate the diagnostic work-up of HPP. RESULTS: The study population comprised 77 subjects with persistent hypophosphatasaemia. They were divided into two groups according to the presence (+GT) or absence (-GT) of pathogenic ALPL variants: 40 +GT and 37 -GT. Diagnostic utility measures were calculated for different ALP thresholds and Receiver Operating Characteristic (ROC) curves were employed to determine PLP and PEA optimal cut-off levels to predict the presence of variants. The optimal threshold for ALP was 25 IU/L; for PLP, 180 nmol/L and for PEA, 30 µmol/g creatinine. Biochemical predictive models were assessed using binary logistic regression analysis and bootstrapping machine learning technique and results were then validated. For ALP < 25 UI/L (model 1), the area under curve (AUC) and the 95% confidence intervals (CI) was 0.68 (95% CI 0.63-0.72) and it improved to 0.87 (95% CI 0.8-0.9), when PEA or PLP threshold levels were added (models 2 and 3), reaching 0.94 (0.91-0.97) when both substrates were included (model 4). The internal validation showed that the addition of serum PLP threshold levels to the model just including ALP improved significantly sensitivity (S) and negative predictive value (NPV) - 100%, respectively- with an accuracy (AC) of 93% in comparison to the inclusion of urinary PEA (S: 71%; NPV 75% and AC: 79%) and similar diagnostic utility measures as those observed in model 3 were detected when both substrates were added. CONCLUSIONS: In this study, we propose a biochemical predictive model based on the threshold levels of the main biochemical markers of HPP (ALP < 25 IU/L and PLP > 180 nmol/L) that when combined, seem to be very useful to identify individuals with ALPL variants.

Factors associated with mortality due to SARS-CoV-2 in the population over 75 years of age in the Community of Madrid.

OBJECTIVE: Various studies have identified factors associated with risk of mortality in patients with SARS-CoV-2 infection. However, their sample size has often been limited and their results partially contradictory. This study evaluated factors associated with COVID-19 mortality in the population of Madrid over 75 years of age, in infected patients, and in hospitalized patients up to January 2021. PATIENTS AND METHODS: This population-based cohort study analyzed all residents of the Community of Madrid born before January 1, 1945 who were alive as of December 31, 2019. Demographic and clinical data were obtained from primary care electronic medical records (PC-Madrid), data on hospital admissions from the Conjunto Mínimo Básico de Datos (CMBD, Minimum Data Set), and data on mortality from the Índice Nacional de Defunciones (INDEF, National Death Index). Data on SARS-CoV-2 infection, hospitalization, and death were collected from March 1, 2020 to January 31, 2021. RESULTS: A total of 587,603 subjects were included in the cohort. Of them, 41,603 (7.1%) had confirmed SARS-CoV-2 infection, of which 22,362 (53.7% of the infected individuals) were hospitalized and 11,251 (27%) died. Male sex and age were the factors most closely associated with mortality, though many comorbidities also had an influence. The associations were stronger in the analysis of the total population than in the analysis of infected or hospitalized patients. Mortality among hospitalized patients was lower during the second wave (33.4%) than during the first wave (41.2%) of the pandemic. CONCLUSION: Age, sex, and numerous comorbidities are associated with risk of death due to COVID-19. Mortality in hospitalized patients declined notably after the first wave of the pandemic.

Real-world experience of palbociclib and ribociclib: novel oral therapy in metastatic breast cancer.

Background Palbociclib and ribociclib are novel oral agents in hormone receptor-positive metastatic breast cancer. Neutropenia is a common adverse event associated with these treatments and its clinical management often requires regimen changes, such as cycle delays and dose adjustments. Objective To provide a real-world experience of the effectiveness and toxicities associated with these drugs and to evaluate the impact of regimen changes in disease progression. Setting This study was performed at Hospital Universitario La Paz, in Spain. Methods Observational, retrospective study which included hormone receptor-positive metastatic breast cancer patients who initiated treatment with palbociclib or ribociclib between March 1st, 2018 and March 1st, 2019. Main outcome measure The primary effectiveness variable was progression-free survival. Safety evaluation was performed to determine neutropenia-incidence and severity, as well as its clinical management, including dose adjustments and treatment interruptions. Correlations between these regimen changes and effectiveness were also evaluated. Results Sixty-one patients were included, 33 treated with palbociclib and 28 with ribociclib. Palbociclib was mainly used as second line of treatment in the metastatic setting (81.8%) and ribociclib as first line (67.9%). The median progression-free survival was 12.76 months (95% CI 7.5 to not estimable) in palbociclib and not reached in ribociclib. After 12 months, the progression-free survival rate was 51.5% (95% CI 34-69) in palbociclib and 78.6% (95% CI 63-94.1) in ribociclib. Neutropenia was the most common adverse event with an incidence rate of 87.9% in palbociclib and 82.1% in ribociclib. Cycle delays were needed in more than half of the patients treated with palbociclib and ribociclib (63.6% and 64.3%). Dose adjustments were seen in 42.4% and 53.6% of the patients receiving palbociclib and ribociclib, respectively. Regimen changes did not involve statistically significant differences in 12-month PFS rates in the cohort investigated. Conclusion Palbociclib and ribociclib outcomes are comparable to those reached in the phase III trials, PALOMA-3 and MONALEESA-2, respectively, and cannot be compared as they were used in different treatment settings. The toxicity profile is favourable, being neutropenia the most common adverse event, easily managed with regimen changes. Further studies are needed to confirm the observed tendency of no detrimental impact on effectiveness of these regimen changes.

Is it always necessary to perform an axillary lymph node dissection after neoadjuvant chemotherapy for breast cancer?

INTRODUCTION: Recent prospective studies support the feasibility of performing sentinel lymph node biopsy following neoadjuvant chemotherapy in initially fine-needle aspiration cytology or ultrasound-guided biopsy-proven node-positive breast cancer. The main aid is to identify preoperative features that help us predict a complete axillary response to neoadjuvant chemotherapy in these patients and thus select the candidates for sentinel lymph node biopsy post-neoadjuvant chemotherapy to avoid unnecessary axillary lymphadenectomy. MATERIALS AND METHODS: A retrospective observational study with a total of 150 patients, biopsy-proven node-positive breast cancer who underwent neoadjuvant chemotherapy followed by breast surgery and axillary lymphadenectomy were included and retrospectively analysed. A predictive model was generated by a multivariate logistic regression analysis for pathological complete response-dependent variable. RESULTS: The response of the primary lesion to neoadjuvant chemotherapy according to post-treatment magnetic resonance imaging, Her2/neu overexpression and a low estrogen receptor expression are associated with a higher rate of nodal pathologically complete response. The multivariant model generated a receiver operating characteristic curve with an area under the curve of 0.79 and a confidence interval of 0.72-0.87 at a 95% level of significance. CONCLUSIONS: This model could be a helpful tool for the surgeon to help in predicting which cases have a higher likelihood of achieving a pathologically complete response and therefore selecting those who may benefit from a post-neoadjuvant chemotherapy sentinel lymph node biopsy and avoid unnecessary axillary lymphadenectomy.