Gastrin and the Moderate Hypergastrinemias.

The antral hormone gastrin potently regulates gastric acid secretion and fundic mucosal growth. Consequently, appropriate gastrin secretion and plasma concentrations are important for the early phases of digestion. This review describes as the first premise the normal biogenesis of gastrin in the antral mucosa, but also mentions the extraantral expression. Subsequently, the molecular nature and concentration levels of gastrin in serum or plasma are overviewed. Third, assays for accurate measurements of plasma or serum concentrations are commented. Finally, the problem of moderate hypergastrinemia due to Helicobacter pylori infections and/or treatment with proton-pump inhibitors (PPI) is discussed. The review concludes that accurate measurement of the true concentrations of bioactive gastrins in plasma is important. Moreover, it suggests that moderate hypergastrinemias are also essential health issues that require serious attention.

Alcohol-related Liver Disease and sepsis.

OBJECTIVE: Sepsis is one of the most common complications and causes of death in patients with Alcohol-related Liver Disease. This narrative review will focus on several aspects of sepsis in the context of Alcohol-related Liver Disease. The pathophysiology of the increased susceptibility to infections consists mainly of impaired innate and adaptive immunity, changes in gut microbiota with consequent gut translocation of bacteria due to both alcohol abuse and the underlying liver disease. The diagnosis of sepsis in the context of Alcohol-related Liver Disease is challenging. Moreover, the use of classical acute-phase serum proteins (e.g., C-reactive protein and procalcitonin) has several limitations in this setting. The early administration of an adequate antibiotic treatment is pivotal. Finally, measures of infection control and prevention are needed because the prognosis of sepsis in patients affected by Alcohol-related Liver Disease is poor.

Antígenos del sistema sanguíneo ABO como factor de riesgo para la gravedad de la infección por SARS-CoV-2 / Blood system ABO antigens as risk factor for severity of SARS-CoV-2 infection

Resumen Introducción: Se desconoce si existe una influencia del sistema sanguíneo ABO en susceptibilidad y gravedad de la enfermedad. Objetivo: Analizar si existe una asociación entre los antígenos del sistema ABO y la susceptibilidad y gravedad de la infección por SARS-CoV-2. Material y métodos: Se compararon las frecuencias de los antígenos del sistema ABO en 73 casos confirmados de infección por SARS-CoV-2 y 52 donadores clínicamente sanos. La gravedad de la infección se evaluó comparando la frecuencia de los antígenos por gravedad de la enfermedad y la mortalidad. Resultados: El riesgo de padecer infección por SARS-CoV-2 se incrementa en sujetos con antígeno A vs los no-A (OR=1.45; IC95 %:1.061-1.921). El fenotipo sanguíneo O disminuye el riesgo de padecer infección por SARS-CoV-2 (OR=0.686; IC95 %: 0.522-0.903). No se encontraron diferencias entre la gravedad de la enfermedad. En los pacientes graves, el riesgo de mortalidad se incrementó en sujetos con antígeno A vs los no-A (OR= 3.34; IC95 %: 1.417-8.159). Conclusión: El grupo sanguíneo A es un factor de riesgo para padecer infección por SARS-CoV-2, no así en la gravedad de la enfermedad, pero en los pacientes graves fue un factor de riesgo para la mortalidad.

Abstract Introduction: Whether there is an influence of the ABO blood system on susceptibility to the disease and its severity is unknown. Objective: To analyze if there is an association between the ABO blood system phenotypes and susceptibility to SARS-CoV-2 infection and its severity. Material and methods: The frequency of ABO antigens was compared in 73 confirmed cases of SARS-CoV-2 infection and 52 clinically healthy donors. The severity of the infection was evaluated by comparing the frequency of antigens by severity of the disease and mortality. Results: The risk of SARS-CoV-2 infection is increased in subjects with antigen A vs non-A subjects (OR=1.45; 95 %: 1.061-1.921). Blood phenotype O decreases the risk of SARS-CoV-2 infection (OR= 0.686; 95 % CI: 0.522-0.903). No differences were found regarding disease severity. The mortality risk is increased in subjects antigen A vs non-A (OR= 3.34; 95% IC: 1.417-8.159). Conclusion: Blood group A is a risk factor for SARS-CoV-2 infection, but not for disease severity, although in critically ill patients it is a risk factor for mortality.

Evaluation of patients with primary immunodeficiency associated with Bacille Calmette-Guerin (BCG)-vaccine-derived complications.

BACKGROUND: Bacille Calmette-Guerin (BCG) vaccination has a great impact on the prevention of severe complications of tuberculosis. However, in patients with primary immunodeficiencies (PID), it can lead to severe complications such as severe combined immunodeficiency, chronic granulomatous disease, and Mendelian susceptibility to mycobacterial disease. This study highlights the demographics, clinical complications and laboratory parameters among PID patients associated with BCG vaccination side effects. METHODS: One hundred and thirty-seven PID patients with BCGosis were evaluated in this study, based on the complications following BCG vaccination. RESULTS: The mean age of the patients with BCG complications at the time of the first visit was five years. The within-group comparison of patients showed a highly significant incidence of pneumonia and hepatomegaly in severe combined immunodeficiency patients. Furthermore, the immunologic data showed an increase in the overall rates of lymphocytes such as CD3+, CD4+ and CD8 + T cells in Mendelian susceptibility to mycobacterial disease patients. The level of immunoglobulins has also increased in chronic granulomatous disease patients. CONCLUSION: The high rate of undiagnosed PIDs predisposes individuals to a high risk of severe side effects as a result of BCG vaccination, as well as infants that are less than one month of age. Therefore, there is a need for early screening and diagnosis of PIDs before exposing unknown PID status patients to BCG vaccination. The benefits of screening and early diagnosis of PID cannot be overemphasized, especially in patients with a previous family history of immunodeficiency.

Cardio-metabolic risk factors among young infertile women: a systematic review and meta-analysis.

BACKGROUND: There is currently no concise systematic review or meta-analysis addressing cardio-metabolic risk factors in women experiencing infertility. OBJECTIVES: To determine whether infertile women have higher levels of cardiovascular risk factors compared with fertile women. SEARCH STRATEGY: We performed a systematic literature search using PubMed, Embase and CINAHL, Scopus and additional manual and bibliographic searches for relevant articles (end search date 6 November 2019). SELECTION CRITERIA: We selected studies that compared cardio-metabolic risk factors in fertile and infertile women of reproductive age. DATA COLLECTION AND ANALYSIS: At least two authors independently screened potentially eligible studies. MAIN RESULTS: There was an increased presence of several cardio-metabolic risk factors in infertile women compared with fertile women. Infertile women had statistically significant higher body mass index (BMI), increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) compared with fertile women. Fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and mean arterial pressure were not found to be different between fertile and infertile women. A subgroup analysis revealed that TC, fasting glucose and fasting insulin were increased, and high-density lipoprotein was decreased only in women with polycystic ovarian syndrome compared with fertile women, whereas BMI, TG and LDL-C were statistically significantly increased in women with any indication of infertility compared with fertile women. CONCLUSIONS: Infertile women have a higher level of cardio-metabolic risk factors compared with fertile women. This finding has clinical implications for infertile women in general, and those attempting to conceive through medically assisted reproduction. TWEETABLE ABSTRACT: Infertile women appear to have a higher level of cardio-metabolic risk factors compared with fertile women.

Dehydroepiandrosterone sulfate, free testosterone, and sex hormone-binding globulin on susceptibility to attention-deficit/hyperactivity disorder.

The neuroendocrine system may affect the pathophysiology of gender differences in attention deficit/hyperactivity disorder (ADHD). This study examines whether the relationships among dehydroepiandrosterone sulfate (DHEA-S), free testosterone, or sex hormone-binding globulin (SHBG) and ADHD presentations exhibit gender differences. A total of 113 boys and 35 girls with ADHD (all drug naïve) and 46 and 26 healthy control boys and girls, respectively, were recruited. Blood samples were obtained to measure the serum levels of DHEA-S, free testosterone, and SHBG in each child. The Swanson, Nolan, and Pelham Scale for ADHD Version IV (SNAP-IV) was used to evaluate behavioral symptoms and the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and the Conners' Continuous Performance Test (CPT) were utilized to assess neurocognitive functions. Patients with ADHD had lower DHEA-S levels than male and female healthy control subjects, and no significant differences were observed in free testosterone and SHBG levels between the patients and the controls. DHEA-S levels were negatively correlated with children's impulsivity performance in the CPT. SHBG levels were negatively correlated with ADHD behavior symptoms among boys. Free testosterone levels were not significantly correlated with either ADHD clinical symptoms or neuropsychological functions. We propose that DHEA-S serves as a potential biomarker of ADHD and is consistently involved in the pathogenesis of ADHD in both boys and girls. SHBG may be involved in behaviors associated with ADHD in boys. Additional studies with basic scientific measures are warranted to elucidate the relationship between androgen hormones and clinical presentations of ADHD.

Circulating sCD27 and sCD30 in pre-diagnostic samples collected fifteen years apart and future non-Hodgkin lymphoma risk.

Elevated serum sCD27 and sCD30 from a single banked sample have been associated with future non-Hodgkin lymphoma risk (NHL); however, the etiologic relevance of this finding is unclear. To address this question, we conducted a case-control study (235 cases, 235 controls) nested within the CLUE-I and CLUE-II cohorts, which enrolled participants in 1974 and 1989 respectively in Washington County, Maryland. Our study features a subset of 102 cases and 102 controls with two banked pre-diagnostic samples each, collected 15 years apart. In analyses involving an individual sample per subject, both sCD27 and sCD30 were associated with NHL diagnosed up to 20 years later. In analyses involving repeated samples, cases were significantly more likely than controls to have higher analyte levels in the CLUE-II vs. CLUE-I sample for sCD27 (p = 0.006) but not sCD30 (p = 0.16). In joint analyses of dichotomized analyte levels in both samples, the strongest NHL association observed for sCD27 was for having below-median levels in CLUE-I and above-median levels in CLUE-II [odds ratio (OR) 3.6, 95% confidence interval (CI) 1.4-9.2 vs. below-median levels in both). In joint analyses for sCD30, the strongest NHL association was observed for having above-median levels in both samples (OR 1.7, 95% CI 0.8-3.7), particularly for cases diagnosed >10 years after the CLUE-II sample (OR 2.4, 95% CI 0.9-6.7). Our findings suggest that sCD27 is a disease marker for NHL and add to the weight of evidence that elevated circulating sCD30 is a marker of increased NHL susceptibility.

Sex disparity in viral load, inflammation and liver damage in transgenic mice carrying full hepatitis B virus genome with the W4P mutation in the preS1 region.

AIM: To study sex disparity in susceptibility to hepatocellular carcinoma (HCC), we created a transgenic mouse model that expressed the full hepatitis B virus (HBV) genome with the W4P mutation. METHODS: Transgenic mice were generated by transferring the pHY92-1.1x-HBV-full genome plasmid (genotype A2) into C57Bl/6N mice. We compared serum levels of hepatitis B surface antigen (HBsAg), interleukin (IL)-6, and the liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), as well as liver histopathological features in male and female transgenic (W4P TG) mice and in nontransgenic littermates of 10 mo of age. RESULTS: W4P TG males exhibited more pronounced hepatomegaly, significantly increased granule generation in liver tissue, elevated HBsAg expression in the liver and serum, and higher serum ALT and IL-6 levels compared to W4P TG females or littermate control groups. CONCLUSION: Together, our data indicate that the W4P mutation in preS1 may contribute to sex disparity in susceptibility to HCC by causing increased HBV virion replication and enhanced IL-6-mediated inflammation in male individuals. Additionally, our transgenic mouse model that expresses full HBV genome with the W4P mutation in preS1 could be effectively used for the studies of the progression of liver diseases, including HCC.

Emodiversity and biomarkers of inflammation.

There is growing evidence that inflammatory responses may help to explain how emotions get "under the skin" to influence disease susceptibility. Moving beyond examination of individuals' average level of emotion, this study examined how the breadth and relative abundance of emotions that individuals experience-emodiversity-is related to systemic inflammation. Using diary data from 175 adults aged 40 to 65 who provided end-of-day reports of their positive and negative emotions over 30 days, we found that greater diversity in day-to-day positive emotions was associated with lower circulating levels of inflammation (indicated by IL-6, CRP, fibrinogen), independent of mean levels of positive and negative emotions, body mass index, anti-inflammatory medications, medical conditions, personality, and demographics. No significant associations were observed between global or negative emodiversity and inflammation. These findings highlight the unique role daily positive emotions play in biological health. (PsycINFO Database Record

Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome.

OBJECTIVE: There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. DESIGN: Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. METHODS: In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. RESULTS: All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. CONCLUSION: LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B.

Cytokine mediated changes of pain sensitivity in predisposition to substance dependence.

The purpose of study was evaluation of extra and intracellular cytokine production in blood cultures and cytokine-pain relationship at different stages od addiction. Methods: Classic and multiplex enzyme immunoassay, flow, cytometry, algometry, visual analogue scale were used in 34 abusers, 12 users and 20 control subjects. Results: Cytokine profile correlated with clinical parameters and pain sensitivity in abusers (mostly IL-6 and IL-1ß). IL-10 production is increased in episodic and systematic users. Activation of intracellular IL-6 synthesis was found in users. Both parameters are expected to affect the emotional evaluation of pain. Conclusion: To assess the predisposition to substance dependence most informative are balance of extra and intracellular production of IL-6 and IL-10 and algometry.

Quantitative measurements of brain iron deposition in cirrhotic patients using susceptibility mapping.

BACKGROUND: Susceptibility-weighted imaging (SWI) has been used to detect micro-bleeds and iron deposits in the brain. However, no reports have been published on the application of SWI in studying iron changes in the brain of cirrhotic patients. PURPOSE: To compare the susceptibility of different brain structures in cirrhotic patients with that in healthy controls and to evaluate susceptibility as a potential biomarker and correlate the measured susceptibility and cadaveric brain iron concentration for a variety of brain structures. MATERIAL AND METHODS: Forty-three cirrhotic patients (27 men, 16 women; mean age, 50 ± 9 years) and 34 age- and sex-matched healthy controls (22 men, 12 women; mean age, 47 ± 7 years) were included in this retrospective study. Susceptibility was measured in the frontal white matter, basal ganglia, midbrain, and dentate nucleus and compared with results gathered from two postmortem brain studies. Correlation between susceptibility and clinical biomarkers and neuropsychiatric tests scores was calculated. RESULTS: In cirrhotic patients, the susceptibility of left frontal white matter, bilateral caudate head, and right substantia nigra was higher than that in healthy controls (P < 0.05). There was a positive correlation between susceptibility and iron concentration from one postmortem brain study (r = 0.835, P = 0.01) in eight deep grey matter structures and another in five brain structures (r = 0.900, P = 0.03). The susceptibility of right caudate head (r = 0.402) and left caudate head (r = 0.408) correlated with neuropsychological test scores (both P < 0.05). CONCLUSION: Abnormal iron deposits occur in cirrhotic patients and abnormal susceptibility of some brain regions appears to reflect neurocognitive changes.

Blood Type O is not associated with increased blood loss in extensive spine surgery.

STUDY OBJECTIVE: To investigate whether Type O blood group status is associated with increased intraoperative blood loss and requirement of blood transfusion in extensive spine surgery. DESIGN: Retrospective comparative study. SETTING: University-affiliated, non-profit teaching hospital. MEASUREMENTS: Data from 1,050 ASA physical status 1, 2, 3, 4, and 5 patients who underwent spine surgeries involving 4 or more vertebral levels were analyzed. Patients with Type O blood were matched to similar patients with other blood types using propensity scores, which were estimated via demographic and morphometric data, medical history variables, and extent of surgery. Intraoperative estimated blood loss (EBL) was compared among matched patients using a linear regression model; intraoperative transfusion requirement in volume of red blood cells, fresh frozen plasma, platelet, cryoprecipitate, cell salvaged blood, volume of intraoperative infusion of hetastarch, 5% albumin, crystalloids, and hospital length of hospital (LOS) were compared using Wilcoxon rank-sum tests. MAIN RESULTS: Intraoperative EBL and requirement of blood product transfusion were similar in patients with Type O blood group and those with other blood groups. CONCLUSION: There was no association between Type O blood and increased intraoperative blood loss or blood transfusion requirement during extensive spine surgery, with similar hospital LOS in Type O and non-O patients.

Tobacco smoking associated with the increases of the bronchoalveolar levels of interleukin-5 and interleukin-1 receptor antagonist in acute eosinophilic pneumonia.

BACKGROUND: There is a strong association between tobacco smoking and acute eosinophilic pneumonia (AEP) and tobacco smoking has been related to onset of AEP, but the mechanisms for causing AEP are largely unknown. AEP is characterized by locally high levels of interleukin-5 (IL-5) and interleukin-1 receptor antagonist (IL-1RA). Thus, tobacco smoking may relate to the high levels of IL-5 and IL-1RA in AEP. AIM: We aimed to determine whether the rate of tobacco smoking positively related to the high levels of IL-5 and IL-1RA. PATIENTS AND METHODS: In the study, 155 AEP patients and 135 control healthy subjects were recruited by the Clinical Research Center at General Hospital of Shenyang Military Area Command (Shenyang, China). All the subjects were interviewed regarding for the tobacco smoking rate. The number of eosinophils was counted in all subjects. The relative expressive levels of IL-5 and IL-1RA were measured with ELISA in Bronchoalveolar lavage (BAL) and serum. RESULTS: The BAL levels of IL-5, IL-1ra, eosinophils and lymphocytes positively correlates with the rate of tobacco smoking in AEP patients (p < 0.005) comparing with those in healthy control groups. No significant association was observed between the serum levels IL-5 and IL-1ra and the rate of tobacco smoking in AEP patients (p > 0.05) comparing with those in healthy control groups. CONCLUSIONS: Smoking increases the BAL levels of IL-5 and IL-1RA, which is associated with the onset of AEP.

Systemic cytokine levels show limited correlation with risk of HIV-1 acquisition.

It has been hypothesized that immune activation and inflammation may increase HIV-1 susceptibility, and that cytokines may be useful biomarkers for risk. Within a prospective cohort, we conducted a nested case-control analysis of plasma cytokine levels among women who acquired HIV-1 <3 months after sampling, compared with 3 different control groups. We observed associations between lower interleukin (IL)-6 and IL-10 and higher IL-7 levels with HIV-1 acquisition, however, these associations were inconsistent when comparing with different control groups. Inconsistent results within our study and among previous studies suggest that reproducible findings are needed before cytokines are useful biomarkers for HIV-1 susceptibility.

Is alcoholic pancreatitis associated with enteroviral infection?

AIM: To investigate whether enteroviral infection might trigger acute pancreatitis in patients made susceptible due to high alcohol consumption. METHODS: Patients with alcohol-induced acute pancreatitis were analyzed for signs of simultaneous or preceding enteroviral infection. We studied the serum samples of 40 patients hospitalized for alcohol-induced acute pancreatitis and 40 controls recruited from an alcohol detoxification center. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus RNA and diagnose acute viremia. Immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) enteroviral antibodies were measured using enzyme immunoassay to detect subacute and previous infections. The samples were considered positive when the antibody titers were ≥ 15 IU. Furthermore, using RT-PCR, we studied pancreatic biopsy samples obtained during surgery from nine patients with chronic pancreatitis, one patient with acute pancreatitis and ten control patients with pancreatic carcinoma for evidence of persisting enteroviral RNA in the pancreatic tissue. RESULTS: No enterovirus RNA indicating acute viremia was detected by RT-PCR in the serum samples of any patient or control. A high incidence of positive antibody titers was observed in both study groups: IgM antibodies had positive titers in 5/40 (13%) vs 4/40 (10%), P = 0.723; IgG in 15/40 (38%) vs 19/40 (48%), P = 0.366; and IgA in 25/40 (63%) vs 33/40 (83%), P = 0.045, patients and controls, respectively. Ten (25%) patients had severe pancreatitis and two (5%) required treatment in intensive care. The median length of hospitalization was 7 d (range: 3-47 d). The severity of acute pancreatitis or the length of hospitalization was not associated with enteroviral IgM, IgG or IgA antibodies. Five pancreatic biopsy samples tested positive with RT-PCR, three (8%) in the control group and two (5%) in the patient group (P = 0.64). CONCLUSION: The rate of enteroviral infection is not increased in patients with alcohol-induced acute pancreatitis when compared to alcoholics with similar high alcohol use.

Soluble TRAIL in normal pregnancy and acute pyelonephritis: a potential explanation for the susceptibility of pregnant women to microbial products and infection.

OBJECTIVE: Pregnancy is characterized by activation of the innate immune response demonstrated by phenotypic and metabolic changes in granulocytes and monocytes. This state of activation has been implicated in the pathophysiology of multiorgan dysfunction of pregnant women with acute viral or bacterial infection. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the mediators responsible for neutrophil apoptosis. Gene deletion of TRAIL results in delayed neutrophil apoptosis and resolution of inflammation after the administration of bacterial endotoxin. The aim of this study was to determine whether maternal plasma concentrations of the soluble form of TRAIL (sTRAIL) differ in women with uncomplicated pregnancy and those with acute pyelonephritis. METHOD: A cross-sectional study was conducted to include women in the following groups: (1) non-pregnant (n = 23); (2) uncomplicated pregnancies (n = 93) and (3) pregnancies with acute pyelonephritis (n = 23). Plasma concentrations of sTRAIL were determined by enzyme-linked immunoassay. RESULTS: (1) Women with uncomplicated pregnancies had a lower mean plasma sTRAIL concentration (pg/mL) than non-pregnant women (31.5 ± 10.1 versus 53.3 ± 12.5; p < 0.001); (2) plasma sTRAIL concentrations did not change as a function of gestational age (Pearson correlation = -0.1; p = 0.4); (3) the mean plasma sTRAIL concentration (pg/mL) was significantly lower in pregnant women with acute pyelonephritis than in those with uncomplicated pregnancies (20.5 ± 6.6 versus 31.5 ± 10.1; p < 0.001) and (4) among patients with acute pyelonephritis, patients with bacteremia had a significantly lower mean plasma concentration of sTRAIL (pg/mL) than those without bacteremia (15.1 ± 4.8 versus 24.7 ± 4.6; p < 0.001). CONCLUSION: Women with uncomplicated pregnancies are associated with a significantly lower mean maternal plasma concentration of sTRAIL than that observed in non-pregnant women. Moreover, a further decrease in plasma sTRAIL concentration was observed in pregnant women with acute pyelonephritis, and this could account, at least in part, for the exaggerated intravascular inflammatory response previously reported in pyelonephritis during pregnancy.