The re-emerging association between tuberculosis and diabetes: lessons from past centuries

The association between tuberculosis (TB) and diabetes mellitus (DM) had a common place in the literature up to the first half of the 20th century, but virtually disappeared with the discovery of insulin to treat DM and antibiotics to cure TB. In the late 1990s the literature began to re-emerge with the worldwide increase in type 2 DM, particularly in TB-endemic countries. Today, type 2 DM is the most prevalent comorbidity among TB patients and the World Health Organization considers it a threat to TB control. We summarize the literature on TB and DM up to the 1960s. Then we evaluate unique aspects of this comorbidity in older times, such as the frequent diabetic comas that suggest challenges for proper DM management as insulin was being implemented, or the absence of antibiotics to cure TB. Despite the unique aspects of each study period, the literature across times is consistent in key aspects of the association. Namely, a higher TB prevalence among DM (versus non-DM patients), the importance of glucose control and chronic DM on TB susceptibility and the higher risk of death among patients with the comorbidity. From the older literature, we can infer the likely contribution of type 1 DM to TB (in addition to type 2), regardless of their differing autoimmune or metabolic pathophysiology, respectively. Furthermore, in the older literature there was a notable reporting of DM development among TB patients, even though DM usually preceded TB. This observation deserves further epidemiological and basic studies to elucidate this intriguing aspect of the relationship between TB and DM

Do Antiplatelet Medications Prevent Poor Clinical Outcomes in Patients With Community-Acquired Pneumonia? Results From the Community-Acquired Pneumonia Organization International Cohort Study

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Correlation of Obesity With Outcomes in Hospitalized Patients With Community-Acquired Pneumonia: Results From the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

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Clinical Characteristics and Outcomes of Patients With Community-Acquired Pneumonia—Real-Life Versus Food and Drug Administration (FDA) Trials: Results From the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

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Using Cluster Analysis of Cytokines to Identify Patterns of Inflammation in Hospitalized Patients with Community-acquired Pneumonia:A Pilot Study

Purpose: Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies. Methods: Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN)γ, tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations. Results: A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum. Conclusions: Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies

A prospective cross-sectional study of tuberculosis in elderly Hispanics reveals that BCG vaccination at birth is protective whereas diabetes is not a risk factor

Background: Aging increases the risk of tuberculosis (TB) and its adverse outcomes, but most studies are based on secondary analyses, and few are in Hispanics. Diabetes is a risk factor for TB in adults, but its contribution in the elderly is unknown. We aimed to identify the role of diabetes and other risk factors for TB in elderly Hispanics. Methods: Cross-sectional study among newly-diagnosed TB patients, recent contacts (ReC), or community controls (CoC) totaling 646 participants, including 183 elderly (\u3e60 years; 43 TB, 80 ReC, 60 CoC) and 463 adults (18 to 50 years; 80 TB, 301 ReC and 82 CoC). Host characteristics associated with TB and latent Mycobacterium tuberculosis infection (LTBI) were identified in the elderly by univariable and confirmed by multivariable logistic regression. Results: LTBI was more prevalent among the elderly CoC (55% vs. 23.2% in adults; p\u3c0.001), but not in ReC (elderly 71.3% vs. adult 63.8%); p = 0.213). Risk factors for TB in the elderly included male sex (adj-OR 4.33, 95% CI 1.76, 10.65), smoking (adj-OR 2.55, 95% CI 1.01, 6.45) and low BMI (adj-OR 12.34, 95% CI 4.44, 34.33). Unexpectedly, type 2 diabetes was not associated with TB despite its high prevalence (adj-OR 0.38, 95% CI 0.06, 2.38), and BCG vaccination at birth was protective (adj-OR 0.16, 95% CI 0.06, 0.45). Conclusions: We report novel distinctions in TB risk factors in the elderly vs. adults, notably in diabetes and BCG vaccination at birth. Further studies are warranted to address disparities in this vulnerable, understudied population

Differential Role of Type 2 Diabetes as a Risk Factor for Tuberculosis in the Elderly versus Younger Adults

The elderly are understudied despite their high risk of tuberculosis (TB). We sought to identify factors underlying the lack of an association between TB and type 2 diabetes (T2D) in the elderly, but not adults. We conducted a case–control study in elderly (≥65 years old; ELD) vs. younger adults (young/middle-aged adults (18–44/45–64 years old; YA|MAA) stratified by TB and T2D, using a research study population (n = 1160) and TB surveillance data (n = 8783). In the research study population the adjusted odds ratio (AOR) of TB in T2D was highest in young adults (AOR 6.48) but waned with age becoming non-significant in the elderly. Findings were validated using TB surveillance data. T2D in the elderly (vs. T2D in younger individuals) was characterized by better glucose control (e.g., lower hyperglycemia or HbA1c), lower insulin resistance, more sulphonylureas use, and features of less inflammation (e.g., lower obesity, neutrophils, platelets, anti-inflammatory use). We posit that differences underlying glucose dysregulation and inflammation in elderly vs. younger adults with T2D, contribute to their differential association with TB. Studies in the elderly provide valuable insights into TB-T2D pathogenesis, e.g., here we identified insulin resistance as a novel candidate mechanism by which T2D may increase active TB risk

Tuberculosis in elderly Hispanics: BCG vaccination at birth is protective whereas diabetes is not a risk factor

Background. Aging increases the risk of tuberculosis (TB) and its adverse outcomes, but most studies are based on secondary analyses, and few are in Hispanics. Diabetes is a risk factor for TB in adults, but its contribution in the elderly is unknown. We aimed to identify the role of diabetes and other risk factors for TB in elderly Hispanics. Methods. Cross-sectional study among newly-diagnosed TB patients, recent contacts (ReC), or community controls (CoC) totaling 646 participants, including 183 elderly (\u3e60 years; 43 TB, 80 ReC, 60 CoC) and 463 adults (18 to 50 years; 80 TB, 301 ReC and 82 CoC). Host characteristics associated with TB and latent Mycobacterium tuberculosis infection (LTBI) were identified in the elderly by univariable and confirmed by multivariable logistic regression. Results. LTBI was more prevalent among the elderly CoC (55% vs. 23.2% in adults; pvs. adult 63.8%); p=0.213). Risk factors for TB in the elderly included male sex (adj-OR 4.33, 95% CI 1.76, 10.65), smoking (adj-OR 2.55, 95% CI 1.01, 6.45) and low BMI (adj-OR 12.34, 95% CI 4.44, 34.33). Unexpectedly, diabetes was not associated with TB despite its high prevalence (adj-OR 0.38, 95% CI 0.06, 2.38), and BCG vaccination at birth was protective (adj-OR 0.16, 95% CI 0.06, 0.45). Conclusions. We report novel distinctions in TB risk factors in the elderly vs. adults, notably in diabetes and BCG vaccination at birth. Further studies are warranted to address disparities in this vulnerable, understudied population

Metabolic Signatures Associated with Severity in Hospitalized COVID-19 Patients

The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic pathways that are altered early with viral infection and their association with disease severity is crucial to understand COVID-19 pathophysiology, and guide clinical decisions. This study aimed at assessing the critical metabolic pathways altered with disease severity in hospitalized COVID-19 patients. Forty-nine hospitalized patients with COVID-19 pneumonia were enrolled in a prospective, observational, single-center study in Barcelona, Spain. Demographic, clinical, and analytical data at admission were registered. Plasma samples were collected within the first 48 h following hospitalization. Patients were stratified based on the severity of their evolution as moderate (N = 13), severe (N = 10), or critical (N = 26). A panel of 221 biomarkers was measured by targeted metabolomics in order to evaluate metabolic changes associated with subsequent disease severity. Our results show that obesity, respiratory rate, blood pressure, and oxygen saturation, as well as some analytical parameters and radiological findings, were all associated with disease severity. Additionally, ceramide metabolism, tryptophan degradation, and reductions in several metabolic reactions involving nicotinamide adenine nucleotide (NAD) at inclusion were significantly associated with respiratory severity and correlated with inflammation. In summary, assessment of the metabolomic profile of COVID-19 patients could assist in disease severity stratification and even in guiding clinical decisions

Beneficios del uso de vitamina C en el paciente séptico: ¿qué tanto la apoya la evidencia esta indicación?

Objetivo: resumir y analizar la evidencia más reciente sobre el efecto de la administración de vitamina C en el paciente con sepsis. Métodos: revisión narrativa. Se realizó una búsqueda bibliográfica, utilizando los términos de búsqueda “Vitamina C” y “Sepsis”, además de sinónimos, los cuales fueron combinados con los operadores “AND” y “OR”, en las bases de datos PubMed, ScienceDirect, Web of Science, y MEDLINE. Resultados: basados en los últimos estudios celulares y moleculares, se ha evidenciado que la vitamina C posee propiedades antioxidantes, antiinflamatorias, y microbicidas, pudiéndose obtener cierto beneficio de su uso en sepsis. Mientras algunos ensayos controlados aleatorizados han encontrado un incremento del riesgo de hasta el 20% de morir o presentar falla orgánica persistente, otros han observado una disminución de la mortalidad de hasta un 40%, además de la estancia hospitalaria y duración de ventilación mecánica. Conclusión: a la fecha, la evidencia es heterogénea respecto al posible beneficio en el uso de vitamina C intravenosa como terapia sola o combinada en el manejo del paciente con sepsis o shock séptico. Mientras los ensayos controlados aleatorizados parecieran demostrar ausencia de beneficio, principalmente respecto a mortalidad o persistencia de falla orgánica a los 28 días, algunos meta-análisis tienden a mostrar una reducción del riesgo de muerte. Por lo tanto, sigue faltando evidencia que amplíe este panorama