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PURPOSE OF REVIEW: Infection with hepatitis E virus (HEV) is a global health concern, yet a clinically underdiagnosed cause of acute and chronic hepatitis. The WHO estimates that 20 million people are infected with HEV annually, yet the epidemiology, diagnosis and prevention remain elusive in many clinical settings. RECENT FINDINGS: Orthohepevirus A (HEV-A) genotypes 1 and 2 cause acute, self-limited hepatitis through faecal-oral transmission. In 2022, the first-ever vaccine campaign was implemented as a response to an HEV outbreak in an endemic region. HEV-A genotypes 3 and 4 are zoonotic infections that primarily cause chronic HEV infection in immunosuppressed populations. Pregnant women and immunocompromised persons are at high risk for severe illness in some settings. Another recent advance in our knowledge of HEV is the zoonotic transmission of Orthohepevirus C (HEV-C) to humans, presumably from contact with rodents and/or their excrement. Previously, HEV infection in humans was presumed to be limited to HEV-A only. SUMMARY: Clinical recognition and accurate diagnosis are essential to the management of HEV infection and understanding the global burden of the disease. Epidemiology affects clinical presentations. Targeted response strategies in HEV outbreaks are needed for the prevention of disease, and vaccine campaigns may prove to be an effective part of these strategies.
Subject(s)
Hepatitis E virus , Hepatitis E , Animals , Humans , Female , Pregnancy , Hepatitis E virus/genetics , Hepatitis E/diagnosis , Hepatitis E/epidemiology , Hepatitis E/prevention & control , Zoonoses/epidemiology , Disease Outbreaks , Acute DiseaseABSTRACT
BACKGROUND: Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated clinical and molecular features to identify those features unique to early-onset CRC that differentiate these patients from patients 50 years old or older. METHODS: Baseline characteristics were evaluated according to the CRC onset age with 3 independent cohorts. A fourth cohort was used to describe the impact of age on the consensus molecular subtype (CMS) prevalence. RESULTS: This retrospective review of more than 36,000 patients with CRC showed that early-onset patients were more likely to have microsatellite instability (P = .038), synchronous metastatic disease (P = .009), primary tumors in the distal colon or rectum (P < .0001), and fewer BRAF V600 mutations (P < .001) in comparison with patients 50 years old or older. Patients aged 18 to 29 years had fewer adenomatous polyposis coli (APC) mutations (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.35-0.90; P = .015) and an increased prevalence of signet ring histology (OR, 4.89; 95% CI, 3.23-7.39; P < .0001) in comparison with other patients younger than 50 years. In patients younger than 40 years, CMS1 was the most common subtype, whereas CMS3 and CMS4 were uncommon (P = .003). CMS2 was relatively stable across age groups. Early-onset patients with inflammatory bowel disease were more likely to have mucinous or signet ring histology (OR, 5.54; 95% CI, 2.24-13.74; P = .0004) and less likely to have APC mutations (OR, 0.24; 95% CI, 0.07-0.75; P = .019) in comparison with early-onset patients without predisposing conditions. CONCLUSIONS: Early-onset CRC is not only distinct from traditional CRC: special consideration should be given to and further investigations should be performed for both very young patients with CRC (18-29 years) and those with predisposing conditions. The etiology of the high rate of CMS1 in patients younger than 40 years deserves further exploration.
Subject(s)
Adenocarcinoma/epidemiology , Biomarkers, Tumor/genetics , Colorectal Neoplasms/epidemiology , Mutation , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adolescent , Adult , Age of Onset , Aged , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Mutational Analysis , Female , Follow-Up Studies , Humans , Incidence , Male , Microsatellite Instability , Middle Aged , Prognosis , Retrospective Studies , United States/epidemiology , Young AdultABSTRACT
For severe burn injuries, successful medical intervention is accomplished by rapidly and safely providing physical barriers that can cover damaged skin tissues, thereby preventing critical danger of extensive bleeding and infection. Despite availability of a large assortment of wound coverage options, the etiology of wound healing is rather complex leading to significant defects in skin repair. The use of cell-mediated treatment approaches in combination with bioengineered wound coverage constructs may provide the missing tool to improve wound healing outcomes. In this study, we have used an engineered 3D PEGylated fibrin (P-fibrin) gel as a scaffold for adipose derived stem cells (ASCs) delivery into the burn injury model. We were able to confirm the presence of ASCs in the wound site two weeks after the initial injury. Delivery of ASCs-containing gels was associated with improved vascularization of the injured area at early time points accompanied by an increased abundance of mannose receptor expressing cells. Moreover, the application of P-fibrin biomaterial exhibited positive effects on early mononuclear cell recruitment and granulation tissue formation without negatively affecting wound closure kinetics or extent of connective tissue deposition. Collectively, our data support the feasibility of using P-fibrin gels in wound dressing applications requiring controlled delivery of viable cells.
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BACKGROUND: SARS-CoV-2 vaccination induces a varied immune response among persons with chronic liver disease (CLD) and solid organ transplant recipients (SOTRs). We aimed to evaluate the humoral and T-cell-mediated immune responses to SARS-CoV-2 vaccination in these groups. METHODS: Blood samples were collected following the completion of a standard SARS-CoV-2 vaccination (2 doses of either BNT162b2 or mRNA-12732), and a subset of patients had a blood sample collected after a single mRNA booster vaccine. Three separate methods were utilized to determine immune responses, including an anti-spike protein antibody titer, neutralizing antibody capacity, and T-cell-mediated immunity. RESULTS: The cohort included 24 patients with chronic liver disease, 27 SOTRs, and 9 controls. Patients with chronic liver disease had similar immune responses to the wild-type SARS-CoV-2 compared with controls following a standard vaccine regimen and single booster vaccine. SOTRs had significantly lower anti-S1 protein antibodies (p < 0.001), neutralizing capacity (p < 0.001), and T-cell-mediated immunity response (p = 0.021) to the wild-type SARS-CoV-2 compared with controls following a standard vaccine regimen. Following a single booster vaccine, immune responses across groups were not significantly different but numerically lower in SOTRs. The neutralization capacity of the B.1.1.529 Omicron variant was not significantly different between groups after a standard vaccine regimen (p = 0.87) and was significantly lower in the SOTR group when compared with controls after a single booster vaccine (p = 0.048). CONCLUSION: The immunogenicity of the SARS-CoV-2 vaccine is complex and multifactorial. Ongoing and longitudinal evaluation of SARS-CoV-2 humoral and cellular responses is valuable and necessary to allow frequent re-evaluation of these patient populations.
Subject(s)
COVID-19 , Liver Diseases , Humans , COVID-19 Vaccines , SARS-CoV-2 , Transplant Recipients , BNT162 Vaccine , COVID-19/prevention & control , Vaccination , Immunity, CellularABSTRACT
BACKGROUND: A community-based, colorectal cancer (CRC) screening program for uninsured/underinsured individuals was successfully implemented in El Paso, Texas to increase CRC screening rates. Our aim was to determine the colorectal neoplasia prevalence among program participants and between screening groups. METHODS: We retrospectively reviewed participant records from 2012 to 2017. Average-risk patients were first screened with a fecal immunochemical test (FIT) and included if positive. Above average-risk patients due to a family history of CRC were referred directly for screening colonoscopy. Patients were excluded if experiencing melena or hematochezia or had a personal history of colon polyps or CRC. RESULTS: Of the 638 screening colonoscopies performed, 59.4% were in FIT-positive subjects and 40.6% were in subjects with a family history of CRC. Patients were predominantly female (72.9%), aged 50-65 years (84.2%), Hispanic (97.9%), and born in Mexico (92.4%). Overall, the detection rate for polyps, adenomas, and advanced adenomas was 46.2%, 34.3%, and 11.1%, respectively. Fifteen patients had adenocarcinoma (2.4%). Compared with colonoscopies in patients with a family history, FIT-positive patients demonstrated a higher prevalence of polyps (PR 1.39, 95% CI 1.09-1.78), adenomas (PR 1.55, 95% CI 1.15-2.07), advanced adenomas (PR 3.04, 95% CI 1.67-5.56). CONCLUSIONS: This community-based CRC screening program in an enriched cohort of predominantly Mexican Americans was effective in identifying colorectal neoplasia and cancer. Additionally, there was an increased prevalence of colorectal neoplasia in average-risk, FIT-positive patients undergoing screening colonoscopy compared with above average-risk patients with a family history of CRC. Similar screening programs would likely benefit at-risk populations.
Subject(s)
Adenoma , Colorectal Neoplasms , Adenoma/pathology , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Early Detection of Cancer/methods , Female , Hispanic or Latino , Humans , Male , Mass Screening/methods , Prevalence , Retrospective Studies , Texas/epidemiologyABSTRACT
Prior reports have associated the unusual presentations of anti-glomerular basement membrane (anti-GBM) disease and pulmonary aspergillosis in an immunocompetent host. We present the case of a previously healthy 24-year-old man who presented with symptoms of hemoptysis, cough, and dyspnea. His environmental risk factors included tobacco use (smoking), hydrocarbon exposure, and an unidentified mold present in his home. Laboratory evaluation revealed positive serum anti-GBM autoantibodies and positive detection of galactomannan in the bronchoalveolar lavage fluid. The diagnosis of anti-GBM disease was confirmed with a kidney biopsy. Management included therapy with voriconazole for aspergillosis and prednisone, plasmapheresis, and eventually cyclophosphamide for anti-GBM disease.
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Purpose: Colorectal cancers are classified as right/left-sided based on whether they occur before/after the splenic flexure, with established differences in molecular subtypes and outcomes. However, it is unclear if this division is optimal and whether precise tumor location provides further information.Experimental Design: In 1,876 patients with colorectal cancer, we compared mutation prevalence and overall survival (OS) according to side and location. Consensus molecular subtype (CMS) was compared in a separate cohort of 608 patients.Results: Mutation prevalence differed by side and location for TP53, KRAS, BRAFV600, PIK3CA, SMAD4, CTNNB1, GNAS, and PTEN Within left- and right-sided tumors, there remained substantial variations in mutation rates. For example, within right-sided tumors, RAS mutations decreased from 70% for cecal, to 43% for hepatic flexure location (P = 0.0001), while BRAFV600 mutations increased from 10% to 22% between the same locations (P < 0.0001). Within left-sided tumors, the sigmoid and rectal region had more TP53 mutations (P = 0.027), less PIK3CA (P = 0.0009), BRAF (P = 0.0033), or CTNNB1 mutations (P < 0.0001), and less MSI (P < 0.0001) than other left-sided locations. Despite this, a left/right division preceding the transverse colon maximized prognostic differences by side and transverse colon tumors had K-modes mutation clustering that appeared more left than right sided. CMS profiles showed a decline in CMS1 and CMS3 and rise in CMS2 prevalence moving distally.Conclusions: Current right/left classifications may not fully recapitulate regional variations in tumor biology. Specifically, the sigmoid-rectal region appears unique and the transverse colon is distinct from other right-sided locations. Clin Cancer Res; 24(5); 1062-72. ©2017 AACRSee related commentary by Dienstmann, p. 989.