Major Histocompatibility Complex Class I Chain-Related α (MICA) STR Polymorphisms in COVID-19 Patients.

The SARS-CoV-2 disease presents different phenotypes of severity. Comorbidities, age, and being overweight are well established risk factors for severe disease. However, innate immunity plays a key role in the early control of viral infections and may condition the gravity of COVID-19. Natural Killer (NK) cells are part of innate immunity and are important in the control of virus infection by killing infected cells and participating in the development of adaptive immunity. Therefore, we studied the short tandem repeat (STR) transmembrane polymorphisms of the major histocompatibility complex class I chain-related A (MICA), an NKG2D ligand that induces activation of NK cells, among other cells. We compared the alleles and genotypes of MICA in COVID-19 patients versus healthy controls and analyzed their relation to disease severity. Our results indicate that the MICA*A9 allele is related to infection as well as to symptomatic disease but not to severe disease. The MICA*A9 allele may be a risk factor for SARS-CoV-2 infection and symptomatic disease.

A propos of a new case of shigellosis by a non-imported multiresistant strain.

We present the case corresponding to a shigellosis produced by multiresistant S. flexneri in a patient with no recent history of tourism or travel to exotic countries. This case exposes the need to know the distribution of resistant strains, and their emergence not imported in our environment, in the face of choosing the most appropriate type of antibiotic, when appropriate.

Cardiorespiratory fitness and age-related arterial stiffness in women with systemic lupus erythematosus.

BACKGROUND: The aim of this study was twofold: (i) to examine the association of cardiorespiratory fitness with arterial stiffness in women with systemic lupus erythematosus; (ii) to assess the potential interaction of cardiorespiratory fitness with age on arterial stiffness in this population. MATERIALS AND METHODS: A total of 49 women with systemic lupus erythematosus (mean age 41.3 [standard deviation 13.8] years) and clinical stability during the previous 6 months were included in the study. Arterial stiffness was assessed through pulse wave velocity (Mobil-O-Graph® 24 hours pulse wave velocity monitor). Cardiorespiratory fitness was estimated with the Siconolfi step test and the 6-minute walk test. RESULTS: Cardiorespiratory fitness was inversely associated with pulse wave velocity in crude analyses (P < .05), although this relationship was attenuated when age and other cardiovascular risk factors were controlled. There was a cardiorespiratory fitness × age interaction effect on pulse wave velocity, regardless of the test used to estimate cardiorespiratory fitness (P < .001 for the Siconolfi step test; P = .005 for the 6-minute walk test), indicating that higher cardiorespiratory fitness was associated with a lower increase in pulse wave velocity per each year increase in age. CONCLUSIONS: The results of this study suggest that cardiorespiratory fitness might attenuate the age-related arterial stiffening in women with systemic lupus erythematosus and might thus contribute to the primary prevention of cardiovascular disease in this population. As the cross-sectional design precludes establishing causal relationships, future clinical trials should confirm or contrast these findings.

Clinical significance of isolation of Haemophilus no ducreyi in genital samples. Systematic review.

INTRODUCTION AND OBJECTIVES: Currently, the microbiological diagnosis of genital infections is carried out with molecular methods, which allow the detection of less frequent etiological agents but with potential pathogenic importance, such as Haemophilus spp. The objective of this review is to analyse and highlight the clinical importance of the isolation of Haemophilus spp. in genital and rectal infections, excluding Haemophilus ducreyi. MATERIAL AND METHODS: A systematic review was carried out based on an exhaustive search of the publications included in the MEDLINE database up to August 5, 2021, on the presence of Haemophilus spp. in genital and rectal infections, excluding H. ducreyi. RESULTS: After reviewing what was described in the literature, Haemophilus spp. (excluding H. ducreyi: HSNOD) was detected in 2397 episodes of genital infection, the most frequently isolated species being H. influenzae and H. parainfluenzae. Most of the episodes (87,6%) are constituted by single isolation. There is a slight predominance in women (48,3%) where it can cause vaginitis, salpingitis, endometritis or complications during pregnancy. In men, the clinical picture usually corresponds to urethritis. Most of the samples correspond to vaginal and urethral exudates, with a minority representation at the rectal level (2.3%). CONCLUSION: HSNOD plays a relevant pathogenic role in episodes of genital infection, so microbiological diagnostic protocols must include methods that allow their detection, as well as include them in the etiological spectrum of this type of clinical picture.

Presence and Relevance of Emerging Microorganisms in Clinical Genitourinary Samples.

Microorganisms responsible for genitourinary infections increasingly include species other than conventional etiological agents that are of clinical and pathogenic relevance and therapeutic interest. This cross-sectional descriptive study selected samples from clinical genitourinary episodes between January 2016 and December 2019 in which emerging microbiological agents were detected. The patients' epidemiological characteristics, clinical presentation, antibiotic treatment, and outcome were studied to identify their pathogenic role. The emerging microorganisms most frequently detected in urinary tract infections were Streptococcus bovis (58.5%) and Gardnerella spp. (23.6%) in females and S. bovis (32.3%), Aerococcus urinae (18.6%), and Corynebacterium spp. (16.9%) in males, while the most frequently detected in genital infections were S. viridans (36.4%) in females and C. glucuronolyticum (32.2%) and Gardnerella spp. (35.6%) in males. All cases in female children were produced by S. bovis. Symptomatic episodes were more frequent with Aerococcus spp. and S. bovis and the presence of leukocytosis more frequent with Aerococcus spp. Quinolones and doxycycline were most often prescribed antibiotics for genital infections and quinolones and amoxicillin-clavulanic acid for urinary infections. Urinary infection by Aerococcus spp. was more frequent in males of advanced age, Corynebacterium spp. was more frequent in permanent vesical catheter carriers, and episodes of asymptomatic bacteriuria by Gardnerella spp. were more frequent in patients with kidney transplant and chronic consumers of corticosteroid therapy. Lactobacillus spp. should be considered in urinary infections of patients of advanced age and with a previous antibiotic load. Genital infection by Gardnerella spp. was significantly associated with a history of risky sexual relations.

Antibiotic Resistance Changes in Gram-Positive Bacteria from Urine Cultures: Development Analysis in a Health Area of South-East Spain.

This study analyzed the epidemiology and antibiotic susceptibility profile of significant bacteriuria and assessed the impact of adopting EUCAST criteria on antibiotic resistances. A systematic review was performed on publications in English or Spanish between 1 January 2010 and 30 June 2021 on the susceptibility of Gram-positive bacteria isolated in urinary samples in Europe. A retrospective descriptive study was also conducted on the results of 21,838 urine cultures with presumptive urinary tract infection (UTI) obtained during the past five years by the Department of Microbiology of the Virgen de las Nieves University Hospital (Granada, Spain). The activity of various antibiotics was determined, differentiated among various populations, and interpretations compared according to the application of EUCAST or CLSI criteria. Among 21,838 cases of significant bacteriuria, 27.69% were by Gram-positive bacteria, which were Enterococcus faecalis in 19.04% and Enterococcus faecium in 3.92%. The susceptibility profile remained stable for most antibiotics except for levofloxacin for E. faecalis and Staphylococcus aureus and nitrofurantoin for E. faecium. The resistance of Enterococcus spp. and Staphylococcus spp. to glycopeptides was exceptionally low in our setting. No significant difference in the prevalence of methicillin-resistant Staphylococcus aureus was observed between hospital (26.67%) and community (28.85%) samples. Resistances in our local setting remain stable and appear to be lower than reported in other studies. The adoption of EUCAST vs. CLSI criteria did not produce a general change in resistance rates. Findings suggest the need to revise certain empirical criteria, such as aminoglycoside synergy for Enterococcus and for community-origin S. aureus.

[Isolation of Haemophilus no ducreyi in samples from the genital tract of men: Its clinical relationship]. / Aislamiento de Haemophilus no ducreyi en muestras del aparato genital de varones: relación con la clínica.

INTRODUCTION: With the advancement of microbiological methods, the isolation of less typical pathogens in cases of urethral and rectal infection is more frequent, apart from the classic etiological agents. One of them is formed by species of Haemophilus no ducreyi (HND). The objective of this work is to describe frequency, susceptibility to antibiotics, and clinical features of HDN urethritis and proctitis in adult males. PATIENTS AND METHODS: This is an observational retrospective descriptive study of the results obtained by the Microbiology laboratory of the Virgen de las Nieves University Hospital on the isolates of HND in genital and rectal samples from males between 2016 and 2019. RESULTS: HND was isolated in 135 (7%) of the genital infection episodes diagnosed in men. H. parainfluenzae was the most commonly isolated (34/45; 75.6%). The most frequent symptoms in men with proctitis were rectal tenesmus (31.6%) and lymphadenopathy (10.5%); in those with urethritis, dysuria (71.6%), urethral suppuration (46.7%) and gland lesions (27%), so differentiating it from infections caused by other genitopathogens is difficult. 43% of patients were HIV positive. Antibiotic resistance rates for H. parainfluenzae were high to quinolons, ampicillin, tetracycline and macrolides. CONCLUSION: HND species should be considered as possible etiologic agents in episodes of urethral and rectal infection in men, especially in cases with negative screening tests for agents that cause sexually transmitted infections (STIs). Its microbiological identification is essential for the establishment of an effective targeted treatment.

Blood Culture-Negative Infective Endocarditis by Mycoplasma hominis: Case Report and Literature Review.

Mycoplasma hominis is a habitual colonizing microorganism of the lower genital tract but can exceptionally be the causal agent of blood culture-negative infective endocarditis (IE). Only 11 cases of this entity have been published to date. The study objectives were to describe the first case diagnosed in our center of IE by M. hominis on pacemaker lead and to carry out a narrative review. Among published cases of IE by this microorganism, 72.7% were male, with a mean age of 45 years and a history of valve surgery; the diagnosis was by culture (54.5%) or molecular technique (45.5%), and the prognosis was favorable in 72.7% of cases. The most frequently prescribed antibiotics were doxycycline, quinolones, and clindamycin.

Emerging Presence of Culturable Microorganisms in Clinical Samples of the Genitourinary System: Systematic Review and Experience in Specialized Care of a Regional Hospital.

The detection of emerging pathogens responsible for genitourinary infections has increased with technological advances. We conducted a systematic review of publications on the involvement of these microorganisms in genitourinary samples, and we also investigated their presence and antibiotic susceptibility in samples from patients at our regional hospital (Granada, Spain). The MEDLINE database was searched up to 31 December 2020, and a cross-sectional descriptive study was performed of results obtained in urine samples and genital exudates from January 2016 through December 2019. The review highlighted the frequent involvement of Neisseria meningitidis in genital infections, while the data on other microorganisms were consistent with findings in our patient series. The emerging microorganisms most often responsible for urinary tract infections were Streptococcus bovis (58.5%) and Gardnerella vaginalis (23.6%) in females, and S. bovis (32.3%), Aerococcus urinae (18.6%), and Corynebacterium spp. (16.9%) in males; those most frequently reported in genital infections were S. viridans (36.4%) in females and C. glucuronolyticum (32.2%) and G. vaginalis (35.6%) in males. In general, emerging pathogens are resistant to conventional antibiotics such as penicillin. However, there has also been an increase in beta-lactam resistance by the S. bovis group and Corynebacterium spp. The systematic review showed that emerging microorganisms are responsible for only a small percentage of genitourinary infections but are of major clinical interest, with a predominance of the S. bovis group, G. vaginalis, Lactobacillus spp., Aerococcus spp., and Corynebacterium spp. in urine samples and of G. vaginalis and C. glucuronolyticum in genital samples. Given the increasing resistance to antibiotics empirically prescribed in patients with genitourinary infections, it is recommended to create an antibiogram in all cases.

Effects of 12-week aerobic exercise on patient-reported outcomes in women with systemic lupus erythematosus.

PURPOSE: To evaluate the effects of aerobic exercise on patient-reported outcomes (PROs) in women with systemic lupus erythematosus (SLE), and whether changes in cardiorespiratory fitness (CRF) mediate the changes in PROs. METHODS: A total of 58 women with SLE were assigned to either an exercise group (EG; n = 26) or a control group (CG; n = 32) in this non-randomized clinical trial. The EG comprised 12 weeks of aerobic exercise (2 sessions/week) between 40%-75% of the individual's heart rate reserve. At baseline, and at week 12, CRF (Bruce test) and PROs were assessed including psychological stress (Perceived Stress Scale), sleep quality (Pittsburg Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory), and quality of life (36-item Short-Form Health Survey). RESULTS: In comparison to the CG, the EG showed a significant reduction in general fatigue (mean difference (MD) -2.86 units; 95%CI -5.70 to -0.01; p = 0.049), physical fatigue (MD -4.33 units; 95%CI -7.02 to -1.65; p = 0.002) and a non-significant reduction of reduced motivation (MD - 1.29 units; 95%CI -2.60 to 0.03; p = 0.055). There were no significant between-group differences in the changes in psychological stress, sleep quality, depressive symptoms, quality of life, or other fatigue dimensions (all p > 0.05). Changes in CRF mediated the effects of the exercise intervention on general fatigue by 53.8%. CONCLUSION: The results suggest that 12 weeks of progressive aerobic exercise might improve relevant dimensions of fatigue in women with SLE, despite the absence of effects on other PROs. Improvements in CRF seem to mediate the effect of exercise on general fatigue.Implications for rehabilitationAerobic exercise could be safely introduced in rehabilitation programs for inactive patients with SLE with mild disease activity.Including physical activity recommendations as part of rehabilitation could improve relevant aspects of fatigue in women with SLE.When rehabilitation aims at reducing fatigue, cardiorespiratory fitness improvements derived from physical activity might enhance benefits.

Study of HLA-A, -B, -C, -DRB1 and -DQB1 polymorphisms in COVID-19 patients.

BACKGROUND: Human leukocyte antigen (HLA) plays an important role in immune responses to infections, especially in the development of acquired immunity. Given the high degree of polymorphisms that HLA molecules present, some will be more or less effective in controlling SARS-CoV-2 infection. We wanted to analyze whether certain polymorphisms may be involved in the protection or susceptibility to COVID-19. METHODS: We studied the polymorphisms in HLA class I (HLA-A, -B and -C) and II (HLA-DRB1 and HLA-DQB1) molecules in 450 patients who required hospitalization for COVID-19, creating one of the largest HLA-typed patient cohort to date. RESULTS: Our results show that there is no relationship between HLA polymorphisms or haplotypes and susceptibility or protection to COVID-19. CONCLUSION: Our results may contribute to resolve the contradictory data on the role of HLA polymorphisms in COVID-19 infection.

Emerging presence of urethritis and balanitis by Pasteurella bettyae.

BACKGROUND: Humans can also be infrequent infected by Pasteurella bettyae. We report the first association of P. bettyae with urethritis and balanitis in men who have sex with men practicing unprotected intercourse. PATIENTS AND METHODS: The standard culture for bacteria and fungi in genital samples, and a PCR study for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma spp. and Ureaplasma spp, were performed. Cultured microorganisms were identified by Maldi-Tof mass spectrometry and the susceptibility of the isolates were evaluated with the gradient test. RESULTS: P. bettyae were isolated and were found to be susceptible to penicillin, amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, ciprofloxacin, and doxycycline. CONCLUSION: This novel finding highlights the need for complete microbiological screening in adequate samples to detect possible infectious agents in these cases, not limited to conventional agents. These rare microorganisms can be detected by the application of Maldi-Tof in colonies grown in culture media.

Physical Fitness Attenuates the Impact of Higher Body Mass and Adiposity on Inflammation in Women With Systemic Lupus Erythematosus.

Aims: Higher body mass and adiposity represent independent contributors to the systemic low-grade inflammatory state often observed in patients with systemic lupus erythematosus (SLE). This study assessed the role of physical fitness in the association of body mass and adiposity with inflammation in women with SLE. Methods: A total of 77 women with SLE were included in this cross-sectional study. We obtained body mass index, waist-to-height ratio, and body fat percentage as indicators of body mass and adiposity. Inflammation was assessed through Serum levels of C-reactive protein, interleukin 6, and leptin. Cardiorespiratory fitness was assessed with the 6-minute walk test, range of motion with the back-scratch test, and muscular strength with handgrip dynamometry. Results: Cardiorespiratory fitness attenuated the association of both body mass index and body fat percentage with interleukin 6 (all, P<0.05). Range of motion attenuated the association of body mass index with interleukin 6 (P<0.05) and the association of body fat percentage with C-reactive protein (P<0.05). These interactions indicated that higher fitness was associated with a lower increase in inflammation per unit increase of body mass or adiposity. Muscular strength showed a non-significant trend to attenuate the association of body fat percentage with interleukin 6 (P=0.057) but potentiated the association of body fat percentage with leptin (P<0.05). Conclusion: These findings suggest that higher levels of cardiorespiratory fitness and range of motion might attenuate the impact of higher body mass and adiposity on inflammation in women with SLE. The role of muscular strength requires further investigation.

Relative Handgrip Strength as Marker of Cardiometabolic Risk in Women with Systemic Lupus Erythematosus.

This study aimed to examine the association of relative handgrip strength (rHGS) with cardiometabolic disease risk factors in women with systemic lupus erythematosus (SLE). METHODS: Seventy-seven women with SLE (mean age 43.2, SD 13.8) and clinical stability during the previous six months were included. Handgrip strength was assessed with a digital dynamometer and rHGS was defined as absolute handgrip strength (aHGS) divided by body mass index (BMI). We measured blood pressure, markers of lipid and glucose metabolism, inflammation (high sensitivity C-reactive protein [hs-CRP]), arterial stiffness (pulse wave velocity [PWV]), and renal function. A clustered cardiometabolic risk index (z-score) was computed. RESULTS: Pearson's bivariate correlations revealed that higher rHGS was associated with lower systolic blood pressure (SBP), triglycerides, hs-CRP, PWV, and lower clustered cardiometabolic risk (rrange = from -0.43 to -0.23; all p < 0.05). Multivariable linear regression analyses adjusted for age, disease activity (SLEDAI), and accrual damage (SDI) confirmed these results (all p < 0.05) except for triglycerides. CONCLUSIONS: The findings suggest that higher rHGS is significantly associated with lower cardiometabolic risk in women with SLE.

Ideal cardiovascular health in women with systemic lupus erythematosus: Association with arterial stiffness, inflammation, and fitness.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is closely related to cardiovascular morbidity and mortality. We aimed to examine the association of ideal cardiovascular health (ICH) with arterial stiffness, inflammation, and physical fitness in women with SLE. METHODS: This cross-sectional study included 76 women with SLE (age 43.4±13.8 years old). Ideal levels of 7 health metrics (smoking, body mass index, physical activity, healthy diet, blood pressure, cholesterol, and glucose) were used to define the ICH score (ranging from 0 to 7 ideal metrics) and the ICH status ( defined as presenting ≥4 ideal metrics). Arterial stiffness was measured through pulse wave velocity (PWV) and inflammation through serum high sensitivity C-reactive protein (hs-CRP). Cardiorespiratory fitness (CRF) was measured by 6-min walk test (6MWT), and Siconolfi step test and muscular strength by handgrip strength and 30-s chair stand, and range of motion (ROM) by the back-scratch test. RESULTS: Higher ICH score was associated with lower PWV (ß = -0.122, p = 0.002), lower hs-CRP (ß = -0.234, p = 0.056), higher CRF [6MWT (ß = 0.263, p = 0.041); Siconolfi step test (ß = 0.330, p < 0.001)], higher ROM (ß = 0.278, p = 0.013) and higher relative handgrip strength (ß = 0.248, p = 0.024). Women with ICH status presented lower PWV (mean difference 0.40 m/s, 95% CI 0.17 to 0.63, p = 0.001), and higher CRF [assessed by 6MWT (mean difference 43.9 m, 95% CI 5.0 to 82.7, p = 0.028)], than women with non-ICH status. Sensitivity analyses using ICH score ranging 0-14 and considering ICH status with ≥5 metrics revealed consistent results. CONCLUSION: ICH is associated with lower arterial stiffness, lower inflammation, and higher fitness in women with SLE. Although these results extend current knowledge about the potential role of ICH for primordial prevention of CVD in SLE, they are yet to be confirmed in future prospective research .

Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset.

The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.

Heart Rate Variability in Women with Systemic Lupus Erythematosus: Association with Health-Related Parameters and Effects of Aerobic Exercise.

Abnormal heart rate variability (HRV) has been observed in patients with systemic lupus erythematosus (SLE). In a combined cross-sectional and interventional study approach, we investigated the association of HRV with inflammation and oxidative stress markers, patient-reported outcomes, and the effect of 12 weeks of aerobic exercise in HRV. Fifty-five women with SLE (mean age 43.5 ± 14.0 years) were assigned to either aerobic exercise (n = 26) or usual care (n = 29) in a non-randomized trial. HRV was assessed using a heart rate monitor during 10 min, inflammatory and oxidative stress markers were obtained, psychological stress (Perceived Stress Scale), sleep quality (Pittsburg Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory), and quality of life (36-item Short-Form Health Survey) were also assessed. Low frequency to high frequency power (LFHF) ratio was associated with physical fatigue (p = 0.019). Sample entropy was inversely associated with high-sensitivity C-reactive protein (p = 0.014) and myeloperoxidase (p = 0.007). There were no significant between-group differences in the changes in HRV derived parameters after the exercise intervention. High-sensitivity C-reactive protein and myeloperoxidase were negatively related to sample entropy and physical fatigue was positively related to LFHF ratio. However, an exercise intervention of 12 weeks of aerobic training did not produce any changes in HRV derived parameters in women with SLE in comparison to a control group.