The effect of 1-hydroxy-vitamin D treatment in hospitalized patients with COVID-19: A retrospective study.

BACKGROUND & AIMS: The efficacy of vitamin D supplementation in coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to evaluate the effect of 1-hydroxy-vitamin D on the prevention of severe disease and mortality in patients hospitalized for COVID-19. METHODS: This retrospective study included 312 patients with COVID-19 who were admitted to our hospital between April 2021 and October 2021 (primarily the Delta variant) and between July 2022 and September 2022 (primarily Omicron variant). Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at the time of admission and 1-hydroxy-vitamin D was prescribed by the treating physicians. The patients were divided into two groups: those administered 1-hydroxy-vitamin D (Vit D group) and those who were not (control group). The composite primary endpoint was the need for additional respiratory support, including high-flow oxygen therapy or invasive mechanical ventilation, and in-hospital mortality rate. RESULTS: Of 312 patients, 122 (39%) received 1-hydroxy-vitamin D treatment. Although the median age was not significantly higher in the Vit D group than in the control group (66 vs. 58 years old, P = 0.06) and there was no significant difference in the proportion of vitamin D deficiency (defined as serum 25(OH)D level less than 20 ng/mL, 77% vs. 65%, P = 0.07), patients in the control group had a more severe baseline profile compared to the Vit D group according to the Japanese disease severity definition for COVID-19 (P = 0.01). The proportion of those requiring more respiratory support and in-hospital mortality was significantly lower in the Vit D group than in the control group (6% vs. 14%, P = 0.01 log-rank test). After propensity score matching, a statistically significant difference in the primary endpoint was observed (P = 0.03 log-rank test). CONCLUSIONS: 1-hydroxy-vitamin treatment may improve outcomes in hospitalized patients with COVID-19, reducing composite outcomes including the need for additional respiratory support and in-hospital mortality.

Long-Term Efficacy of High-Dose Imatinib in Hispanic Patients Without Access to Second-Generation Tyrosine Kinase Inhibitors Treated in LATAM Centers.

BACKGROUND: While second-generation tyrosine kinase inhibitors (TKI) revolutionized treatment for patients with chronic myeloid leukemia (CML) who developed a suboptimal response to imatinib, many patients in developing countries are fixed to the latter due to socioeconomic barriers. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients. METHODS: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to a standard dose of imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights. Our primary outcome was overall survival (OS) at 150 months. Our secondary outcomes were disease-free survival (DFS) at 150 months and adverse events. RESULTS: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. No difference was found in the 150-month overall survival risk (RR: 95% CI 0.91, 0.55-1.95, P-value = .77; RD: -0.04, -0.3 to 0.21, P-value = .78) and disease-free survival (RR: 1.02, 95% CI 0.53-2.71, P-value = .96; RD: 0.01, -0.26 to 0.22, P-value = .96). There was also no difference in the incidence of adverse events in either group. CONCLUSION: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. If impossible, however, our findings suggest that patients treated with high-dose imatinib have a similar overall survival and disease-free survival prognosis to patients receiving a second-generation TKI.

Violation of the Constant Genetic Effect Assumption Can Result in Biased Estimates for Non-Linear Mendelian Randomization.

INTRODUCTION: Non-linear Mendelian randomization is an extension of conventional Mendelian randomization that performs separate instrumental variable analyses in strata of the study population with different average levels of the exposure. The approach estimates a localized average causal effect function, representing the average causal effect of the exposure on the outcome at different levels of the exposure. The commonly used residual method for dividing the population into strata works under the assumption that the effect of the genetic instrument on the exposure is linear and constant in the study population. However, this assumption may not hold in practice. METHODS: We use the recently developed doubly ranked method to re-analyse various datasets previously analysed using the residual method. In particular, we consider a genetic score for 25-hydroxyvitamin D (25[OH]D) used in a recent non-linear Mendelian randomization analysis to assess the potential effect of vitamin D supplementation on all-cause mortality. RESULTS: The effect of the genetic score on 25(OH)D concentrations varies strongly, with a five-fold difference in the estimated genetic association with the exposure in the lowest and highest decile groups. Evidence for a protective causal effect of vitamin D supplementation on all-cause mortality in low vitamin D individuals is evident for the residual method but not for the doubly ranked method. We show that the constant genetic effect assumption is more reasonable for some exposures and less reasonable for others. If the doubly ranked method indicates that this assumption is violated, then estimates from both the residual and doubly ranked methods can be biased, although bias was smaller on average in the doubly ranked method. CONCLUSION: Analysts wanting to perform non-linear Mendelian randomization should compare results from both the residual and doubly ranked methods, as well as consider transforming the exposure for the residual method to reduce heterogeneity in the genetic effect on the exposure.

Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

Outcomes in breast cancer-does ethnicity matter?

Ethnic or racial differences in breast cancer (BC) survival outcomes have been reported, but current data are largely restricted to comparisons between African Americans and non-Hispanic whites. Most analyses have traditionally been based on self-reported race which may not always be accurate, or are oversimplified in their classification. With increasing globalization, quantification of the genetic ancestry from genomic data may offer a solution to infer the complex makeup from admixture of races. Focusing on the larger and the latest studies, we will discuss recent findings on the differing host and tumor biology that may be driving these disparities, in addition to the extrinsic environmental or lifestyle factors. Socioeconomic disparities with lower cancer literacy may lead to late presentation, poorer adherence to treatment, and other lifestyle factors such as unhealthy diet, obesity, and inadequate physical activity. These hardships may also result in greater allostatic load, which is in turn associated with aggressive BC features in disadvantaged populations. Epigenetic reprogramming may mediate the effects of the environment or lifestyle factors on gene expression, with ensuing differences in BC characteristics and outcome. There is increasing evidence that germline genetics can influence somatic gene alterations or expression, as well as modulate the tumor or immune microenvironment. Although the precise mechanisms remain elusive, this may account for the varying distribution of different BC subtypes across ethnicities. These gaps in our knowledge highlight the need to interrogate the multiomics landscape of BC in diverse populations, ideally in large-scale collaborative settings with standardized methodology for the comparisons to be statistically robust. Together with improving BC awareness and access to good quality health care, a holistic approach with insights of the biological underpinnings is much needed to eradicate ethnic disparities in BC outcomes.

Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Integrating On-Treatment Modified Glasgow Prognostic Score and Imaging to Predict Response and Outcomes in Metastatic Renal Cell Carcinoma.

Importance: In the era of immuno-oncology, imaging alone seems to be insufficient to capture treatment responses, as patients with stable disease treated with immunotherapy have a wide range of clinical outcomes. There is an unmet need for complementary (ideally cost-efficient) markers that enable assessment of therapy response and outcomes in conjunction with imaging. Objectives: To examine whether longitudinal changes in the modified Glasgow prognostic score (mGPS), which is based on C-reactive protein and albumin, can predict responses and outcomes in patients with metastatic renal cell carcinoma (mRCC). Design, Setting, and Participants: This post hoc analysis, conducted from October 2022 to April 2023, evaluated the prognostic and predictive performance of on-treatment mGPS in patients with mRCC being treated with atezolizumab (plus bevacizumab) or sunitinib in 2 randomized clinical trials: the phase 3 IMmotion151 study (discovery cohort) and the phase 2 IMmotion150 study (validation cohort). Main Outcomes and Measures: Outcomes were investigator-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and overall survival (OS) for survival analyses. To compare the prognostic value of the on-treatment mGPS with radiologic staging, we used RECIST assessed by the Independent Review Committee (IRC-RECIST) to ensure high data quality. Results: Of the 915 patients with mRCC in the IMmotion151 discovery cohort, baseline mGPS was available for 861 patients and on-treatment mGPS for 691. The IMmotion150 validation cohort included 305 patients with mRCC, and on-treatment mGPS could be evaluated for 199. In the IMmotion150 study, on-treatment mGPS predicted outcomes as early as 6 weeks following therapy initiation, thereby opening a window for early therapy adjustments. In both clinical trials, on-treatment mGPS provided valuable prognostic information regardless of imaging-assessed treatment response at first staging. Of note, in the disease control subgroup, on-treatment mGPS exhibited superior and independent prognostic information compared with IRC-RECIST (available for 611 patients; C-index, 0.651 [95% CI, 0.588-0.714] for the mGPS during treatment vs 0.574 [95% CI, 0.528-0.619] for IRC-RECIST). Conclusions and Relevance: These data support the concept of integrating on-treatment mGPS for more holistic and patient-centered therapy monitoring in addition to radiologic staging to improve clinical care at a low cost for patients with mRCC.

Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

A retrospective analysis of secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in patients with recurrent ovarian cancer.

AIM: To evaluate the effect of secondary cytoreductive surgery (SeCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer patients. METHODS: This retrospective study analyzed a prospective database. We collected information of 389 patients who were diagnosed with recurrent epithelial ovarian cancer. All patients underwent SeCRS with or without HIPEC. Overall survival and progression-free survival (PFS) were used to evaluate the treatment effectiveness. RESULTS: Of the 389 patients collected, 123 underwent primary or interval cytoreductive surgery at initial treatment and SeCRS at recurrence (Group A), 130 underwent primary or interval cytoreductive surgery at initial and SeCRS plus HIPEC at recurrence (Group B), and 136 underwent primary or interval cytoreductive surgery plus HIPEC at initial and SeCRS plus HIPEC at recurrence (Group C). The median overall survival for Groups A, B, and C were 49.1 months (95% confidence interval [CI]: 47.6-50.5), 56.0 months (95% CI: 54.2-57.7), and 64.4 months (95% CI: 63.1-65.6), respectively. The median PFS for Groups A, B, and C were 13.1 months (95% CI: 12.6-13.5), 15.0 months (95% CI: 14.2-15.7), and 16.8 months (95% CI: 16.1-17.4), respectively. There were no significant difference in incidence and grade of adverse events among groups. CONCLUSIONS: This study suggested that SeCRS plus HIPEC followed by chemotherapy resulted in longer overall survival and PFS than only SeCRS followed by chemotherapy in patients with recurrent ovarian cancer, especially in patients who were treated with repeat HIPEC.

Impact of skeletal muscle volume on patients with BCLC stage-B hepatocellular carcinoma undergoing sorafenib therapy.

AIM: Skeletal muscle volume has been reported to be an important factor that determines overall survival (OS) and post-progression survival (PPS) in patients with hepatocellular carcinoma (HCC). However, the impact of skeletal muscle volume on HCC with Barcelona Clinic Liver Cancer (BCLC) stage B (BCLC-B) remains unclear. We conducted sub-analyses of a previous study on BCLC-B and compared our findings with data on HCC with BCLC stage C (BCLC-C). METHODS: We retrospectively enrolled 356 patients with HCC (BCLC-B, n = 78; and BCLC-C, n = 278) undergoing sorafenib therapy. Prognostic factors were analyzed using various parameters, including skeletal muscle volume. Muscle volume (MV) depletion was designated as less than the median value of the skeletal muscle index for each gender (cutoff value: 45.0 cm2 /m2 for male and 38.0 cm2 /m2 for female participants). RESULTS: Both OS and PPS showed no significant differences in patients with non-MV depletion and those with MV depletion in the BCLC-B group (Median OS [MST] 19.3 vs. 13.5 months [p = 0.348]; median PPS 9.7 vs. 10.8 months [p = 0.578]). In the BCLC-C group, patients with non-MV depletion had a significantly longer OS and PPS compared to patients with MV depletion (MST 12.4 vs. 9.0 months [p = 0.001] and median PPS 7.9 vs. 5.4 months [p = 0.002]). Multivariate analysis revealed that MV depletion was an independent prognostic factor of OS and PPS in the BCLC-C group but not in the BCLC-B group. CONCLUSIONS: Skeletal muscle volume showed little impact on the clinical outcomes of patients with BCLC-B undergoing sorafenib therapy.

Dietary Fats and All-cause and Breast Cancer-specific Mortality among Women with Breast Cancer: The Western New York Exposures and Breast Cancer Study.

BACKGROUND: Study results of prediagnostic dietary fat intake and breast cancer mortality have been inconclusive. While dietary fat subtypes [saturated (SFA), polyunsaturated (PUFA), and monounsaturated (MUFA) fatty acids] may have different biological effects, there is little evidence regarding the association of dietary fat and fat subtype intake with mortality after breast cancer diagnosis. METHODS: Women with incident, pathologically confirmed invasive breast cancer and complete dietary data (n = 793) were followed in a population-based study, the Western New York Exposures and Breast Cancer study. Usual intake before diagnosis of total fat and subtypes were estimated from a food frequency questionnaire completed at baseline. HRs and 95% confidence intervals (CI) for all-cause and breast cancer-specific mortality were estimated with Cox proportional hazards models. Interactions by menopausal status, estrogen receptor (ER) status, and tumor stage were examined. RESULTS: Median follow-up time was 18.75 years; 327 (41.2%) participants had died. Compared with lower intake, greater intake of total fat (HR, 1.05; 95% CI, 0.65-1.70), SFA (1.31; 0.82-2.10), MUFA (0.99; 0.61-1.60), and PUFA (0.99; 0.56-1.75) was not associated with breast cancer-specific mortality. There was also no association with all-cause mortality. Results did not vary by menopausal status, ER status, or tumor stage. CONCLUSIONS: Prediagnostic intake of dietary fat and fat subtypes was not associated with either all-cause or breast cancer mortality in a population-based cohort of breast cancer survivors. IMPACT: Understanding factors affecting survival among women diagnosed with breast cancer is critically important. Dietary fat intake prior to diagnosis may not impact that survival.

Atención integral por cuidados paliativos para pacientes con ventilación mecánica asistida SARS-CoV-2 severos y sus beneficios / Comprehensive care for palliative care for patients with severe SARS-CoV-2 assisted mechanical ventilation and its benefits

Resumen Objetivo. Esta investigación tiene como objetivo describir la población atendida y los beneficios del programa "Lineamiento de atención integral por Cuidados Paliativos en el Área de Salud de Palmares, para pacientes con SARS-CoV-2 severo" con ventilación mecánica asistida, hospitalizados en unidades de cuidados intensivos de la Caja Costarricense del Seguro Social durante la pandemia en Costa Rica, del 10 de junio al 31 de octubre del 2021. Métodos. Estudio descriptivo mixto de la población y los beneficios del programa por medio de indicadores cuantitativos obtenidos del informe de aplicación y cualitativos a través de la realización de una encuesta de satisfacción a usuarios en el período de estudio. Resultados. El programa atendió a 13 pacientes, brindó apoyo en manejo del duelo a los familiares de cinco pacientes que ya habían fallecido y a los cuidadores de ocho pacientes hospitalizados, también ofreció 70 consultas médicas en un período promedio de 62 días. La edad promedio de los pacientes fue de 55 años; doce pacientes presentaban algún factor de riesgo, siendo la obesidad y la falta de esquema de vacunación completo (dos dosis) los más frecuentes. Durante la implementación del programa fallecieron cinco pacientes más, obteniendo una tasa de mortalidad del 78%. A los pacientes que sobrevivieron se les atendió en promedio por 135 días. Con el apoyo del equipo, los pacientes lograron la recuperación clínica de las complicaciones respiratorias y funcionales. Lograron independencia total de actividades básicas de la vida diaria y reinserción social en menos de tres meses después del alta hospitalaria. En general, se documentó una percepción positiva del programa en el 100% de los usuarios, con cambios en el nivel de sufrimiento manifestado por las familias y el apoyo en el manejo del duelo. Conclusión. Con la optimización de uso de los recursos ya existentes en la Caja Costarricense del Seguro Social y la participación social, este programa abordó aspectos no atendidos previamente para los pacientes que sufrieron COVID 19 severo, como el manejo del sufrimiento y/o duelo durante la hospitalización y al egreso. Además, el programa colaboró en la recuperación clínica y funcional de los usuarios sobrevivientes y documentó múltiples beneficios percibidos por el paciente, sus familias, la institución y la sociedad, como el abordaje del sufrimiento, la adecuada atención al duelo, la organización de los recursos asistenciales y la pronta recuperación física, emocional y social del paciente sobreviviente.

Abstract Aim. This research aims to describe the population served and the benefits of the program "Guidelines for integral care for patients with severe SARS-CoV-2 by Palliative Care at the Area de Salud de Palmares " to patients with assisted mechanical ventilation, hospitalized in intensive care units of the Caja Costarricense del Seguro Social during the pandemic in Costa Rica, from June 10 to October 31, 2021. Methods. This study is a mixed descriptive investigation that analyzes quantitative indicators from the report on the program's application and qualitative indicators from a satisfaction survey for the users in the study period. Results. The program treated 13 patients, provided grief management support to the relatives of five patients who had already died and to the caregivers of eight hospitalized patients, and offered 70 medical consultations in an average period of 62 days. The average age of the patients was 55 years; twelve patients had some risk factors, and obesity and lack of a complete vaccination schedule (two doses) were the most frequent. During the program implementation, five more patients died, obtaining a mortality rate of 78%. The average treatment day for surviving patients was 135 days. Through the team's support, patients accomplished clinical recovery from respiratory and functional complications. They got independent basics activities of daily living and social reintegration in less tan three months after discharge. A positive perception of the program was documented in 100% of the program's users, with changes in the level of suffering manifested by the families and the support in grief management. Conclusion. With the optimization of the use of existing resources in the the Caja Costarricense del Seguro Social and the social participation, this program addressed aspects not previously attended to patients who suffered severe COVID 19, such as the management of suffering and/or grief during hospitalization and upon discharge. In addition, the program helped in the clinical and functional recovery of the surviving users, and documented multiple benefits perceived by the patient, their families, the institution, and society, such as the approach to suffering, adequate bereavement care, organization of care resources, and early physical, emotional and social recovery of the survivor patient.

Effect of omega-3 fatty acid use on sepsis and mortality in patients with Covid-19.

Background: This study aimed to investigate the effects of omega-3 fatty acid use on sepsis and mortality in patients treated for COVID-19 disease in the intensive care unit (ICU) based on clinical and laboratory results. Aim: To determine the effect of omega-3 fatty acid use on sepsis and mortality in patients with COVID-19. Patients and Methods: A total of 80 patients with confirmed COVID-19 infection who were hospitalized in the ICU of Ankara City Hospital, received (n = 40) or did not receive (n = 40) omega-3 fatty acid dietary supplementation, were included in this single-center, retrospective study. The clinical and laboratory data of eligible patients were extracted from the hospital records. Results: The mean age was 65.5 (13.6). The mean length of stay in the intensive care unit was 11.5 (6.3) days. Mortality and sepsis development rates were similar in the groups. The frequency of patients who received pulse steroid therapy was higher in the group of patients who did not receive omega-3 (P < 0.05). Hypertension was more common in the patient group receiving omega-3 supplements (P < 0.05). Mean procalcitonin and interleukin-6 (IL-6) levels were significantly lower in patients who received omega-3 supplements compared to those who did not receive supplements (P < 0.001 and P < 0.05). Mean prothrombin time (PT) was shorter in patients receiving omega-3 supplementation (P < 0.05). Conclusions: Study results obtained in this study indicate that providing omega-3 fatty acid supplements may be beneficial to patients with severe COVID-19, however further research with large-scale randomized controlled trials is necessary.

Patterns of adolescent perceived social support and inflammation in adulthood within major racial groups: Findings from a longitudinal, nationally representative sample.

Inflammation, the body's protective response to injury and infection, plays a critical role in physical and mental health outcomes. Elevated chronic inflammation is implicated as a predictor of disease and all-cause mortality and is linked with several psychological disorders. Given that social support is associated with lower rates of mortality and psychopathology, the links between inflammation and social support are well-studied. However, there are many significant gaps related to both the specificity and generalizability of extant findings. There is a paucity of research on the association between social support and inflammation within different racial groups. Additionally, more research is warranted to understand whether social support from different sources uniquely contributes to inflammation, above and beyond other sources of support. Thus, the current study examined whether perceived emotional social support during adolescence predicted inflammation during adulthood within several racial groups. Participants (n = 3,390) were drawn from the National Longitudinal Study of Adolescent to Adult Health (Add Health), identified as either Asian, Black, Latinx, White, or Multiracial, and had complete data on study variables. Consistent with our hypotheses and previous research, greater perceived support during adolescence was associated with lower inflammation during adulthood, but only for White participants. Contrastingly, greater perceived support during adolescence was associated with higher inflammation during adulthood for individuals who identified as Asian, Latinx, Black, or Multiracial. Furthermore, patterns of social support and inflammation within each racial group varied by relationship type. These results highlight the importance of studying relationship processes and health outcomes within racial groups to understand their unique, lived experiences.

Survival Disparities in US Black Compared to White Women with Hormone Receptor Positive-HER2 Negative Breast Cancer.

Black women in the US have significantly higher breast cancer mortality than White women. Within biomarker-defined tumor subtypes, disparate outcomes seem to be limited to women with hormone receptor positive and HER2 negative (HR+/HER2-) breast cancer, a subtype usually associated with favorable prognosis. In this review, we present data from an array of studies that demonstrate significantly higher mortality in Black compared to White women with HR+/HER2-breast cancer and contrast these data to studies from integrated healthcare systems that failed to find survival differences. Then, we describe factors, both biological and non-biological, that may contribute to disparate survival in Black women.

Effectiveness of COVID-19 vaccines on hospitalization and death in Guilan, Iran: a test-negative case-control study.

OBJECTIVES: The present study was conducted to estimate the effectiveness of (BBIBP)-CorV (Sinopharm), ChAdOx1-S/nCoV-19 (AZD1222, Oxford-AstraZeneca), rAd26-rAd5 (Gam-COVID-Vac, Sputnik V), and BIV1-CovIran (COVIran Barekat) and BBV152 COVAXIN (Bharat Biotech) vaccines against hospitalization and death of COVID-19 in Guilan Province of Iran from May 22 to December 21, 2021. METHODS: This test-negative case-control study was conducted on the population aged 5 years and above by extracting information from local databases (The Medical Care Monitoring Center and The Integrated Health System). A logistic regression analysis was performed to estimate the effectiveness of the vaccines against COVID-19 hospitalization and death. RESULTS: The total study population was 42,084, including 19,500 cases (with a positive Reverse Transcriptase-Polymerase Chain Reaction test admitted to hospitals in Guilan Province) and 22,586 controls (with a negative Reverse Transcriptase-Polymerase Chain Reaction test). Among the admitted patients, 1887 deaths occurred. The maximum effectiveness of BBIBP-CorV (Sinopharm) in preventing temporary hospitalization and regular hospitalization was observed 151 days after receiving the second dose, 95% (95% CI: 67-99.4%) and 85% (95% CI: 77-91%) respectively. The maximum effectiveness of the BBIBP-CorV (Sinopharm) vaccine 91-120 days after receiving the second dose against death was showed 56% (95% CI: 33-71%). The maximum effectiveness of ChAdOx1-S/nCoV-19 (AZD1222, Oxford-AstraZeneca) and BIV1-CovIran (COVIran Barekat) in preventing regular hospitalization and death was observed 121-150 and 61-90 days (respectively) after receiving the second dose, reaching 98% (95% CI: 94-99%) and 92% (95% CI: 48-99%), respectively for ChAdOx1-S/nCoV-19 and 95% (95% CI: 91-97%) and 89% (95% CI: 55-98%) respectively, for BIV1-CovIran. CONCLUSION: For almost all vaccines, the study observed an increase in effectiveness against hospitalization and death over time.

Treatment of Hypertension: A Review.

Importance: Hypertension, defined as persistent systolic blood pressure (SBP) at least 130 mm Hg or diastolic BP (DBP) at least 80 mm Hg, affects approximately 116 million adults in the US and more than 1 billion adults worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (coronary heart disease, heart failure, and stroke) and death. Observations: First-line therapy for hypertension is lifestyle modification, including weight loss, healthy dietary pattern that includes low sodium and high potassium intake, physical activity, and moderation or elimination of alcohol consumption. The BP-lowering effects of individual lifestyle components are partially additive and enhance the efficacy of pharmacologic therapy. The decision to initiate antihypertensive medication should be based on the level of BP and the presence of high atherosclerotic CVD risk. First-line drug therapy for hypertension consists of a thiazide or thiazidelike diuretic such as hydrochlorothiazide or chlorthalidone, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker such as enalapril or candesartan, and a calcium channel blocker such as amlodipine and should be titrated according to office and home SBP/DBP levels to achieve in most people an SBP/DBP target (<130/80 mm Hg for adults <65 years and SBP <130 mm Hg in adults ≥65 years). Randomized clinical trials have established the efficacy of BP lowering to reduce the risk of CVD morbidity and mortality. An SBP reduction of 10 mm Hg decreases risk of CVD events by approximately 20% to 30%. Despite the benefits of BP control, only 44% of US adults with hypertension have their SBP/DBP controlled to less than 140/90 mm Hg. Conclusions and Relevance: Hypertension affects approximately 116 million adults in the US and more than 1 billion adults worldwide and is a leading cause of CVD morbidity and mortality. First-line therapy for hypertension is lifestyle modification, consisting of weight loss, dietary sodium reduction and potassium supplementation, healthy dietary pattern, physical activity, and limited alcohol consumption. When drug therapy is required, first-line therapies are thiazide or thiazidelike diuretics, angiotensin-converting enzyme inhibitor or angiotensin receptor blockers, and calcium channel blockers.

Consumption of coffee and tea with all-cause and cause-specific mortality: a prospective cohort study.

BACKGROUND: Previous studies suggested that moderate coffee and tea consumption are associated with lower risk of mortality. However, the association between the combination of coffee and tea consumption with the risk of mortality remains unclear. This study aimed to evaluate the separate and combined associations of coffee and tea consumption with all-cause and cause-specific mortality. METHODS: This prospective cohort study included 498,158 participants (37-73 years) from the UK Biobank between 2006 and 2010. Coffee and tea consumption were assessed at baseline using a self-reported questionnaire. All-cause and cause-specific mortalities, including cardiovascular disease (CVD), respiratory disease, and digestive disease mortality, were obtained from the national death registries. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 12.1 years, 34,699 deaths were identified. The associations of coffee and tea consumption with all-cause and cause-specific mortality attributable to CVD, respiratory disease, and digestive disease were nonlinear (all P nonlinear < 0.001). The association between separate coffee consumption and the risk of all-cause mortality was J-shaped, whereas that of separate tea consumption was reverse J-shaped. Drinking one cup of coffee or three cups of tea per day seemed to link with the lowest risk of mortality. In joint analyses, compared to neither coffee nor tea consumption, the combination of < 1-2 cups/day of coffee and 2-4 cups/day of tea had lower mortality risks for all-cause (HR, 0.78; 95% CI: 0.73-0.85), CVD (HR, 0.76; 95% CI: 0.64-0.91), and respiratory disease (HR, 0.69; 95% CI: 0.57-0.83) mortality. Nevertheless, the lowest HR (95% CI) of drinking both < 1-2 cup/day of coffee and ≥ 5 cups/day of tea for digestive disease mortality was 0.42 (0.34-0.53). CONCLUSIONS: In this large prospective study, separate and combined coffee and tea consumption were inversely associated with all-cause and cause-specific mortality.

[Vitamin D and polymorphisms of VDR and GC genes in the severity and mortality from COVID-19. A systematic review]. / Vitamina D y polimorfismos de los genes VDR y GC en la severidad y mortalidad por COVID-19. Una revisión sistemática.

Introduction: Previous studies have pointed to a possible relationship between vitamin D deficiency and the severity of the disease promoted by SARS-CoV-2, reducing respiratory and cardiovascular complications caused by a hyperreaction of the immune system known as "cytokine storm". This vitamin exerts multiple functions that depend on the presence and levels of different proteins, such as the vitamin D receptor (VDR) and the vitamin D binding protein (DBP), and the existence of single nucleotide polymorphisms (SNPs) of the genes that encode these proteins. The objective of this review is to assess whether some VDR and GC SNPs are risk factors for the most severe forms of COVID-19 disease and whether they condition the response to vitamin D supplementation. A search was performed in PubMed, Google Scholar and Scielo, finding that genotypes in patients affected by COVID-19, were rarely performed, although some studies find a relationship between different alleles and the severity of the disease. The ApaI polymorphism of the VDR gene stands out, as the minor allele "a" increases the risk of mortality from COVID-19 (OR = 11.828, CI: 2,493-56,104, p = 0.002). Results divergency in the efficacy of vitamin D supplementation suggest the need for a larger number of studies. In conclusion, the study of VDR and GC polymorphisms seems essential to effectively treat vitamin D deficiency and particularly to protect against COVID-19. Well-designed studies are needed to elucidate whether plasma vitamin D levels play a role of casuality or causality.

Introducción: Estudios previos han señalado una posible relación entre la deficiencia de la vitamina D y la severidad de la enfermedad promovida por el SARS-CoV-2, reduciendo las complicaciones respiratorias y cardiovasculares causadas por una respuesta exacerbada del sistema inmune. Esta vitamina ejerce múltiples funciones que dependen de la presencia y niveles de diferentes proteínas, como el receptor de la vitamina D (VDR) y la proteína de unión de la vitamina D (DBP), y de la existencia de polimorfismos de un solo nucleótido (SNP) de los genes que codifican a estas proteínas. El objetivo de esta revisión es evaluar si algunos SNP de VDR y GC son factores de riesgo de las formas más severas de la enfermedad COVID-19 y si condicionan la respuesta a la suplementación con vitamina D. Se realizó una búsqueda en PubMed, Google Scholar y Scielo, encontrándose que son escasos los genotipados en pacientes afectados por COVID-19, aunque algunos trabajos hallan una relación entre diferentes alelos y la severidad de la enfermedad. Destaca el polimorfismo ApaI del gen VDR, el cual alelo menor "a" aumenta el riesgo de mortalidad por COVID-19 (OR = 11,828, CI: 2.493-56.104, p = 0,002). La divergencia de resultados en la eficacia de la suplementación de vitamina D sugiere la necesidad de un mayor número de estudios. En conclusión, el estudio de polimorfismos VDR y GC resulta fundamental para tratar eficazmente la deficiencia de vitamina D y en particular en la protección frente a COVID-19. Se necesitan estudios bien diseñados para dilucidar si los niveles plasmáticos de vitamina D juegan un papel de casualidad o causalidad.