Validity of bioelectric impedance analysis for body composition assessment in interstitial lung disease patients.

BACKGROUND: changes in body composition (BC) are common in interstitial lung disease, which leads to an increased risk of complications and infections, and are associated with poor quality of life and worse outcomes. BC assessment is important to identify malnutrition and sarcopenia. However, gold-standard techniques are not available in all clinical settings. AIMS: this study aimed to evaluate the agreement and reliability of body composition estimated by bioelectric impedance analysis (BIA) and measured using dual-energy x-ray absorptiometry (DEXA) in women with interstitial lung disease. METHODS: this is a cross-sectional study. BC (fat mass and appendicular skeletal muscle mass) were assessed using BIA multifrequency and DEXA in standardized conditions. Agreement and reliability between techniques were evaluated using Bland-Altman plots and the intraclass correlation coefficient (ICC). RESULTS: a total of 50 women were evaluated. No differences were observed for FM (BIA, 25.8 ± 10.2 kg and DEXA, 26.3 ± 10.0 kg, p = 0.77) and ASMM (BIA, 14.1 ± 2.7 kg and DEXA, 13.9 ± 2.3 kg, p = 0.83). Based on ICC, good reliability was observed for FM (ICC, 0.98) and ASMM (ICC, 0.93). CONCLUSION: BC estimated by BIA showed good agreement and reliability with DEXA measurements. In the absence of this method, BIA can replace the DEXA technique for body composition assessment.

Fluid Status Assessment in Critically Ill Patients with COVID-19: A Retrospective Cohort Study.

Fluid status (FS) is a diagnostic challenge in critically ill patients with COVID-19. Here, we compared parameters related to FS derived from cumulative fluid balance (CFB), bioelectrical impedance analysis (BIA) and venous congestion assessed by ultrasound (VExUS) to predict mortality. We retrospectively reviewed the medical records of individuals with severe pneumonia due to COVID-19 between July and November 2021 in a single center. Comorbidities, demographic, clinical and laboratory data as well as results from CFB, BIA and VExUS measurements were collected on admission and weekly afterwards for two consecutive evaluations. Seventy-nine patients were included, of which eighteen (14.2%) died. Abnormalities of FS were only identified by BIA. Extracellular water/total body water ratio (ECW/TBW) > 0.394 (overhydrated) by BIA was a good predictor of mortality (AUC = 0.78, 95% CI: 0.067-0.89). Mortality risk was higher in overhydrated patients (OR: 6.2, 95% CI: 1.2-32.6, p = 0.02) and in persistently overhydrated patients (OR: 9.57, 95% CI: 1.18-77.5, p = 0.03) even after adjustment to age, serum albumin and acute kidney injury (AKI) in stages 2-3. Time to death was shorter in overhydrated patients (HR: 2.82, 95% CI: 1.05-7.5, log-rank test p = 0.03). Abnormalities in FS associated with mortality were only identified by BIA in critically ill patients with COVID-19.

Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection.

Introduction: Our understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children. Methods: We enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata. Results: Children had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively). Conclusion: The gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.

Changes in pulmonary mechanics from supine to prone position measured through esophageal manometry in critically ill patients with COVID-19 severe acute respiratory distress syndrome.

OBJECTIVE: To describe changes in pulmonary mechanics when changing from supine position (SP) to prone position (PP) in mechanically ventilated (MV) patients with Acute Respiratory Distress Syndrome (ARDS) due to severe COVID-19. DESIGN: Retrospective cohort. SETTING: Intensive Care Unit of the National Institute of Respiratory Diseases (Mexico City). PATIENTS: COVID-19 patients on MV due to ARDS, with criteria for PP. INTERVENTION: Measurement of pulmonary mechanics in patients on SP to PP, using esophageal manometry. MAIN VARIABLES OF INTEREST: Changes in lung and thoracic wall mechanics in SP and PP RESULTS: Nineteen patients were included. Changes during first prone positioning were reported. Reductions in lung stress (10.6 vs 7.7, p=0.02), lung strain (0.74 vs 0.57, p=0.02), lung elastance (p=0.01), chest wall elastance (p=0.003) and relation of respiratory system elastances (p=0.001) were observed between patients when changing from SP to PP. No differences were observed in driving pressure (p=0.19) and transpulmonary pressure during inspiration (p=0.70). CONCLUSIONS: Changes in pulmonary mechanics were observed when patients were comparing values of supine position with measurements obtained 24h after prone positioning. Esophageal pressure monitoring may facilitate ventilator management despite patient positioning.

Feeding intolerance during prolonged prone position in overweight and obese patients with severe COVID-19.

Introduction: Objective: the aim of this study was to compare the incidence rate of feeding intolerance (FI) during supine (SP) or prone positioning (PP) in critically ill COVID-19 patients. Methods: this was a retrospective cohort study of critically ill patients with overweight or obesity who received enteral nutrition (EN) in prone or supine positioning continuously during the first five days of mechanical ventilation. Nutritional risk, anthropometric measurements and body composition were assessed at the first 24 hours upon Intensive Care Unit (ICU) admission. Biochemical and clinical variables (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation II [APACHE II], Acute Kidney Injury [AKI] or comorbidities diagnosis) were collected. Pharmacotherapy (prokinetics, sedatives or neuromuscular blocking agents) and FI incidence (gastric residual volume [GRV] ≥ 200 ml or ≥ 500 ml, vomiting or diarrhea) were daily recorded. Constipation was defined as the absence of evacuation for five consecutive days. Results: eighty-two patients were included. Higher rate of prophylactic prokinetic prescription was observed in PP (42.8 vs 12.5 %, p = 0.002). GRV ≥ 200 in supine position was not different when compared to PP (p = 0.47). Vomiting episodes in supine compared to PP showed no difference between groups (15 % vs 24 %, p = 0.31). No differences in diarrhea events were detected (10 % vs 4.7 %, p = 0.36). Constipation was common in both groups (95 % vs 82 %, p = 0.06). Conclusion: FI during prone position was not different in comparison to supine position. Routinely use of prokinetics in continuous prone position may help to prevent FI incidence. Algorithm development is necessary for FI prevention and treatment so to avoid EN interruptions and adverse clinical outcomes.

Introducción: Objetivo: comparar la incidencia de intolerancia a la alimentación entre pacientes críticos en posición supino (PS) o prono (PP). Métodos: cohorte retrospectiva de pacientes bajo ventilación mecánica por distrés respiratorio por COVID-19 y sobrepeso y obesidad, quienes recibieron nutrición enteral (NE) en PP o PS. Se evaluaron riesgo nutricional, mediciones antropométricas y composición corporal en las primeras 24 horas de ingreso a la Unidad de Cuidados Intensivos (UCI). Se recolectaron variables bioquímicas y clínicas (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation II [APACHE II], lesión renal aguda y otras comorbilidades). Se registró el esquema de farmacoterapia prescrita durante los primeros cinco días (procinéticos, sedantes y bloqueadores neuromusculares). Se evaluó la incidencia de intolerancia a la alimentación, definida como la presencia de residuo gástrico (RG) ≥ 200 o ≥ 500 ml, vómito, diarrea o estreñimiento. Resultados: fueron incluidos 82 pacientes. Se observó una mayor prescripción de procinéticos como terapia profiláctica en PP (42,8 vs. 12,5 %, p = 0,002). No se observaron diferencias en RG ≥ 200 ml (p = 0,47) ni vómito (p = 0,31) entre ambos grupos. No se observaron diferencias en episodios de diarrea (10 % en PS vs. 4,7 % en PP, p = 0,36). El estreñimiento fue común en ambos grupos de estudio (95 vs. 82 %, p = 0,06). Conclusiones: la PP no se relaciona con una mayor incidencia de intolerancias a la alimentación. El uso rutinario de procinéticos durante la PP continua puede ayudar a prevenir la incidencia de dichas intolerancias. Es necesario el desarrollo de algoritmos para la prevención y tratamiento de las intolerancias a la alimentación para evitar interrupciones en la NE y desenlaces no deseables.

Is There a Place for Family-centered Cesarean Delivery during Placenta Accreta Spectrum Treatment? / Existe um lugar para cesariana centrada na família durante o tratamento do espectro da placenta acreta?

ABSTRACT Objective Placenta accreta spectrum (PAS) is a cause of massive obstetric hemorrhage and maternal mortality. The application of family-centered delivery techniques (FCDTs) during surgery to treat this disease is infrequent. We evaluate the implementation of FCDTs during PAS surgeries. Methods This was a prospective, descriptive study that included PAS patients undergoing surgical management over a 12-month period. The patients were divided according to whether FCDTs were applied (group 1) or not (group 2), and the clinical outcomes were measured. In addition, hospital anesthesiologists were surveyed to evaluate their opinions regarding the implementation of FCDTs during the surgical management of PAS. Results Thirteen patients with PAS were included. The implementation of FCDTs during birth was possible in 53.8% of the patients. The presence of a companion during surgery and skin-to-skin contact did not hinder interdisciplinary management in any case. Conclusion Implementation of FCDTs during PAS care is possible in selected patients at centers with experience in managing this disease.

Resumo Objetivo O espectro da placenta acreta (do inglês placenta accreta spectrum - PAS) é causa de hemorragia obstétrica maciça e mortalidade materna. A aplicação de técnicas de parto centrado na família (do inglês family-centered delivery techniques - FCDTs) durante a cirurgia para tratar esta doença é pouco frequente. Avaliamos a implementação das FCDTs durante as cirurgias do PAS. Métodos Estudo prospectivo e descritivo que incluiu pacientes com PAS submetidos a tratamento cirúrgico durante um período de 12 meses. Os pacientes foram divididos de acordo com a aplicação de FCDTs (grupo 1) ou não (grupo 2), e os resultados clínicos foram medidos. Além disso, anestesiologistas hospitalares foram entrevistados para avaliar suas opiniões sobre a implementação das FCDTs durante o manejo cirúrgico do PAS. Resultados Foram incluídos 13 pacientes com PAS. A implementação de FCDTs durante o parto foi possível em 53,8% das pacientes. A presença do acompanhante durante a cirurgia e o contato pele a pele não prejudicou o manejo interdisciplinar em nenhum caso. Conclusão A implementação de FCDTs durante o atendimento do PAS é possível em pacientes selecionados em centros com experiência no manejo dessa doença.

Is There a Place for Family-centered Cesarean Delivery during Placenta Accreta Spectrum Treatment?

OBJECTIVE: Placenta accreta spectrum (PAS) is a cause of massive obstetric hemorrhage and maternal mortality. The application of family-centered delivery techniques (FCDTs) during surgery to treat this disease is infrequent. We evaluate the implementation of FCDTs during PAS surgeries. METHODS: This was a prospective, descriptive study that included PAS patients undergoing surgical management over a 12-month period. The patients were divided according to whether FCDTs were applied (group 1) or not (group 2), and the clinical outcomes were measured. In addition, hospital anesthesiologists were surveyed to evaluate their opinions regarding the implementation of FCDTs during the surgical management of PAS. RESULTS: Thirteen patients with PAS were included. The implementation of FCDTs during birth was possible in 53.8% of the patients. The presence of a companion during surgery and skin-to-skin contact did not hinder interdisciplinary management in any case. CONCLUSION: Implementation of FCDTs during PAS care is possible in selected patients at centers with experience in managing this disease.

OBJETIVO: O espectro da placenta acreta (do inglês placenta accreta spectrum - PAS) é causa de hemorragia obstétrica maciça e mortalidade materna. A aplicação de técnicas de parto centrado na família (do inglês family-centered delivery techniques - FCDTs) durante a cirurgia para tratar esta doença é pouco frequente. Avaliamos a implementação das FCDTs durante as cirurgias do PAS. MéTODOS: Estudo prospectivo e descritivo que incluiu pacientes com PAS submetidos a tratamento cirúrgico durante um período de 12 meses. Os pacientes foram divididos de acordo com a aplicação de FCDTs (grupo 1) ou não (grupo 2), e os resultados clínicos foram medidos. Além disso, anestesiologistas hospitalares foram entrevistados para avaliar suas opiniões sobre a implementação das FCDTs durante o manejo cirúrgico do PAS. RESULTADOS: Foram incluídos 13 pacientes com PAS. A implementação de FCDTs durante o parto foi possível em 53,8% das pacientes. A presença do acompanhante durante a cirurgia e o contato pele a pele não prejudicou o manejo interdisciplinar em nenhum caso. CONCLUSãO: A implementação de FCDTs durante o atendimento do PAS é possível em pacientes selecionados em centros com experiência no manejo dessa doença.

Association between kidney biopsy findings in CKD patients with diabetes and renal replacement therapy initiation, a perspective from a low-middle income country.

Kidney disease in diabetes mellitus is usually explained by diabetic kidney disease, but other superimposed etiologies occur frequently. The distinction between diabetic kidney disease and non-diabetic kidney disease can only be made by performing kidney biopsy. Our objective was to evaluate the association of diabetic kidney disease, non-diabetic kidney disease, or both with renal replacement therapy initiation. This is a retrospective cohort that included patients with type 2 diabetes mellitus for whom a kidney biopsy was indicated. Subjects were followed-up for 5 years, until renal replacement therapy initiation or were lost to follow up. One hundred and forty-one patients were included, 53 (39%) had diabetic kidney disease, 13 (9%) had non-diabetic kidney disease and 75 (54%) had both. Ninety-four percent of the cohort initiated renal replacement therapy during the 5-year follow-up. Higher degree of fibrosis was associated with a trend towards higher risk of requiring renal replacement therapy. In addition, the combined diabetic kidney disease + non-diabetic kidney disease group was associated with higher need of renal replacement therapy initiation when compared to the diabetic kidney disease group.

Phase 1b study of berzosertib and cisplatin in patients with advanced triple-negative breast cancer.

Platinum derivatives are commonly used for the treatment of patients with metastatic triple-negative breast cancer (TNBC). However, resistance often develops, leading to treatment failure. This expansion cohort (part C2) of the previously reported phase 1b trial (NCT02157792) is based on the recommended phase 2 dose of the combination of the ataxia-telangiectasia and Rad3-related (ATR) inhibitor berzosertib and cisplatin observed in patients with advanced solid tumors, including TNBC. Forty-seven patients aged ≥18 years with advanced TNBC received cisplatin (75 mg/m2; day 1) and berzosertib (140 mg/m2; days 2 and 9), in 21-day cycles. Berzosertib was well tolerated, with a similar toxicity profile to that reported previously for this combination. The overall response rate (90% confidence interval) was 23.4% (13.7, 35.8). No relevant associations were observed between response and gene alterations. Further studies combining ATR inhibitors with platinum compounds may be warranted in highly selected patient populations.

Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors.

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM. METHODS: This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors. Fifteen patients received palliative RT (30 Gy in 10 fractions) and escalating doses of M3541 (50-300 mg administered on RT fraction days) guided by a Bayesian 2-parameter logistic regression model with overdose control. RESULTS: Doses of M3541 up to 300 mg/fraction day were well tolerated. One patient (200 mg group) experienced two dose-limiting toxicities (urinary tract infection, febrile neutropenia) that resolved with antibiotics. All patients reported ≥ 1 treatment-emergent adverse event (TEAE) but none led to treatment discontinuation. No grade ≥ 4 TEAEs were reported and there was no indication of a dose effect for any TEAE. Three patients (20.0%; 95% confidence interval 4.3-48.1) had confirmed complete or partial response. M3541 total plasma levels did not increase with dose following single or repeated dosing. No relationship was observed between dose and changes in the ratio of phosphorylated to total ATM or in immune cell counts. CONCLUSIONS: The MTD and RP2D could not be established as the study closed early due to the absence of a dose-response relationship and non-optimal PK profile. No further clinical development of M3541 was pursued. (Trial registration number ClinicalTrials.gov NCT03225105. Registration date July 21, 2017).

Normal weight obesity is associated with hypercholesterolemia and low muscle mass in persons living with HIV on antiretroviral treatment.

OBJECTIVES: Normal weight obesity (NWO) is defined as a condition of normal body weight, but with high body fat percentage. Clinical and immunologic implications of NWO in persons living with HIV (PLHIV) remain unknown. The aim of this study was to examine NWO prevalence and its associations with metabolic and immunologic measurements in a cohort of PLHIV on antiretroviral treatment (ART). METHODS: We enrolled 73 adult PLHIV on ART. Body composition was assessed by dual-energy x-ray absorptiometry. NWO was defined as body mass index 18.5 to 24.9 kg/m2 and body fat ≥25%. We determined triacylglycerols, total cholesterol, high-density lipoprotein, low-density lipoprotein, blood glucose, blood pressure, bone mineral density, inflammatory cytokines (interleukin [IL]-1ß, tumor necrosis factor-α and IL-6) and CD4+ and CD8+ T-cell activation. RESULTS: The prevalence of NWO was 49% (36 of 73). Participants with NWO showed lower CD4+ T-cell percentage (25 versus 27%, P = 0.03), lower CD4/CD8 ratio (0.62 versus 0.82, P = 0.02), lower muscle mass (6.84 versus 7.11 kg/m2, P = 0.01) and higher prevalence of hypercholesterolemia (26% versus 6%, P = 0.03) than individuals with normal body composition. No differences in inflammation/activation markers were observed between groups (P > 0.05 in all cases). CONCLUSION: NWO was frequent in a cohort of Mexican PLHIV on ART and was associated with lower muscle mass, hypercholesterolemia, lower CD4+ T-cell percentage, and lower CD4/CD8 ratio. The incorporation of body fat measurements in the regular physical examination of PLHIV could contribute to early identification of the NWO condition and lead to better management of possible long-term morbidity.

Phase angle and overhydration are associated with post-extubating dysphagia in patients with COVID-19 discharged from the ICU.

BACKGROUND: Few studies have evaluated the prevalence of post-extubation dysphagia and associated factors in patients with coronavirus disease 2019 (COVID-19) . Our study assessed the prevalence of post-extubation dysphagia and body composition in patients with COVID-19 discharged from an intensive care unit (ICU). METHODS: A prospective cohort study was performed in post-ICU extubated patients with acute respiratory distress syndrome related to COVID-19 in two referral hospitals. A total of 112 patients were evaluated and included; swallowing assessment and bioelectrical impedance analysis (BIA) were performed after extubation and discharge from the ICU. To identify associations between dysphagia, lower phase angle (PhA) (<4.8°) and hydration (extracellular water/total body water < 0.390) logistic and linear regression analyses were conducted. RESULTS: The incidence of post-extubation dysphagia was 41% (n = 46). From these, 65% (n = 30) had severe swallowing impairment. Overhydration and PhA were significantly different in patients with dysphagia, and segmental hydration in the trunk and legs was higher than in arms. PhA <4.8° (odds ratio [OR], 12.2; 95% CI, 4.3-34.1; P < .05) and overhydration measured by BIA (OR, 9.1; 95% CI, 3.4-24.5; P < .05) were associated with post-extubation dysphagia in multivariate analysis. PhA (<4.8°) was associated with a lower rate of swallowing recovery at hospital discharge (log-rank test = 0.007). CONCLUSIONS: A high incidence of post-extubation dysphagia was found in patients with COVID-19. Low PhA and overhydration were associated with the presence of dysphagia. Lower PhA was an independent factor for swallowing recovery at discharge.

Phase angle as predictor of malnutrition in people living with HIV/AIDS.

BACKGROUND: Phase angle (PhA), measured by bioelectrical impedance analysis (BIA) has been studied as an indicator of survival in people living with HIV (PLWH). However, it remains unclear whether PhA is associated with malnutrition or low CD4+ T-cell counts. OBJECTIVE: In this study, we assessed the discriminative capacity of PhA for malnutrition detection using Global Leadership Initiative on Malnutrition (GLIM) criteria in PLWH, aiming to propose cutoff points for this population. METHODS: This retrospective observational study included 427 adult PLWH (13% female). Participants were classified according to malnutrition status by using GLIM criteria. Body composition was assessed by using BIA. CD4+ T-cell counts were determined by flow cytometry. RESULTS: According to GLIM criteria, 30% of the participants were malnourished. Multivariate regression analysis showed that PhA (adjusted odds ratio [OR], 0.10; 95% CI, 0.05-0.18; P < 0.001), fat-mass percentage (adjusted OR, 0.86; 95% CI, 0.82-0.90; P < 0.001), and male sex (adjusted OR, 0.26; 95% CI, 0.09-0.76; P = 0.013) were independently associated with malnutrition. A PhA cutoff of 5.45° in men and 4.95° in women may predict malnutrition with sensitivity and specificity >70%. CONCLUSION: PhA could be a valid, useful, and simple predictor of malnutrition in PLWH.

Low phase angle is associated with 60-day mortality in critically ill patients with COVID-19.

BACKGROUND: Malnutrition status, body composition indicators, and bioelectrical impedance analysis (BIA) parameters have been associated with increased risk of death in several pathologies. The aim of this study was to describe the associations between phase angle (PhA) indicators obtained by BIA with length of hospital stay, days on mechanical ventilation, and 60-day mortality in critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a prospective cohort of mechanically ventilated patients with coronavirus disease 2019 (COVID-19). We assessed nutrition risk and body composition with BIA within 48 h from intensive care unit admission. Logistic and linear regression models were used to analyze the association between variables and clinical outcomes. Survival analysis by PhA value was performed using Kaplan-Meier curves. RESULTS: Sixty-seven patients were included. PhA (odds ratio [OR], 0.36; P = .002), standardized PhA (SPA) (OR, 0.45; P = .001), and extracellular water/total body water ratio (OR, 3.25; P = .002) were significant predictors of 60-day mortality. PhA <3.85° in females and <5.25° in males showed good and fair discrimination, respectively, for mortality prediction. Using cutoff values, low PhA was associated with a significantly increased risk of 60-day mortality (hazard ratio, 3.08; 95% CI, 1.12-8.41; P = .02). No association was detected for SPA. CONCLUSION: Low PhA values could be a predictor of 60-day mortality in critically ill patients with COVID-19. This biological marker could be incorporated as part of nutrition and mortality risk assessment in this population.

A phase 1b study evaluating the safety and preliminary efficacy of berzosertib in combination with gemcitabine in patients with advanced non-small cell lung cancer.

OBJECTIVES: Berzosertib (formerly M6620, VX-970) is an intravenous, highly potent and selective, first-in-class ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. We assessed the safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of berzosertib plus gemcitabine in an expansion cohort of patients with advanced non-small cell lung cancer (NSCLC). The association of efficacy with TP53 status and other tumor markers was also explored. MATERIALS AND METHODS: Adult patients with advanced histologically confirmed NSCLC received berzosertib 210 mg/m2 (days 2 and 9) and gemcitabine 1000 mg/m2 (days 1 and 8) at the recommended phase 2 dose established in the dose escalation part of the study. RESULTS: Thirty-eight patients received at least one dose of study treatment. The most common treatment-emergent adverse events were fatigue (55.3%), anemia (52.6%), and nausea (39.5%). Gemcitabine had no apparent effect on the PK of berzosertib. The objective response rate (ORR) was 10.5% (4/38, 90% confidence interval [CI]: 3.7-22.5%). In the exploratory analysis, the ORR was 30.0% (3/10, 90% CI: 9.0-61.0%) in patients with high loss of heterozygosity (LOH) and 11.0% (1/9, 90% CI: 1.0-43.0%) in patients with low LOH. The ORR was 33.0% (2/6, 90% CI: 6.0-73.0%) in patients with high tumor mutational burden (TMB), 12.5% (2/16, 90% CI: 2.0-34.0%) in patients with intermediate TMB, and 0% (0/3, 90% CI: 0.0-53.6%) in patients with low TMB. CONCLUSIONS: Berzosertib plus gemcitabine was well tolerated in patients with advanced, pre-treated NSCLC. Based on the observed clinical efficacy, future clinical trials should involve genomically selected patients.

Fear is the Path to the Dark Side: Unsafe Delivery, One of the Consequences of Fear of the SARS-CoV-2 Pandemic, A Case Report.

Indirect effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are difficult to calculate. Fear of intrahospital infection has led to a decrease in the use of emergency services and the performance of elective procedures. Several low- and middle-income countries have seen the number of institutional deliveries reduced, even in the absence of a follow-up program for home births. We present the case of a patient with adequate prenatal care and an institutional delivery plan who, due to the SARS-CoV-2 pandemic, chose to have a home delivery with unsafe conditions. The lack of supervision by health personnel and the absence of an immediate consultation plan facilitated the presentation of postpartum hemorrhage and poor neonatal results. Little attention has been paid during the pandemic to pregnant women who decide to have their birth at home. A broad discussion is necessary in this regard, to regain the confidence of the population and strengthen institutional births, or to strengthen midwife-assisted home births programs. Patients' fear to acquiring SARS-CoV-2 infection inside hospitals is a factor that must be taken into account in prenatal care programs.