Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.

Ostomy-Related Quality of Life in Puerto Ricans Living With Inflammatory Bowel Disease: A Prospective Cohort Study.

PURPOSE: The aim of this study was to determine ostomy-related quality of life (QOL) in Hispanic Puerto Ricans living with an enteral stoma and inflammatory bowel disease (IBD). We analyzed possible associations between QOL and sex, diagnosis, and type and duration of stoma. DESIGN: Prospective cohort study. SUBJECTS AND SETTINGS: The sample comprised 102 adults living with IBD and an ostomy; 60 of 101 (59.4%) were males, 44 of 102 (43.1%) had Crohn's disease, and 60 of 102 (58.9%) had an ileostomy. Participants were receiving care at the Center for IBD of the University of Puerto Rico in San Juan, Puerto Rico, between January 2012 and December 2014. METHODS: One-hundred two adults Puerto Ricans with IBD completed the Stoma Quality of Life (Stoma-QOL) questionnaire. Data were analyzed using frequency distributions for categorical variables and summary statistics for continuous variables. Independent-group t test and one-way analysis of variance, with the post hoc Tukey test, were used to determine group differences for the variables of age, sex, civil status, time living with an ostomy, type of ostomy, and IBD diagnosis. Results were analyzed according to the number of responses to each variable; the denominator varied for some variables. RESULTS: Having an ostomy for more than 40 months was significantly associated with a higher QOL score (59.0 vs 50.7; P = .05). Males had significantly higher scores than females (59.94 vs 50.23; P = .0019). Age, IBD diagnosis, and type of ostomy were not associated with the Stoma-QOL scores. CONCLUSIONS: The achievement (over 40 months) to attain improved ostomy-related QOL suggests that early training in the care of the ostomy and advanced planning when leaving home may enhance ostomy-related QOL. Lower QOL in women may represent an opportunity for a sex-specific educational intervention.

Rejection, Recurrence, or Something Else?

Since the introduction of liver transplant as treatment for end-stage liver disease, thousands of lives have been saved. To prevent organ rejection, immunosuppression is given chronically and hence, patients are at increased risk for opportunistic infections related to immunosuppression, especially within the first year after the transplant. However, opportunistic infections can occur years after the transplantation. Disseminated nocardiosis is one of these infections, and although the common presentation includes involvement of skin, lungs, and central nervous system. We present an uncommon presentation of nocardiosis in which cholestasis and elevated liver enzymes predominate, mimicking organ rejection and liver disease recurrence. Infectious etiologies, including opportunistic microorganisms, must always be ruled out in patients presenting elevation in liver enzymes and cholestasis after liver transplant as early diagnosis can prevent complications such as re-transplantation and even death.

Tackling the Health Challenge posed by Hepatitis C in Puerto Rico: A Call for Immediate Public Health Actions.

Within the past decade, researchers and hepatitis C specialists in Puerto Rico have highlighted the burden of hepatitis C and associated disease outcomes in the island to raise public awareness about this problem and set out a call to action to tackle prevention and control efforts, yet so far no concrete actions have taken place. The population-based studies on hepatitis C have documented that the main risk factor is the sharing of syringes and drug paraphernalia to inject drugs, that most seropositive individuals are unaware of their infection status, and that there are large knowledge deficits about the disease, its risk factors, and measures of prevention and control. The subject is further complicated by the fact that despite hepatitis C reporting is mandatory, there is no effective epidemiological surveillance system to provide the information needed for planning, implementation, monitoring, and evaluation of intervention strategies for this infection and access to medical and other existing therapies is limited. This document addresses the disparities in HC V infection and its adverse outcomes experienced among Puerto Ricans and attempts to set out strategies to address a public health response for hepatitis C at the meso and macro levels of the social-ecological model. Diverse organizations and major stakeholders are urged to mount an adequate response to hepatitis C by transforming current scientific evidence into public health actions to increase awareness, identify those who are actively infected, and link infected individuals into comprehensive care and treatment.

Presence of tissue transglutaminase IgA antibody as a celiac disease marker in a sample of patients with irritable bowel syndrome.

Recent medical literature agrees that celiac disease (CD) is much more prevalent in western civilization than it was thought to be in the past. Given the potential complications and consequences of untreated CD, screening programs have been considered. Symptoms of celiac disease may resemble those of Irritable Bowel Syndrome. A group of patients with IBS was screened for CE using the Tissue Transglutaminase Antibody IgA serum test. A total of 18 patients were screened. All of our patients tested negative for TTG IgA. This finding may indicate that the prevalence of CD may be low in our population. Further population studies are needed to confirm our finding.

Liver transplantation for hepatocellular carcinoma in Puerto Ricans: underutilization of a curative therapy.

OBJECTIVE: Hepatocellular carcinoma (HCC), the most common type of liver cancer, is becoming a healthcare burden for Puerto Rico and, in particular, for those clinics that specialize in liver disease. It is our hypothesis that liver transplantation, the most effective curative option for unresectable tumors, is underutilized. We describe in detail the outcomes of liver transplants for HCC in Puerto Ricans referred to a major liver transplant center in the USA. METHODS: Thirty-two Puerto Rican HCC patients receiving transplants (from January 1, 1997, through July of 2012) at Tampa General Hospital are described. Recurrence rates were calculated, and the Kaplan-Meier estimator was used for survival analysis. RESULTS: The proportion of transplants performed for HCC in our Puerto Rican patients was only 12% (p = 0.05). Disease-free survival at 1, 3, and 5 years was 93.7%, 83%, and 78.8%, respectively. Patient survival at 1, 3, and 5 years was 96.7%, 75%, and 67%, respectively. Sixty-nine percent of the 32 patients were alive at the mean follow-up of 56 months. The recurrence rate from 2002 to the present is 14%. CONCLUSION: This study provides the most comprehensive report detailing the relative benefits of utilizing liver transplantation as a curative option for Puerto Ricans with hepatocellular carcinoma. It also incorporates the first comprehensive review of the available literature of liver cancer in Puerto Rico. Survival and recurrence rates were comparable to published results. In Puerto Rico, liver transplantation for HCC patients has been underutilized. In order to improve outcomes over the next 2 decades, it is imperative that the healthcare system in Puerto Rico handle the burden of this disease using liver transplantation, locoregional therapies, and newer treatments for hepatitis C and HCC.

Profile of the average organ non-donor: can it be used predictively?

OBJECTIVE: To describe the profile of the average organ non-donor, compare it to that of the average donor, and identify characteristics that predict the likelihood that a given individual will be a non-donor. METHODS: The charts of 397 consenting potential organ donors of LifeLink of Puerto Rico from 2009 through 2011 were reviewed. Data regarding gender, age, BMI, the presence of diabetes, hypertension and/or kidney injury, death from cerebrovascular accident, and smoking were collected. RESULTS: Of the 397 charts reviewed, 283 were from donors, 96 were from non-donors, and 18 were excluded from the analysis. When compared to donors, non-donors were found more frequently to be 60 years old or older, diabetic, hypertensive, or obese; to have suffered from kidney injury, to have smoked and to have died of a cerebrovascular accident. On multivariate analysis, age, diabetes, kidney injury and smoking remained significant. However, after adjusting for age, only smoking and death from cerebrovascular accident remained statistically associated to non-donor status. CONCLUSION: Although being over 60 years old, having smoked and dying from a cerebrovascular accident were characteristics found significantly more frequently in non-donors, these characteristics were also present in some donors. Therefore, a careful evaluation of each potential donor is still mandatory to avoid the loss of transplantable organs.

Demographics, clinical characteristics, IFNL3- and IFNL4- polymorphisms in a cohort of hepatitis C patients from Puerto Rico.

OBJECTIVE: To describe the risk factors for infection, complications, treatment received and response in Puerto Ricans with HCV attending gastroenterology clinics at UPR-MSC, and the prevalence of single nucleotide polymorphisms (SNPs) in IFNL3 and IFNL4 in this population. METHODS: After consent, demographic and medical data were obtained and blood samples were drawn from each patient. The QIAamp Blood-Maxi Kit was employed for DNA extraction. The TaqMan allelic discrimination assay was employed for SNP genotyping. HCV-RNA was measured by branched-chain DNA assay. Frequency distributions were used to describe the study population and the prevalence of SNPs. The UPR Medical Sciences Campus IRB approved the study. RESULTS: Of 259 patients recruited, 64% were men. Genotype 1was found in 112/136 (82%). Of 150 subjects treated, 19% had sustained virological response (SVR), 40% received treatment with pegylated interferon plus ribavirin. The SNP frequencies (n = 239) of IFNL3 locus rs12979860 were 27% (C/C), 50% (C/T), and 23% (T/T), and for rs8099917 were 46% (T/T), 47% (T/G), and 7% (G/G). SNP frequencies of IFNL4 locus ss469415590 were 26% (TT/TT), 48% (TT/ΔG), and 26% (ΔG/ΔG). CONCLUSION: HCV-infected Hispanics in our sample (all of which were Puerto Rican) were shown to have a low SVR rate of 19%. The demographic characteristics were similar to those of other study groups in the US, except for the annual income. Genotype-1 was the most prevalent in those patients with known HCV genotypes. This study group showed significant differences with frequencies observed in other populations. Lower frequencies of the favorable genotypes were found in our group compared with the populations having European and Asian ancestry.

Prevalences of Hypertension, Type 2 Diabetes Mellitus, and Cardiovascular Disease in a Cohort of Puerto Ricans with Non-alcoholic Fatty Liver Disease.

BACKGROUND & OBJECTIVES: Patients with non-alcoholic fatty liver disease (NAFLD) have high prevalences of hypertension (HTN), type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD), and vice versa. The mechanism of this development is unknown but appears to be related to an underlying metabolic derangement that affects multiple organs. This study aimed to determine the prevalences of these conditions in patients with diagnosed NAFLD. METHODS: Our cohort study aimed to determine the prevalences of HTN, T2DM, and CVD in NAFLD patients registered in the liver database of the University of Puerto Rico School of Medicine; this information is recorded in their medical records. Patients whose liver disease had a different etiology were excluded. The study was approved by the UPR Medical Sciences Campus Institutional Review Board. RESULTS: Our final sample consisted of 141 NAFLD patients; 64.5% (n = 91) of them were females. The average age was 69 (±10.2 years). The prevalences of HTN, T2DM, and CVD were 53.9%, 57.5%, and 7.8%, respectively. In patients with NAFLD, there was a significant association between T2DM and being 65 years old or older (P < 0.001). CONCLUSION: Our data indicate that HTN and T2DM are highly prevalent in NAFLD patients in PR; however, CVD prevalence was lower than expected. Additional, studies are required to further define the associations. We recommend metabolic condition screening for all NAFLD patients.

The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer-BioNTech Vaccine.

The aim of this study was to analyze the profiles of IgG subclasses in COVID-19 convalescent Puerto Rican subjects and compare these profiles with those of non-infected immunocompetent or immunocompromised subjects that received two or more doses of an mRNA vaccine. The most notable findings from this study are as follows: (1) Convalescent subjects that were not hospitalized developed high and long-lasting antibody responses. (2) Both IgG1 and IgG3 subclasses were more prevalent in the SARS-CoV-2-infected population, whereas IgG1 was more prevalent after vaccination. (3) Individuals that were infected and then later received two doses of an mRNA vaccine exhibited a more robust neutralizing capacity against Omicron than those that were never infected and received two doses of an mRNA vaccine. (4) A class switch toward the "anti-inflammatory" antibody isotype IgG4 was induced a few weeks after the third dose, which peaked abruptly and remained at high levels for a long period. Moreover, the high levels of IgG4 were concurrent with high neutralizing percentages against various VOCs including Omicron. (5) Subjects with IBD also produced IgG4 antibodies after the third dose, although these antibody levels had a limited effect on the neutralizing capacity. Knowing that the mRNA vaccines do not prevent infections, the Omicron subvariants have been shown to be less pathogenic, and IgG4 levels have been associated with immunotolerance and numerous negative effects, the recommendations for the successive administration of booster vaccinations to people should be revised.

Knowledge of and attitudes toward organ donation: a survey of medical students in Puerto Rico.

OBJECTIVE: The increasing demand for organ transplants exceeds the organ donation rate. Addressing this discrepancy is challenging for organ procurement agencies and health professionals involved in the care of patients in dire need of organs. Research suggests that health-care professionals' knowledge of, attitudes toward, and behavior in terms of organ donation and transplantation are deciding variables in promoting organ donation. In Puerto Rico, there is a lack of information regarding medical student's knowledge of and/or attitudes toward organ donation, a lack that our study was designed to address. METHODS: Two hundred thirty participants (98 first-year, 45 second-year, and 87 third-year medical students) completed a questionnaire consisting of 55 questions; 10 questions assessed knowledge and 20, attitudes about organ and tissue donation. The remaining questions inquired after demographic information, history of blood donation, and educational experience. RESULTS: In terms of their knowledge about organ donation, the participating students had a mean score of 6.29 on a 10-point scale-with 10 being the highest possible knowledge score-and 45.7% of them scored 7 or more. These data also showed that participants had a positive attitude toward organ donation (44.9; range 14 to 56), with approximately 72% having a favorable view. However, while 40% of the participating students stated their intentions to donate their organs, only 23% of them had donor cards. CONCLUSION: We determined that medical students have a positive attitude towards organ donation. However, a substantial lack of knowledge of organ donation among our subjects is a barrier to their taking the necessary measures to become active donors. Our data highlight the need to incorporate educational programs to increase knowledge and awareness regarding organ donation and the transplantation process.

Differences in prevalence of inflammatory bowel disease in Puerto Rico between commercial and government-sponsored managed health care insured individuals.

BACKGROUND: Evaluation of ethnic and racial patterns of Inflammatory Bowel Disease (IBD) has demonstrated a higher incidence of IBD in Jews, and lower rates in blacks and Hispanics when compared to whites. There is limited data describing incidence and prevalence among Hispanics, the fastest growing minority in the United States. METHODS: To estimate the prevalence of IBD computerized records of all physicians billing and hospital discharges classified with ICD-9-CM IBD related codes were searched. Prevalence was estimated by age group, sex, and type of insurance (commercial versus government-sponsored managed care). RESULTS: Of 1,248,993 insured individuals in 2005, 186 had a diagnosis of Crohn's disease and 291 of ulcerative colitis. The estimated prevalence per 100,000 was 14.9 for Crohn's disease, 23.3 for ulcerative colitis, and 38.2 cases for IBD. The most significant difference was found when comparing insurance type, with a total IBD prevalence rate of 61.75 cases among commercial versus 14.36 cases among government-sponsored insured. CONCLUSIONS: The prevalence of IBD in this insured population in Puerto Rico places it among the highest described in a Hispanic population. Given the continued rise in prevalence of IBD and the limited studies describing the epidemiology of IBD in Hispanics, further studies which may provide important clues to the etiology of the disease as well as valuable information for appropriate health care planning are important.

Gynecologic Conditions in a Cohort with Inflammatory Bowel Disease: A Descriptive Analysis.

OBJECTIVE: Past studies have demonstrated that women with inflammatory bowel disease (IBD) have a higher risk of gynecological conditions than do women without it. We aimed to characterize the gynecological histories of Hispanic Women living in Puerto Rico with IBD. METHODS: We identified women, aged 21 to 55 years, with a confirmed IBD diagnosis and receiving follow-up care from the University of Puerto Rico IBD clinics from 2017 through 2020. A questionnaire was administered to acquire sociodemographics, family history, past medical history, IBD diagnosis, and gynecologic aspects. RESULTS: One hundred eighty-six women were recruited. Fifty-three (28%) patients had ulcerative colitis, while 133 (72%) had Crohn's disease. Fifty-six percent of all the participants had a chronic illness in addition to than their IBD. Seventy-four out of 186 patients reported having had at least 1 late period within the last 12 months. Fifty-three (28%) described their period patterns as irregular. Thirty-nine (21%) of the patients reported having been vaccinated against human papillomavirus (HPV), and 8 (4%) had been infected by it. Nine out of 186 (5%) patients reported suffering from infertility. CONCLUSION: The results showed that our Hispanic patients (living in Puerto Rico) had a prevalence of irregular menstrual cycles that was similar to that observed in other populations. On the other hand, the presence of HPV, infertility, and cervical cancer were lower and the frequency of Papanicolaou smears performed higher than what has been seen in the continental United States, suggesting that this topic should be investigated in future studies.

A Survey of Cannabis Use among Patients with Inflammatory Bowel Disease (IBD).

Inflammatory bowel diseases (IBDs) are chronic conditions of unknown cause or cure. Treatment seeks to reduce symptoms and induce and maintain remission. Many patients have turned to alternatives, such as cannabis, to alleviate living with IBD. This study reports the demographics, prevalence, and perception on cannabis use of patients attending an IBD clinic. Patients agreed to participate and completed an anonymous survey during their visit or online. Descriptive analysis, Fisher's exact test, and Wilcoxon-Mann-Whitney rank-sum test were used. One hundred and sixty-two adults (85 males, 77 with CD) completed the survey. Sixty (37%) reported use of cannabis, of which 38 (63%) used it to relieve their IBD. A value of 77% reported low to moderate knowledge about cannabis, and 15% reported little to no knowledge. Among cannabis users, 48% had discussed use with their physician, but 88% said they would feel comfortable discussing medical cannabis for IBD. Most saw improvement of their symptoms (85.7%). A considerable number of patients with IBD use medical cannabis for their disease, unknown to their physician. The study reinforces the importance that physicians understand the role of cannabis in the treatment of IBD in order to appropriately counsel patients.

DietaAnti-Inflamatoria or DAIN: A Crohn's disease management strategy tailored for Puerto Ricans.

Diet has been increasingly shown to be of therapeutic benefit for patients with inflammatory bowel diseases (IBD), especially Crohn's disease (CD). Yet dietary guidelines are nonexistent. Moreover, diets tailored to Puerto Ricans with IBD living on the island, have not been developed and tested. The rising prevalence of IBD in Puerto Rico warrants exploring the use of diet as part of the treatment strategies for these patients [1]. Here, we describe the study design of "Dieta Anti-Inflamatoria" or DAIN, a parallel two-arm randomized pilot trial aiming at testing the efficacy of IBD-Anti-inflammatory diet (IBD-AID) adapted for adults with CD living in Puerto Rico (clinical trial registration number: NCT05627128). We tailored the IBD-AID to the local cuisine preferences and food availability by creating and adapting recipes consistent with the IBD-AID principles [2,3]. In focus groups with a Community Research Advisory Panel and one-on-one consultations with implementation experts, we identified several aspects of the intervention to adapt before the implementation. The objectives of the stakeholder/expert-informed adaptation were to improve feasibility and compliance while developing the culturally tailored dietary intervention. DAIN was designed for adults living in Puerto Rico with CD and geared to be affordable, appropriate, and acceptable for patients with mild-to-moderate CD. The significance of this work is the validation of culturally appropriate nutritional guidelines to help manage CD symptoms. DAIN provides a blueprint for a comprehensive nutritional program that can be adapted to regional preferences and local food availability allowing wider implementation of diet as an adjunct treatment in diverse clinical settings.

Factors contributing to health disparities in liver transplantation in a Hispanic population.

OBJECTIVE: Among the challenges that Puerto Rico transplant patients face are a lack of social support that would enable them to move away from Puerto Rico, the difficulty of obtaining insurance coverage, and limitations imposed by language barriers. These factors may lead to reduced access to liver transplantation, which is a form of healthcare disparity. The objective of the study is to describe a group of Puerto Rican liver transplant candidates for the first time and to determine whether the above-named factors limit the possibilities of these candidates to be listed for transplant. METHODS: Using non-public databases from the referral and the transplant center, we performed a retrospective analysis of the medical records of patients who had been evaluated for liver transplant candidacy. Candidates (137) from the Liver Transplant Clinic at the University of Puerto Rico School of Medicine pre-evaluated for transplant candidacy during the period of 2002 to 2008 were selected. RESULTS: Records from 86 men and 51 women were reviewed. The most predominant etiologies of liver disease were hepatitis C virus (36%), a combination of etiologies (26%), alcoholic liver disease (16%), and cryptogenic cirrhosis (10%). While social support and history of psychiatric disorders did not affect listing, private insurance increased the odds of being enlisted for liver transplant (OR = 2.97) 195%CI: 1.067-8.242) (p<0.05). CONCLUSION: Access to private insurance increases the possibility of patient's being enlisted for liver transplantation. Recommendations for overcoming the gap in access to transplants by patients without private insurance are discussed.

Increase in the number of IBD surgical resections at the Puerto Rico Medical Center: A brief report.

OBJECTIVE: There is limited data describing Inflammatory Bowel Disease (IBD) among Hispanics. In Puerto Rico, three studies have been conducted that estimate the prevalence of this disease. Although still rare, these studies coincide that IBD has increased during the last decades. This study aims to describe the IBD surgical resections received in the Pathology Laboratory of the Puerto Rico Medical Center (PRMC) in two periods: 1966-82 and 2002-2008. METHODS: A retrospective review of the Surgical Pathology reports was done. A total of 133 reports complied with the inclusion criteria for IBD out of a total of 314,493 pathologies evaluated. For purposes of comparison, the data was grouped into 3 time periods: 1966-1973, 1974-1982 and 2002-08. RESULTS: The number of IBD cases per 100,000 pathologies for the period 1966-73 was 15.1, for the period 1974-82 was 19.1 and for the period 2002-08 was 125.0. The number of IBD resections increased 87.9% when comparing years 1966-73 with 2002-2008, with similar increases in Ulcerative Colitis and Crohn's Disease. Although this result was not statistically significant (p>0.05), a higher proportion of IBD patients had an IBD resection at a younger age in the 2002-2008 time period. A change in the sex profile of the patients was also identified; the majority of cases (75%) were females in the years 1966-1973 while 50.6% were males in 2002-2008. CONCLUSION: Our results confirm an increase in IBD surgical resections at the PRMC. Although not significant, a higher proportion of incident cases are occurring among younger age groups and the distribution of incident cases has become similar between males and females in recent years.

Inefficient Induction of Neutralizing Antibodies against SARS-CoV-2 Variants in Patients with Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy after Receiving a Third mRNA Vaccine Dose.

Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose can neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)]. Fifty-six subjects with IBD and 12 healthy subjects were recruited. Ninety percent of patients with IBD (49/56) received biologics and/or immunomodulatory therapy. Twenty-four subjects with IBD did not develop effective neutralizing capability against the Omicron variant. Seventy percent (17/24) of those subjects received anti-tumor necrosis factor therapy [10 = adalimumab, 7 = infliximab], two of which had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and more extensive studies are needed to evaluate optimal immunity.

Clinical differentiation of inflammatory bowel disease (IBD) in Latin America and the Caribbean.

ABSTRACT: The aim of the present study was to describe the epidemiological and clinical characteristics of inflammatory bowel disease (IBD), including medical and surgical treatments, in several countries in Latin America and the Caribbean.IBD is recognized as a global health problem because its incidence and prevalence have increased significantly over the last few years.This multicenter retrospective cohort study included 4714 patients with IBD diagnosed from 9 countries in Latin America and the Caribbean: Colombia, Cuba, Dominican Republic, Ecuador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela.Crohn disease (CD) was more frequent in Puerto Rico (71.9%), the Dominican Republic (61.0%), and Peru (53.1%). Ulcerative colitis was more frequent in Colombia (78.6%), Venezuela (78.2%), Mexico (75.5%), Cuba (69.9%), Ecuador (64.1%), and Uruguay (60.9%). The following clinical characteristics were more frequent in the Caribbean: penetrating behavior in CD, steroid dependence, steroid resistance, intolerance to thiopurines, extraintestinal manifestations, surgeries, hospitalizations due to IBD, and family history of IBD. The factors associated with the use of biological therapy were pancolitis in ulcerative colitis, penetrating behavior in CD, steroid resistance and dependence, presence of extraintestinal manifestations, and the need for surgery.This study from Latin America and the Caribbean demonstrated the different epidemiological and clinical characteristics of IBD.

Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity and inflammation due to dysregulated immunometabolism.

Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking. The mechanism for Crohn's disease-like inflammation, lung fibrosis, and macrophage lipid accumulation in these patients remains enigmatic. The aim of this study is to understand the cellular basis of inflammation in HPS-1. We performed mass cytometry, proteomic and transcriptomic analyses to investigate peripheral blood cells and serum of HPS-1 patients. Using spatial transcriptomics, granuloma-associated signatures in the tissue of an HPS-1 patient with granulomatous colitis were dissected. In vitro studies were conducted to investigate anti-microbial responses of HPS-1 patient macrophages and cell lines. Monocytes of HPS-1 patients exhibit an inflammatory phenotype associated with dysregulated TNF, IL-1α, OSM in serum, and monocyte-derived macrophages. Inflammatory macrophages accumulate in the intestine and granuloma-associated macrophages in HPS-1 show transcriptional signatures suggestive of a lipid storage and metabolic defect. We show that HPS1 deficiency leads to an altered metabolic program and Rab32-dependent amplified mTOR signaling, facilitated by the accumulation of mTOR on lysosomes. This pathogenic mechanism translates into aberrant bacterial clearance, which can be rescued with mTORC1 inhibition. Rab32-mediated mTOR signaling acts as an immuno-metabolic checkpoint, adding to the evidence that defective bioenergetics can drive hampered anti-microbial activity and contribute to inflammation.