A Low Number of Baselines γδ T Cells Increases the Risk of SARS-CoV-2 Post-Vaccination Infection.

Background: The COVID-19 pandemic is the biggest global health problem in the last hundred years. The efficacy of the vaccine to protect against severe disease is estimated to be 70-95% according to the studies carried out, although there are aspects of the immune response to the vaccine that remain unclear. Methods: Humoral and cellular immunity after the administration of three doses of the Pfizer-BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 were studied. SARS-CoV-2 IgG and IgA antibodies, αß and γδ T-cell subsets, and their differentiation stages and apoptosis were analyzed. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the duration of the study. This increase was the greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αß, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+ CD8+ and CD56+ αß and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to a γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: The results unveil the important role of γδ T cells in SARS-CoV-2-vaccine-mediated protection from the disease.

Latent Microsporidia Infection Prevalence as a Risk Factor in Colon Cancer Patients.

Microsporidia are opportunistic intracellular parasites, generating serious pathology in individuals with a compromised immune system. Infection by microsporidia inhibits p53 and Caspase 3, proteins involved in apoptosis and the cell cycle, which are vital in the malignant process of epithelial cells. The presence of microsporidia in the intestinal tissues of 87 colon cancer (CC) patients and 25 healthy controls was analyzed by real-time PCR and an immunofluorescence antibody test. Anti-Encephalitozoon antibodies were analyzed in serum samples by ELISA (enzyme linked immunosorbent assay). In 36 (41.3%) CC cases, microsporidia infections were identified in their tissues vs. no cases among control subjects (p < 0.0001). An increase in IgG and IgE anti-Encephalitozoon antibodies was found in patients with CC, which would demonstrate continuous and previous contact with the parasite. The high prevalence of microsporidia in tissues and the seroprevalence in patients with CC suggest a relationship between microsporidia and the etiopathogenesis of CC.

Lymphopenia in hospitalized patients and its relationship with severity of illness and mortality.

BACKGROUND: Lymphopenia is associated with various pathologies such as sepsis, burns, trauma, general anesthesia and major surgeries. All these pathologies are clinically expressed by the so-called Systemic Inflammatory Response Syndrome which does not include lymphopenia into defining criteria. The main objective of this work was to analyze the diagnosis of patients admitted to a hospital related to lymphopenia during hospital stay. In addition, we investigated the relationship of lymphopenia with the four levels of the Severity of Illness (SOI) and the Risk of Mortality (ROM). METHOD AND FINDINGS: Lymphopenia was defined as Absolute Lymphocyte Count (ALC) <1.0 x109/L. ALC were analyzed every day since admission. The four levels (minor, moderate, major and extreme risk) of both SOI and ROM were assessed. A total of 58,260 hospital admissions were analyzed. More than 41% of the patients had lymphopenia during hospital stay. The mean time to death was shorter among patients with lymphopenia on admission 65.6 days (CI95%, 57.3-73.8) vs 89.9 (CI95%, 82.4-97.4), P<0.001. Also, patients with lymphopenia during hospital stay had a shorter time to the mortality, 67.5 (CI95%, 61.1-73.9) vs 96.9 (CI95%, 92.6-101.2), P<0.001. CONCLUSIONS: Lymphopenia had a high prevalence in hospitalized patients with greater relevance in infectious pathologies. Lymphopenia was related and clearly predicts SOI and ROM at the time of admission, and should be considered as clinical diagnostic criteria to define SIRS.

Laparoscopic Versus Open Incisional Hernia Repair: Long-Term Follow-up Results of a Randomized Clinical Trial.

PURPOSE: Long-term extension of a previous randomized controlled clinical trial comparing open (OVHR) vs. laparoscopic (LVHR) ventral hernia repair, assessing recurrence, reoperation, mesh-related complications and self-reported quality of life with 10 years of follow-up. METHODS: Eighty-five patients were followed up to assess recurrence (main endpoint), reoperation, mesh complications and death, from the date of index until recurrence, death or study completion, whichever was first. Recurrence, reoperation rates and death were estimated by intention to treat. Mesh-related complications were only assessed in the LVHR group, excluding conversions (intraperitoneal onlay; n = 40). Quality of life, using the European Hernia Society Quality of Life score, was assessed in surviving non-reoperated patients (n = 47). RESULTS: The incidence rates with 10 person-years of follow-up were 21.01% (CI 13.24-33.36) for recurrence, 11.92% (CI: 6.60-21.53) for reoperation and 24.88% (CI 16.81-36.82) for death. Sixty-two percent of recurrences occurred within the first 2 years of follow-up. No significant differences between arms were found in any of the outcomes analyzed. Incidence rate of intraperitoneal mesh complications with 10 person-years of follow-up was 6.15% (CI 1.99-19.09). The mean EuraHS-QoL score with 13.8 years of mean follow-up for living non-reoperated patients was 6.63 (CI 4.50-8.78) over 90 possible points with no significant differences between arms. CONCLUSION: In incisional ventral hernias with wall defects up to 15 cm wide, laparoscopic repair seems to be as safe and effective as open techniques, with no long-term differences in recurrence and reoperation rates or global quality of life, although lack of statistical power does not allow definitive conclusions on equivalence between alternatives. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov (NCT04192838).

Differences in circulating γδ T cells in patients with primary colon cancer and relation with prognostic factors.

Downregulation of the T cell system has been proposed as a mechanism to block immunity in colonic cancer (CC). However, little has been studied about circulating αß and γδ T cells and their immunological status in newly diagnosed patients. The aim of this study was to characterize the αß and γδ T cell subsets in peripheral blood of patients with CC matched with healthy volunteers. In this prospective case-control study, blood samples were obtained from 96 patients with newly diagnosed treatment-naïve infiltrating colonic adenocarcinoma and 48 healthy volunteers. Pathological report at surgery was obtained from all CC patients. A significant decrease in CD3+ γδ T cells and CD3+CD8+ γδ T cells (p<0.001) were observed in CC patients. Apoptosis was significantly increased in all conventional and both αß and γδ T cell subsets in patients with CC vs healthy subjects. γδ T cells were decreased in peripheral blood of patients with microscopic infiltration in tissues, history of cancer and synchronous colon cancer (p < 0.05). IFN-γ was significantly reduced in CC patients compared to controls. Cytotoxic effector γδ T cells TEMRA (CD8 and CD56) are the proportionally most abundant T cells in peripheral blood of CC patients. Patients with CC present a deep downregulation in the systemic T-cell immunity. These variations are evident through all tumor stages and suggest that a deficiency in γδ T cell populations could be preventing control of tumor progression. This fact prove the role of immunomodulation on CC carcinogenesis.

Induction of tolerogenic properties by Anisakis larval antigens on murine dendritic cells.

AIMS: The objective of this work is to investigate whether Anisakis simplex larval antigens present immunomodulatory properties by the induction of tolerogenic dendritic cells (DCs) from two strains of mice (BALB/c and C57BL/6J). METHODS AND RESULTS: We used mouse bone marrow-derived DCs. We determined their antigen-presenting ability by expression of membrane markers (MHC I and MHC II, CD80, CD86) and intracellular expression levels of IL-10 and IL-12 cytokines. We also analysed whether stimulation with A simplex larval antigens is enhanced by the co-administration of the TLR4 and TLR9 agonists [LPS E coli 026B6 and CpG (ODN1826), respectively]. Two differential types of responses were found in the two mouse strains studied: the BALB/c strain showed an acute and inflammatory response, whereas the C57BL/6J mice developed a more discrete and resistant response. This suggests the coexistence of two opposing responses generated by A simplex larval antigens and confirms that the host genetic basis plays a role in the development of a Th2 or Treg response. CONCLUSION: The study of the mechanisms by which Anisakis manipulates the immune response through anti-inflammatory molecules is of interest not only for the direct application on the development of anthelmintic strategies, but also for the development of new anti-inflammatory products.

B1a Lymphocytes (CD19+CD5+) Deficiency in Patients with Crohn's Disease and Its Relation with Disease Severity.

BACKGROUND/AIMS: B1a cells (CD19+CD5+) are considered elements of the innate immune system. The aim of this study was to evaluate the frequency of B1a cells in the peripheral blood of patients with Crohn's disease (CD) and its relation with disease severity. METHODS: In this prospective study, a total of 128 subjects (64 CD patients and 64 healthy controls) were studied. B1a cells in peripheral blood, CD Activity Index, and Simple Endoscopic Score of B1a cells were studied. RESULTS: A significant decrease of B1a cells in peripheral blood was observed in patients with CD versus controls (p = 0.002), especially in perforating or penetrating patterns (p = 0.017). A lower frequency of B1a cells is related to increased endoscopic severity (Spearman's Rho: -0.559, p = 0.004). The mean frequency of B1a cells in patients with pre- and post-study surgery was significantly lower than that in patients who did not undergo surgery (p = 0.050 and p = 0.026, respectively). CONCLUSIONS: The B1a cell count in peripheral blood is lower in CD patients. This decrease is directly related to the severity of the disease (penetrating or perforating, Simple Endoscopy Score and surgery complication). These results pointed to the fact that B1a cells play an important role in immune protection in CD.

Rectal advancement flap for the treatment of complex cryptoglandular anal fistulas: a systematic review and meta-analysis.

PURPOSE: Rectal advancement flap is an accepted approach for treating complex fistula-in-ano. However, a diversity of technical modifications have been described. The aim of this study was to evaluate recurrence and fecal continence rates after performing rectal advancement flaps depending upon flap thickness (full-thickness, partial-thickness, or mucosal flaps) and treatment of the fistulous tract (core-out or curettage). METHODS: Medline (PubMed, Ovid), the Cochrane Library database, and ClinicalTrials.gov were searched. Studies that involved patients with complex cryptoglandular fistulas who had been treated with rectal advancement flaps were included. The outcomes measured were recurrence and fecal continence. All of the statistical analyses were performed using Comprehensive Meta-Analysis software. A fixed model was used if there was no evidence of heterogeneity; otherwise, a random effects model was used. RESULTS: Twenty-six studies were included (1655 patients). The pooled rate of recurrence was 21%. Full-thickness flaps showed the best results concerning recurrence (7.4%), partial flaps revealed 19% and mucosal flaps 30.1%. Core-out and curettage had a similar recurrence (19 vs 21%). Regarding anal incontinence, the pooled rate was 13.3%. Mucosal- and partial-thickness flaps showed similar rates (9.3 vs 10.2%), while full-thickness flaps disturbed it in 20.4%. Most of these alterations were minor symptoms. Otherwise, core-out and curettage showed similar rates (14.3 vs 12%). CONCLUSIONS: 1. Full-thickness rectal advancement flaps offer better results regarding the recurrence than mucosal or partial flaps. 2. All flaps cause some incontinence, which increases with the thickness of the flap. 3. The results did not suggest differences in recurrence and incontinence between core-out and curettage.

Gammadelta T Cells in Crohn's Disease: A New Player in the Disease Pathogenesis?

Crohn's disease [CD] is a chronic relapsing systemic disease affecting the gastrointestinal tract. An altered immune response to commensal intestinal bacteria takes place in genetically predisposed individuals, resulting in chronic inflammation in the gut. Several alterations in the innate immunity mechanisms have been described in recent years. Thus, the study of the immunological aspects of CD, specifically the role of lymphocytes, is a key element for understanding the pathogenesis of the disease.Gammadelta T cells [γδ T cells] constitute only a small proportion of the lymphocytes that circulate in the blood and peripheral organs and they are present mainly in the epithelia, where they can constitute up to 40% of intraepithelial lymphocytes [IEL] in the intestinal mucosa. Due to their lack of major histocompatibility complex [MHC] restriction and their unique plasticity and immune-regulating properties, they are considered key cells in the first line of defence against infections and in wound healing in the gut. Although there is growing experimental and clinical evidence of their implication in inflammatory bowel disease [IBD], including CD, their clinical relevance is still unclear.In this review, we address the possible involvement of γδ T cells in the pathogenesis of CD, reviewing their role against infections and in inflammation and the current evidence suggesting their implication in CD, offering a novel potential target for immunotherapy in IBD.

A quantitative enzyme-linked immunosorbent assay for quantification of secretory immunoglobulin A in serum.

Secretory immunoglobulin A (SIgA) in serum is possibly the best index of SIgA presence in mucosal secretions in digestive tract and the mirror of its immunologic barrier against many pathogenic aggressions. The measurement of salivary SigA alone may be affected by total salivary secretion and its final concentration in the gland lumen is probably not useful as an appropriate index of mucosal secretions in the digestive tract. The usefulness of the determination of SigA against various epitopes in serum from patients with various autoimmune disease has been demonstrated. The aetiology of many digestive related disorders could be triggered by an alteration of mucose SIgA barrier. The determination of Igs is important for different liver diseases and specifically the SIgA in autoimmune diseases such as rheumatoid arthritis. We developed an easy and efficient immunologic assay to quantify SIgA in serum samples.

Deficit of gammadelta T lymphocytes in the peripheral blood of patients with Crohn's disease.

BACKGROUND: Gammadelta T lymphocytes are an important component of innate immunity. Previous studies have shown their role in the development of Crohn's-like colitis in mice. AIMS: The aim of this study was to measure the γδ T lymphocyte levels in Crohn's disease (CD) patients. METHODS: A prospective study of 40 patients with CD compared with 40 healthy subjects (control group) matched by age and sex was undertaken. Lennard-Jones criteria were used for the diagnosis of CD. Disease activity was measured with the Crohn's disease activity index (CDAI). New patients, patients in remission, and patients with active disease were evaluated. Lymphocytic populations of CD3+, CD4+, CD8+, CD56+, CD19+, and αß and γδ subsets were measured in the peripheral blood of all participants. RESULTS: The levels of CD3+, CD4+, CD8+, and CD19+ lymphocytes were decreased in CD patients compared with the control group (P = 0.002, 0.049, 0.003, and 0.023, respectively). Although both γδ and αß T lymphocytes were lower in patients with CD, γδ T subsets showed the lowest levels in CD patients (mean 0.0259 × 10(9)/l) versus healthy controls (mean 0.0769 × 10(9)/l), P < 0.001. In particular, γδ CD8+ T subsets (mean 0.0068 × 10(9)/l) had the largest difference compared to the control group (mean 0.0199 × 10(9)/l), P = 0.008. CONCLUSIONS: There is a decrease in the global lymphocyte population in the peripheral blood of patients with CD compared to healthy controls. This decrease is more evident in γδ T lymphocytes, especially γδ CD8+ T subsets. Our conclusion is that these results support the theory that a complex alteration of immune responses that affects the total numbers and function of γδ T cells is present in CD.

Mifepristona para tratamiento del fibroma uterino / The use of Mifepristone for treatment of the uterine fibroma

OBJETIVOS: Evaluar la eficacia, seguridad y duración de la mejoría clínica en el tiempo de la administración de 5 vs. 10 mg diarios de mifepristona en el tratamiento del fibroma. MÉTODOS: Fueron aleatorizadas a recibir 5 ó 10 mg diarios de mifepristona oral durante 3 meses y fueron seguidas durante 6 meses después, 100 mujeres con fibromatosis uterina sintomática. Se calcularon los volúmenes del fibroma y del útero por ultrasonografÍa abdominal del útero al inicio, al final del tratamiento, 3 y 6 meses después. RESULTADOS: Al final del tratamiento el fibroma se redujo en 38,3 por ciento, p < 0,001, y 47,5 por ciento, p < 0,001, respecto del valor inicial en los grupos de 5 y 10 mg, respectivamente. El volumen del útero se redujo el 27 por ciento (p = 0,001) y 25,1 por ciento (p = 0,001), con respecto al inicio en los grupos de 5 y 10 mg, respectivamente. La prevalencia de los síntomas fue significativamente menor al final de tratamiento y 6 meses después. Seis meses después del tratamiento el tamaño del fibroma era 21, por ciento y 19, por ciento menor que el valor inicial en los grupos de 5 y 10 mg de mifepristona, respectivamente, y el volumen del útero era 2 por ciento y 0,2, por ciento menor que al inicio en los grupos de 5 y 10 mg, respectivamente. No hubo hiperplasia endometrial en ninguno de los grupos de tratamiento. CONCLUSIONES: La dosis de 5 mg tuvo similar eficacia que la de 10 mg y 6 meses después de concluido el tratamiento los tamaños del fibroma y del útero estaban cercanos a los valores pretratamiento, pero se mantenía una notable mejoría clínica

OBJECTIVES: to evaluate the efficacy, safety and duration improvement obtained over the course of time by administering mifepristone for the treatment of fibroids. METHODS: One hundred women with symptomatic uterine myomas were randomized to receive oral mifepristone 5 or 10 mg daily for 3 months with 6 month post-treatment monitoring. The fibroid and uterus sizes were calculated by means of abdominal ultrasound examination at the beginning and at the end of treatment as well as 3 and 6 months later. RESULTS: At the end of treatment the fibroid decreased in size 38.3 por ciento, p < 0.001, and 47.5 por ciento, p < 0.001, respecting to the initial value in the 5 and 10 mg groups, respectively. The uterine volume decreased 27 por ciento (p = 0.001) and 25.1 por ciento (p = 0.001), regarding to initial values in the 5 and 10 mg groups, respectively. Symptom prevalence was significantly less at the end of treatment and 6 months later. Six months after treatment fibroid size was 21 por ciento and 19 por ciento less than the initial value in the 5 and 10 mg mifepristone groups, respectively, and uterine volume was 2 por ciento and 0.2 por ciento less than initial values in the 5 and 10 mg groups, respectively. There was no endometrial hyperplasia in any of the treatment groups. CONCLUSIONS: The 5 mg dose had an efficacy similar to the 10 mg dosage and 6 months after termination of the treatment fibroid and uterine sizes were close to pre-treatment values but a notable clinical improvement was maintained

Epidemiology of sepsis in the Valencian Community (Spain), 1995-2004.

OBJECTIVE: To study the incidence of sepsis in the Valencian Community (Spain) during a period of 10 years (1995-2004). METHODS: We downloaded data on discharge diagnoses of septicemia in all 26 public hospitals in the Valencian Community during the 10-year study period, as well as the additional discharge diagnoses of each patient. RESULTS: We identified 33,767 cases of sepsis during the study period. The age-standardized incidence rates among men increased from 64.11 (95% confidence interval [CI], 60.37-67.85) cases per 100,000 population in 1995 to 114.02 (95% CI, 109.02-118.50) cases per 100,000 population in 2004 (P < .001), and those among women increased from 45.08 (95% CI, 42.01-48.15) cases per 100,000 population in 1995 to 83.62 (95% CI, 79.85-87.39) cases per 100,000 population in 2004 (P < .001). Gram-negative bacteria were the most frequently involved microorganisms (in 21.4% of cases), and there was a significant increase in the number of sepsis cases caused by these organisms from 1999 onward. The mortality rate was approximately 42.5% among patients hospitalized for sepsis, and mortality was associated with organ failure. In addition, mortality was associated with the microorganism responsible not being known, with infection due to fungi, and with polymicrobial sepsis. CONCLUSIONS: The rates of hospitalization both for sepsis overall and for severe sepsis in the Valencian Community (Spain) are lower than those in other countries but are increasing, by 5% each year. The increase in the number of cases in which gram-negative bacteria are the cause of sepsis is notable.

Secretory immunoglobulin A (sIgA) deficiency in serum of patients with GALTectomy (appendectomy and tonsillectomy).

INTRODUCTION: In adult human beings, 80-85% of the immune cells are located in the digestive tract mucosa; hence the importance of the Gut Associated Lymphoid Tissue (GALT) in host defence. We studied the influence of the surgical removal of two important parts of the gut associated with lymphoid tissue (tonsillectomy and appendectomy) on immune parameters. METHODS: One hundred and sixty patients were enrolled in this study. They were divided into four groups of forty patients each and matched for gender and age: group 1, appendectomized and tonsillectomized; group 2, only appendectomized; group 3, only tonsillectomized; and group 4, control group, neither tonsillectomized nor appendectomized. We analysed in blood: hemogram, protein electrophoresis, lymphocytic populations (T4 cells, T8 cells, NK cells), IgG, IgM, IgA immunoglobulin, and their fractions IgA1, IgA2, and secretory IgA. RESULTS: Levels of secretory IgA in serum of patients in group 1 were significantly lower than in the other three groups (1.89 mg/dl, group 1; 2.32 mg/dl, group 2; 2.19 mg/dl, group 3 and 4.97 mg/dl, group 4; p<0.0001). Also, the values found in the two groups that had undergone only one of the operations were clearly lower than in control patients (p<0.0001). In this study, the reduction was sustained for a period of between 3 months and 3 years in appendectomized patients, and more than 20 years in tonsillectomized patients. IN SUMMARY: GALTectomy (appendectomy and tonsillectomy) significantly decreases secretory IgA levels in serum. The decrease is more intense when both operations have been done.