Morbid obesity is associated with mortality and acute kidney injury in hospitalized patients with COVID-19.

BACKGROUND & AIMS: Mexico has one of the highest mortality rates by COVID-19 worldwide. This may be partially explained by the high prevalence of overweight/obesity found in general population; however, there is limited information in this regard. Furthermore, acute kidney injury (AKI) and need for renal replacement therapy (RRT) associated to obesity in patients with COVID-19 are still topics of discussion. AIM: To explore the association of obesity, particularly morbid obesity, with mortality and kidney outcomes in a Mexican population of hospitalized patients with COVID-19. METHODS: Retrospective cohort study of 773 patients with COVID-19 hospitalized in a tertiary-care teaching hospital in the Mexican state of Jalisco. Baseline body mass index was classified as: normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity (30-39.9 kg/m2), and morbid obesity (≥40 kg/m2). AKI was diagnosed according to KDIGO clinical practice guidelines. RESULTS: At baseline, 35% of patients had overweight, 39% obesity and 8% morbid obesity. Patients with obesity were younger, more frequently women and with hypertension than normal weight and overweight patients. Frequency of complications in the univariate analysis were not significantly associated to obesity, however in the multivariate analysis (after adjusting for baseline clinical and biochemical differences), morbid obesity was significantly associated to an increased risk of AKI [OR = 2.70 (1.01-7.26), p = 0.05], RRT [OR = 14.4 (1.46-42), p = 0.02], and mortality [OR = 3.54 (1.46-8.55), p = 0.005]. CONCLUSIONS: Almost half of the sample had obesity and morbid obesity. Morbid obesity was significantly associated to an increased risk of AKI, RRT and mortality in hospitalized patients with COVID-19.

Risk factors for mortality of adult patients with COVID-19 hospitalised in an emerging country: a cohort study.

OBJECTIVE: To describe mortality of in-hospital patients with COVID-19 and compare risk factors between survivors and non-survivors. DESIGN: Prospective cohort of adult inpatients. SETTING: Tertiary healthcare teaching hospital in Guadalajara, Mexico. PARTICIPANTS: All patients with confirmed COVID-19 hospitalised from 25 March to 7 September 2020 were included. End of study: 7 November 2020. PRIMARY OUTCOME MEASURES: Patient survival analysed by the Kaplan-Meier method and comparison of factors by the log-rank test. Mortality risk factors analysed by multivariate Cox's proportional-hazard model. RESULTS: One thousand ten patients included: 386 (38%) died, 618 (61%) alive at discharge and six (0.6%) remained hospitalised. There was predominance of men (63%) and high frequency of overweight-obesity (71%); hypertension (54%); diabetes (40%); and lung (9%), cardiovascular (8%) and kidney diseases (11%); all of them significantly more frequent in non-survivors. Overweight-obesity was not different between groups, but severity of disease (Manchester Triage System and quick Sequential Organ Failure Assessment) was significantly worse in non-survivors, who were also significantly older (65 vs 45 years, respectively) and had haematological, biochemical, coagulation and inflammatory biomarkers more altered than survivors. Mortality predictors were invasive mechanical ventilation (IMV; OR 3.31, p<0.0001), admission to intensive care unit (ICU; OR 2.18, p<0.0001), age (OR 1.02, p<0.0001), Manchester Triage System (urgent OR 1.44, p=0.02; immediate/very urgent OR 2.02, p=0.004), baseline C reactive protein (CRP; OR 1.002, p=0.009) and antecedent of kidney disease (OR 1.58, p=0.04) CONCLUSIONS: Mortality in hospitalised patients with COVID-19 in this emerging country centre seemed to be higher than in developed countries. Patients displayed a high frequency of risk factors for poor outcome, but the need for IMV, ICU admission, older age, more severe disease at admission, antecedent of kidney disease and higher CRP levels significantly predicted mortality.

Genotypic Analyses of the Sclerostin rs851056 and Dickkopf rs1569198 Polymorphisms in Mexican-Mestizo Postmenopausal Osteoporosis: A Case-Control Study.

Background: The Wnt/ß catenin pathway promotes bone mineralization stimulating proliferation, differentiation, and survival of osteoblasts; it also inhibits osteoclast differentiation and osteocyte activity. Sclerostin (SOST) and Dickkopf 1 (DKK1) are Wnt/ß catenin pathway inhibitors. Genetic variability in the expression of SOST and DKK1 might be involved in the development of postmenopausal osteoporosis (OP). Aim: To determine whether the SOST rs851056 and DKK1 rs1569198 polymorphisms are associated with OP in Mexican-Mestizo postmenopausal women. Materials and Methods: Two hundred and eighty Mexican-Mestizo postmenopausal women were assessed for their bone mineral density by dual-energy X-ray absorptiometry (DXA). Patients were classified as OP or non-OP. Genomic DNA was extracted from peripheral blood leukocytes. Genetic polymorphisms were analyzed by quantitative polymerase chain reaction using TaqMan probes. Results: The frequency of OP was 40% among the study population. Osteoporotic patients were older (p < 0.001), had a higher frequency of smoking (p = 0.01), and lower body mass index (p < 0.001) compared with the non-osteoporotic patients. The genotypic frequencies of the rs851056 locus of the SOST gene were GG 19%, GC 45%, and CC 35%, whereas the genotypic frequencies of the rs1569198 locus of the DKK1 gene were GG 15%, GA 40%, and AA 44%. In relation to rs851056 locus of the SOST gene, no differences were observed between the OP and non-OP cohorts in the frequencies of the GC polymorphism (48.7% vs. 43.1%). Similarly, analyses of the DKK1 rs1569198 does not demonstrate differences in the GA genotypic frequencies between the OP and non-OP cohorts (42.5% vs. 38.9%). Conclusion: Polymorphisms SOST rs851056 and DKK1 rs1569198 polymorphisms are not associated with OP in Mexican-Mestizo postmenopausal women.

Myositis-Specific Antibodies and Myositis-Associated Antibodies in Patients With Idiopathic Inflammatory Myopathies From the PANLAR Myositis Study Group.

BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) are forms of idiopathic inflammatory myopathies (IIMs), which are associated with the production of autoantibodies that are useful in the diagnosis and prognosis of the disease. OBJECTIVE: The aim of this study was to determine the frequency of antinuclear autoantibodies (ANAs), myositis-specific autoantibodies (MSAs), and myositis-associated autoantibodies (MAAs) in 6 Latin American countries. METHODS: Two hundred ten patients with IIM were included in this cross-sectional study from 2014 to 2017: 112 from Mexico, 46 from Colombia, 20 from Peru, 16 from the Dominican Republic, 10 from Argentina, and 6 from Guatemala. Antinuclear autoantibodies were detected by indirect immunofluorescence on HEp-2 cells. MSAs and MAAs were tested by a line immunoassay method. Mann-Whitney U and χ2 tests were used for statistical analysis. RESULTS: Of the 210 IIM patients, 139 (66.2%) had DM, 59 (28%) PM, and 12 (5.7%) juvenile DM. The mean age was 43.5 (6-79 years); 158 (75.2%) were female, and 52 (24.8%) were male. The overall frequency of ANA was 60%. The most frequent patterns were fine speckled (AC-4) (78.3%) and cytoplasmic (AC-19) (6.45%). The most frequent MSA were anti-Mi-2 (38.5%) and anti-Jo-1 (11.9%). Anti-Mi-2 was more frequent in patients from Colombia (40.1%). The MAA more frequent were anti-Ro-52/TRIM21 (17.6%) and anti-PM-Scl75 (7.5%). CONCLUSIONS: This is the first study of ANA, MSA, and MAA in patients from 6 countries from the Panamerican League against Rheumatism myositis study group. We observed a general prevalence of 60% of ANA. In relation to MSA and MAA, anti-Mi-2 was the more frequent (38.5%).

Presence of Acute Chagas Disease Among Febrile Patients in the Western Coast of Mexico.

Chagas disease (ChD) is a parasitosis caused by the protozoan Trypanosoma cruzi (Tc). It is endemic to almost all Latin American countries, including the southern United States. The acute form of ChD and its actual incidence have rarely been described in Mexico, despite the extensive presence of favorable niches for its transmission. The objective of this study was to estimate the frequency of acute ChD in febrile patients at the central Pacific coast of Mexico. For this, we surveyed patients with persistent fever (5 to 10 days) in five hospitals at the Mexican states of Jalisco, Colima, and Nayarit in 2012. Samples were taken from a total of 485 patients to detect Tc in blood using the polymerase chain reaction (PCR) test and direct microscopic examination. Of these subjects, 10 were positive for PCR and none for microscopic examination (2% in 12 months). We adjusted this rate by the total people at risk in the area and obtained an incidence of 7.4/100,000 habs./year. The positive cases showed no association with sex, rural settlement, or pet ownership, only with the contact with Triatominae insects (odds ratio = 9.22 and confidence interval: 1.93-44.06). The clinical picture of positive patients showed an association with the diagnosis of lower respiratory tract infections. Meanwhile, only one fatal case showed the typical picture of acute fatal cardiomyopathy. The pulmonary manifestations of our patients suggest possible lung pathogenicity of Tc, which merits further investigation. Our findings differ markedly from the official reports for ChD. This difference suggests an underestimation of the disease. These findings urge the Mexican health authorities to implement more vigorous actions aimed at improving medical skills in the timely diagnosis of ChD, as well as to apply efficient preventive programs.

Enalapril Influence on Arterial Stiffness in Rheumatoid Arthritis Women: A Randomized Clinical Trial.

Introduction: Cardiovascular parameters disruption can be found in patients at early stages of rheumatoid arthritis (RA). The primary endpoint of this study was the reduction of arterial stiffness in RA patients without traditional cardiovascular risk factors or previous comorbidities, measured by cardio-ankle vascular index (CAVI) through the enalapril intervention. The secondary endpoints were the enalapril influence on carotid femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT), carotid artery distensibility (cDistensibility), Young's incremental elastic modulus (Einc)]. Materials and Methods: Fifty-three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) or placebo (26), both twice a day. The drug was acquired at Victory Enterprises®. The placebo was kindly provided by the Universidad de Guadalajara (UdeG), as well as the blinding into two groups: A and B. Enalapril and placebo were packed into bottles without labeling. Clinical assessment included a structured questionnaire to gather demographic and clinical variables as well as determination of CAVI, cfPWV, cIMT, carotid artery distensibility and Einc. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention. Results: The CAVI measurement at baseline was 7.1 ± 1.4 and increased up to 7.5 ± 1.2 at the end of 12 weeks. Meanwhile, the enalapril group was as follows: 7.4 ± 1.2 and at the of intervention, reduced to 7.1 ± 0.9. A reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP). Discussion: Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context might be interpreted as a reduction of 6.4 years of arterial aging. Trial Registration: The protocol was approved by the Institutional Review Board with the register CI-0117 from UdeG, and 0211/18 from Hospital Civil "Dr. Juan I. Menchaca", Secretaría de Salud Jalisco: DGSP/DDI/D.INV.28/18 and retrospectively registered at ClinicalTrials.gov Protocol Registration and Results System: NCT03667131.

Obesity, Thrombotic Risk, and Inflammation in Cancer.

Neoplasms exhibits a high incidence and mortality rates due to their complex and commonly overlapping clinical, biochemical, and morphologic profiles influenced by acquired or inherited molecular abnormalities, cell of origin, and level of differentiation. Obesity appears related to ~20% of cancers including endometrial, esophageal, colorectal, postmenopausal breast, prostate, and renal. Several factors other than obesity, i.e., insulin, insulin-like growth factor, sexual hormones, and adipokines may play a potential role in neoplasia. Cancer-associated hypercoagulable and thrombotic states are influenced by abnormalities in the vascular wall and susceptibility to invasion, interference in blood flow and increase in circulating tissue factor and thrombin, activation of cell growth factors, the presence of a central catheter, chemotherapies, neoplasm type, and surgery. In cancer, thromboembolic complications are the second most frequent cause of death with pulmonary thromboembolism in ~50% of cases postmortem. Thrombosis worsens prognosis as demonstrated with a survival rate as low as 12% per year vs 36% in nonthrombic patients. Deep vein thrombosis is the most frequent thromboembolic complication in cancer. It is usually detected at diagnosis and within the first 3 months of chemotherapy. The underlining mechanisms of this association should be further studied to identify patients at higher risk and develop adequate prevention, diagnostic, and treatment measures. The D-dimer test can be successfully used to assess the fibrinolytic phase of coagulation and as such is routinely used in suspected cases of deep vein thrombosis and pulmonary thromboembolism. In addition, significant advances have been made in understanding the composition and functional capabilities of the gut microbiota in the inflammatory process, obesity, and its roles in cancer; however, the intricate balance that exists within the microbiota may not only affect the host directly, it can also disrupt the entire microbial community. CONCLUSIONS: Cancer is a prothrombotic and inflammatory state in which the activation of coagulation is related to tumor growth, angiogenesis, and metastasis. It is important to identify the relationship between body mass index with these processes and clarify their importance in cancer prognosis. Future research should answer the question if manipulation of resident microbial communities could potentially improve prognosis and treatment outcome.

Niveles de propéptido aminoterminal de procolágeno tipos I y III y gravedad de la enfermedad pulmonar intersticial en mujeres mexicanas con esclerosis sistémica progresiva / Procollagen Type I and III Aminoterminal Propeptide Levels and Severity of Interstitial Lung Disease in Mexican Women With Progressive Systemic Sclerosis

Antecedentes: La enfermedad pulmonar intersticial (EPI) es una complicación frecuente en la esclerosis sistémica (ES) progresiva, presente en el 25-90% de los pacientes. Objetivo: Evaluar si los niveles séricos de propéptido aminoterminal de procolágeno tipos i y iii (PINP y PIIINP) se correlacionan con la gravedad de la EPI en mujeres mexicanas con ES. Métodos: En 33 pacientes con ES se evaluaron las características de la enfermedad, anticuerpos antitopoisomerasa (topo i), pruebas de función pulmonar y tomografía computarizada de alta resolución (TCAR). Diecinueve pacientes tenían ES + EPI y 14 no presentaban afectación pulmonar (ES sin EPI). Se compararon con 45 controles sanos. Se evaluaron PINP y PIIINP en los 3 grupos. Resultados: El grupo ES tuvo mayores niveles de PINP y PIIINP que el control (p = 0,001 y p < 0,001, respectivamente). Las pacientes ES + EPI habían presentado la enfermedad más años que las ES sin EPI (p = 0,005), tenían mayor puntuación en el índice modificado de Rodnan (p < 0,001), puntuación alta en el índice de evaluación de discapacidad (p < 0,001), mayores niveles de antitopoisomerasa i (p < 0,001), PINP (49,28 ± 28,63 vs. 32,12 ± 18,58 μg/l, p = 0,05), y PIIINP (4,33 ± 1,03 vs. 2,67 ± 1,26 μg/l, p < 0,001). La gravedad de la EPI en TACAR se correlacionó con los niveles de PINP (r = 0,388, p = 0,03) y PIIINP (p = 0,594, p < 0,001). En el análisis ajustado, la gravedad de la EPI se asoció con la duración de la enfermedad (p = 0,037) y con los niveles de PIIINP (p = 0,038) y de antitopoisomerasa i (p = 0,045). Conclusiones: El PINP y el PIIINP son marcadores útiles para la ES + EPI grave. Esto apoya su uso clínico para el seguimiento de esta complicación

Background: Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases. Objectives: To evaluate whether serum levels of procollagen type i and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc. Methods: Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topo i), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD + SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups. Results: Patients with SSc had higher PINP and PIIINP vs controls (P = .001, P < .001, respectively). Compared to no ILD-SSc patients, those with ILD + SSc had longer disease duration in years (P = .005), higher modified Rodnan skin score (P < .001), higher Health Assessment Questionnaire-Disability-Index scores (P < .001), higher topo i U/mL (P < .001), PINP (49.28 ± 28.63 vs. 32.12 ± 18.58 g/L, P = .05), and PIIINP (4.33 ± 1.03 vs. 2.67 ± 1.26 g/L, P < .001) levels. ILD severity based on total HRCT correlated with PINP (r = .388, P = .03) and PIIINP (P = .594, P < .001). On adjusted analysis, ILD severity was associated with disease duration (P = .037), PIIINP (P = .038), and topo i (P = .045). Conclusions: PINP and PIIINP are useful markers for severe ILD + SSc, suggesting they could play a role in the follow-up of this complication in SSc

Procollagen Type I and III Aminoterminal Propeptide Levels and Severity of Interstitial Lung Disease in Mexican Women With Progressive Systemic Sclerosis.

BACKGROUND: Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases. OBJECTIVES: To evaluate whether serum levels of procollagen typei and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc. METHODS: Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topoi), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD+SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups. RESULTS: Patients with SSc had higher PINP and PIIINP vs controls (P=.001, P<.001, respectively). Compared to no ILD-SSc patients, those with ILD+SSc had longer disease duration in years (P=.005), higher modified Rodnan skin score (P<.001), higher Health Assessment Questionnaire-Disability-Index scores (P<.001), higher topoi U/mL (P<.001), PINP (49.28±28.63 vs. 32.12±18.58µg/L, P=.05), and PIIINP (4.33±1.03 vs. 2.67±1.26µg/L, P<.001) levels. ILD severity based on total HRCT correlated with PINP (r=.388, P=.03) and PIIINP (P=.594, P<.001). On adjusted analysis, ILD severity was associated with disease duration (P=.037), PIIINP (P=.038), and topoi (P=.045). CONCLUSIONS: PINP and PIIINP are useful markers for severe ILD+SSc, suggesting they could play a role in the follow-up of this complication in SSc.