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PURPOSE OF REVIEW: Microscopic colitis is an inflammatory disease of the colon that presents as watery diarrhea with minimal to normal endoscopic changes on colonoscopy. It encompasses two common subtypes, lymphocytic colitis and collagenous colitis, which are both treated similarly.Immune checkpoint inhibitor colitis is among the most common immune-related adverse events. Endoscopic and histological findings range from normal colonic mucosa to inflammatory bowel like changes. This review article provides update in treatment and management of microscopic colitis and immune checkpoint inhibitor colitis (ICPi colitis). RECENT FINDINGS: Recent studies on microscopic colitis have focused on the successful use of immunomodulators such as biologics for treatment of budesonide refractory microscopic colitis cases. Microscopic colitis does not confer an added risk for colorectal cancer.With the increasing usage of immunotherapy agents, immune checkpoint inhibitor colitis is becoming more common. ICPi colitis can be successfully managed with steroids, with treatment stepped up to biologics for moderate to severe cases or for mild cases that do not respond to steroids. Immunotherapy agents can be carefully re-introduced in mild cases, after treatment of ICPi colitis. SUMMARY: Biologics can be used to treat budesonide refractory microscopic colitis. ICPi colitis can be managed with steroids and biologics in moderate to severe cases.
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Produtos Biológicos , Colite Microscópica , Colite , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Colite Microscópica/tratamento farmacológico , Colite Microscópica/patologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Diarreia/tratamento farmacológico , Diarreia/etiologia , Colonoscopia , Budesonida/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
INTRODUCTION: Colorectal cancer (CRC) incidence and mortality rates are increasing in adults aged <50 years. Young-onset adenoma (YOA)-adenoma detected in adults younger than 50 years-may signify increased CRC risk, but this association has not been widely studied. Our aim was to compare the risk of incident and fatal CRC in adults aged <50 years with YOA diagnosis compared with those with a normal colonoscopy. METHODS: We conducted a cohort study of US Veterans aged 18-49 years who received colonoscopy between 2005 and 2016. The primary exposure of interest was YOA. Primary outcomes included incident and fatal CRC. We used Kaplan-Meier curves to calculate cumulative incident and fatal CRC risk and Cox models to examine relative CRC risk. RESULTS: The study cohort included 54,284 Veterans aged <50 years exposed to colonoscopy, among whom 13% (n = 7,233) had YOA at start of follow-up. Cumulative 10-year CRC incidence was 0.11% (95% confidence interval [CI]: 0.00%-0.27%) after any adenoma diagnosis, 0.18% (95% CI: 0.02%-0.53%) after advanced YOA diagnosis, 0.10% (95% CI: 0.00%-0.28%) after nonadvanced adenoma diagnosis, and 0.06% (95% CI: 0.02%-0.09%) after normal colonoscopy. Veterans with advanced adenoma had 8-fold greater incident CRC risk than those with normal colonoscopy (hazard ratio: 8.0; 95% CI: 1.8-35.6). Across groups, no differences in fatal CRC risk were observed. DISCUSSION: Young-onset advanced adenoma diagnosis was associated with 8-fold increased incident CRC risk compared with normal colonoscopy. However, cumulative CRC incidence and mortality at 10 years among individuals with either young onset non-advanced or advanced adenoma diagnosis were both relatively low.
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Adenoma , Neoplasias Colorretais , Adulto , Humanos , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Colonoscopia , Risco , Incidência , Adenoma/diagnóstico , Adenoma/epidemiologia , Detecção Precoce de Câncer , Fatores de RiscoRESUMO
BACKGROUND & AIMS: The incidence and mortality of early-onset colorectal cancer (CRC) are increasing. Adenoma detection, removal, and subsequent endoscopic surveillance might modify risk of CRC diagnosed before age 50 years (early-onset CRC). We conducted a systematic review of young-onset adenoma (YOA) prevalence, associated risk factors, and rate of metachronous advanced neoplasia after YOA diagnosis. METHODS: We performed a systematic search of multiple electronic databases through February 12, 2019 and identified studies of individuals 18 to 49 years old that reported prevalence of adenoma, risk factors for adenoma, and/or risk for metachronous advanced neoplasia. Summary estimates were derived using random effects meta-analysis, when feasible. RESULTS: The pooled overall prevalence of YOA was 9.0% (95% CI, 7.1%-11.4%), based on 24 studies comprising 23,142 individuals. On subgroup analysis, the pooled prevalence of YOA from autopsy studies was 3.9% (95% CI, 1.9%-7.6%), whereas the prevalence from colonoscopy studies was 10.7% (95% CI, 8.5%-13.5). Only advancing age was identified as a consistent risk factor for YOA, based on 4 studies comprising 78,880 individuals. Pooled rate of metachronous advanced neoplasia after baseline YOA diagnosis was 6.0% (95% CI, 4.1%-8.6%), based on 3 studies comprising 1493 individuals undergoing follow-up colonoscopy, with only 1 CRC case reported. Overall, few studies reported metachronous advanced neoplasia and no studies evaluated whether routine surveillance colonoscopy decreases risk of CRC. CONCLUSIONS: In a systematic review, we estimated the prevalence of YOA to be 9% and to increase with age. Risk for metachronous advanced neoplasia after YOA diagnosis is estimated to be 6%. More research is needed to understand the prevalence, risk factors, and risk of CRC associated with YOA.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Adenoma/epidemiologia , Adolescente , Adulto , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
Neuroinflammation and reactive oxygen species are thought to mediate the pathogenesis of Alzheimer's disease (AD), suggesting that mild cognitive impairment (MCI), a prodromal stage of AD, may be driven by similar insults. Several studies document that hypoxia-inducible factor 1 (HIF-1) is neuroprotective in the setting of neuronal insults, since this transcription factor drives the expression of critical genes that diminish neuronal cell death. HIF-1 facilitates glycolysis and glucose metabolism, thus helping to generate reductive equivalents of NADH/NADPH that counter oxidative stress. HIF-1 also improves cerebral blood flow which opposes the toxicity of hypoxia. Increased HIF-1 activity and/or expression of HIF-1 target genes, such as those involved in glycolysis or vascular flow, may be an early adaptation to the oxidative stressors that characterize MCI pathology. The molecular events that constitute this early adaptation are likely neuroprotective, and might mitigate cognitive decline or the onset of full-blown AD. On the other hand, prolonged or overwhelming stressors can convert HIF-1 into an activator of cell death through agents such as Bnip3, an event that is more likely to occur in late MCI or advanced Alzheimer's dementia.
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Disfunção Cognitiva/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Animais , Apoptose , Circulação Cerebrovascular , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MemóriaRESUMO
BACKGROUND: Asthma mortality and morbidity are higher in black than in white children. Fractional exhaled nitric oxide (FeNO) is a noninvasive biomarker of eosinophilic airway inflammation. Identification of differences in the effect of environmental tobacco smoke (ETS) on airway inflammation by race and ethnicity from a large sample is needed. OBJECTIVE: To estimate a racial difference in association with ETS and FeNO. METHODS: Data from the 2007 to 2012 National Health and Nutrition Examination Survey were analyzed to compare associations of ETS and FeNO levels in US black and other children. No ETS exposure was defined as a serum cotinine level lower than 0.05 ng/mL and ETS exposure was defined as a serum cotinine level of at least 0.05 ng/mL. FeNO was measured using a device that relies on an electrochemical sensor. Analyses took the complex survey design into account. RESULTS: The analytic sample was formed by 5,473 participants (6-11 years old, n = 2,385; 12-19 years old, n = 3,088) with complete data on demographics, serum cotinine levels, and 2 reproducible FeNO measurements. In weighted linear regression analyses at 6 to 11 years, the interaction term for ETS and black race was not significant (P = .15). At 12 to 19 years, the interaction term was significant (P = .03) in an analysis of all racial groups. In race-specific models, the coefficient for ETS exposure in blacks was -0.033 and that in others was -0.175, ie, ETS exposure was associated with a greater decrease in FeNO in non-blacks than in blacks. CONCLUSION: There was no evidence at 6 to 11 years of age for an effect modification by race of the association between ETS and FeNO. At 12 to 19 years, the data suggested an effect modification.
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Óxido Nítrico/metabolismo , Eosinofilia Pulmonar/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Biomarcadores/metabolismo , Criança , Etnicidade , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/metabolismo , Grupos Raciais , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: To evaluate the contemporary outcome of femoral-popliteal bypass compared with angioplasty and stenting in patients with symptomatic peripheral arterial disease (PAD) in terms of patency and reintervention rates. METHODS: We identified all patients evaluated at the Johns Hopkins Bayview Medical Center with the presumptive diagnosis of PAD from September 2005 to September 2010. In this group, we selected all symptomatic patients after failing medical management who received percutaneous transluminal angioplasty/stenting of the superficial femoral artery or femoral-popliteal bypass. We compared the overall patency and reintervention rates between the two groups as well as patency within TransAtlantic Inter-Society Consensus (TASC) II subgroups. Descriptive analyses were performed using χ(2) and two-sided t-tests. The Mann-Whitney U test was used to compare distributions of continuous variables and the Fisher exact test for categorical variables. Cox proportional hazard model was used to examine the treatment effect within each lesion type, using bypass as the reference group. RESULTS: Out of 1237 patients evaluated at Johns Hopkins Bayview Medical Center for PAD from September 2005 to September 2010, we identified 104 symptomatic patients who received percutaneous transluminal angioplasty/stenting of the superficial femoral artery or femoral-popliteal bypass after failing medical management. There were 61 male patients (56%), and the mean age was 68 years in both groups. Both treatment groups had similar risk factors. Overall, 77% of patients with TASC II A and B lesions underwent angioplasty and stenting, whereas 73% of patients with TASC C and D lesions underwent bypass (P < .01). The primary patency at 24 months was better for the stent group 67% (95% confidence interval [CI], 0.52-0.78) vs bypass group 49% (95% CI, 0.32-0.64; P = .05). The rate of reintervention within the 2-year period was higher in the bypass group compared with the stent group (54% vs 31%; P = .02). TASC A and B lesions combined demonstrated a reduced hazard of patency failure compared with TASC C or D lesions combined (hazard ratio, 2.42; 95% CI, 1.26, 4.65; P < .01). CONCLUSIONS: This is the first study that documents higher reintervention rates for femoral-popliteal bypass compared with angioplasty and stenting. We believe that the main reason for this finding is the fact that the bypass patients had significantly more advanced disease. This, emphasizes that one must consider the patient population undergoing intervention when comparing revascularization procedures. A prospective randomized trial is needed to determine the overall better treatment option.
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Angioplastia com Balão/instrumentação , Artéria Femoral/cirurgia , Doença Arterial Periférica/terapia , Enxerto Vascular , Veias/transplante , Idoso , Angioplastia com Balão/efeitos adversos , Baltimore , Implante de Prótese Vascular , Distribuição de Qui-Quadrado , Feminino , Artéria Femoral/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/terapia , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Enxerto Vascular/efeitos adversos , Grau de Desobstrução VascularRESUMO
OBJECTIVE: While patient eligibility for carotid artery stenting (CAS) is well established, the intraoperative technique remains widely varied. The decision to perform poststent ballooning (PSB) is operator-dependent and often influenced by the interpretation of poststent angiography. While visually creating a greater luminal diameter, it is unclear whether PSB has immediate risks or long-term benefits. The purpose of this report is to determine whether PSB has any effects on periprocedural hemodynamic stability. METHODS: A retrospective analysis of all patients that underwent CAS between 2005 and 2012 at a tertiary care center was performed. The primary end point was hemodynamic instability, defined as bradycardia (a heart rate of <60 beats/min) or hypotension (systolic blood pressure of <90 mm Hg) during the intraoperative or postoperative period. Binary logistic regression model was performed to determine the effect of PSB on the occurrence of hemodynamic instability, adjusting for patient's age, sex, hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, recent myocardial infarction, previous carotid endarterectomy, high-risk status, and symptomatic status. RESULTS: A total of 103 (51 men and 52 women) patients underwent placement of a unilateral carotid stent between 2005 and 2012 at our institution. All patients underwent prestent dilatation. However, 70% (n = 72) underwent PSB whereas 30% (n = 31) did not. PSB was a significant predictor of hemodynamic depression (odds ratio [OR], 3.8; 95% confidence interval, 1.3-11; P < .01). Symptomatic status, recent myocardial infarction, hyperlipidemia, and coronary artery disease were associated with a length of stay exceeding 24 hours postoperatively (OR, 6.6; P < .01, OR, 6.1; P < .01, OR, 5.4; P = .04, and OR, 9.3; P < .01, respectively). At follow-up, 97% (83/86) stents were patent. Two stent stenoses occurred in the group that received PSB, while one stent stenosis occurred in the group that did not receive PSB. CONCLUSIONS: PSB increases the risk of intra- or postoperative hemodynamic depression in CAS and might increase the risk of major adverse cardiovascular events. Given the added complications and the lack of evidence supporting long term patency, PSB should be only selectively used.
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Angioplastia com Balão/instrumentação , Angioplastia com Balão/métodos , Estenose das Carótidas/terapia , Hemodinâmica , Stents , Idoso , Angioplastia com Balão/efeitos adversos , Pressão Arterial , Baltimore , Bradicardia/etiologia , Bradicardia/fisiopatologia , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/fisiopatologia , Feminino , Frequência Cardíaca , Humanos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Modelos Logísticos , Masculino , Razão de Chances , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Resultado do TratamentoRESUMO
This study uses a nationally representative data sample to assess the effect of maternal height as an intergenerational influence on under-five mortality. Data from the 2003 and 2008 Nigerian Demographic Health Survey (NDHS) (n = 41,005) selecting women aged 15 to 49 yrs whose most recent births were within 5 years (n = 23,568), were analyzed. The outcome measure was under-five mortality. Independent variables included maternal height categorized as > or = 63 inch, 61-62.9 inch, 59.1-60.9 inch, < 59.1 inch. Confounding factors were controlled for. A multivariable logistic regression was used to obtain odds ratio estimates along with their respective confidence interval. After adjusting for confounding factors, we found that each 1 inch increase in maternal height, was associated with a decreased odds of mortality OR 0.98 (95% CI 0.97-0.99). The OR of under-five mortality when comparing women > or = 63 inch versus women < 59.1 inch was 1.13 (95% CI 0.98-1.31). The population attributable fraction of child death due to maternal short stature was 0.36.
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Estatura , Mortalidade da Criança , Mães , Adolescente , Adulto , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Gravidez , Fatores de RiscoRESUMO
OBJECTIVE: Antiretroviral therapy (ART) containing integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain. Yet few studies have delineated between exposure to "anchor" drugs (protease inhibitors [PI], non-nucleoside reverse transcriptase inhibitors [NNRTI] or INSTIs) and exposure to nucleoside reverse transcriptase inhibitors (NRTIs). DESIGN: In this cohort of antiretroviral (ARV) naïve patients who initiated ART from 2008-2022, we analyzed body mass index (BMI) gain for 8 contemporary "anchor" drugs and 3 contemporary NRTIs during the first 3âyears of ART. We censored patients if they stopped, switched, or added another ARV to their regimen. METHODS: We used generalized estimating equations (GEE) to assess the association between BMI gain and choice of ART and a non-linear mixed model for the marginal coefficients of determination. We adjusted for time, baseline demographic and HIV-characteristics, and time-updated HIV and substance use related variables. RESULTS: 4,194 patients contributed 20,528 BMI measurements which were used for multivariable modeling. Most patients were black (55%) and male (77%). Median BMI gain over 3âyears was +1.9âkg/m2 (IQR 0.1-4.1). ARV use accounted for only 9% of the predicted BMI change. Only efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) were independently associated with (lower) weight gain while no differences between INSTIs, PIs, or rilpivirine were observed, nor between TAF and abacavir. CONCLUSIONS: The choice of initial ART had little impact on weight gain. INSTIs or TAF were not independently associated with weight change after ART initiation, but EFV and TDF were.
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BACKGROUND: Several studies have described the burden of trauma care, but few have explored the economic burden of trauma inpatient costs from a payer's perspective or highlighted the differences in the average costs per person by payer status. The present study provides a conservative inpatient national trauma cost estimate and describes the variation in average inpatient trauma cost by payer status. METHODS: A retrospective analysis of patients who had received trauma care at hospitals in the Nationwide Inpatient Sample from 2005-2010 was conducted. Our sample patients were selected using the appropriate "International Classification of Diseases, Ninth Revision, Clinical Modification" codes to identify admissions due to traumatic injury. The data were weighted to provide national population estimates, and all cost and charges were converted to 2010 US dollar equivalents. Generalized linear models were used to describe the costs by payer status, adjusting for patient characteristics, such as age, gender, and race, and hospital characteristics, such as location, teaching status, and patient case mix. RESULTS: A total of 2,542,551 patients were eligible for the present study, with the payer status as follows: 672,960 patients (26.47%) with private insurance, 1,244,817 (48.96%) with Medicare, 262,256 (10.31%) with Medicaid, 195,056 (7.67%) with self-pay, 18,506 (0.73%) with no charge, and 150,956 (5.94%) with other types of insurance. The estimated yearly trauma inpatient cost burden was highest for Medicare at $17,551,393,082 (46.79%), followed by private insurance ($10,772,025,421 [28.72%]), Medicaid ($3,711,686,012 [9.89%], self-pay ($2,831,438,460 [7.55%]), and other payer types ($2,370,187,494 [6.32%]. The estimated yearly trauma inpatient cost burden was $274,598,190 (0.73%) for patients who were not charged for their inpatient trauma treatment. Our adjusted national inpatient trauma yearly costs were estimated at $37,511,328,659 US dollars. Privately insured patients had a significantly higher mean cost per person than did the Medicare, Medicaid, self-pay, or no charge patients. CONCLUSIONS: The results of the present study have demonstrated that the distribution of trauma burden across payers is significantly different from that of the overall healthcare system and suggest that although the burden of trauma is high, the burden of self-pay or nonreimbursed inpatient services is actually lower than that of overall medical care.
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Custos de Cuidados de Saúde/estatística & dados numéricos , Seguro Saúde/economia , Medicaid/economia , Medicare/economia , Ferimentos não Penetrantes/economia , Ferimentos Penetrantes/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Classificação Internacional de Doenças/economia , Tempo de Internação/economia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Ferimentos não Penetrantes/epidemiologia , Ferimentos Penetrantes/epidemiologia , Adulto JovemRESUMO
Eosinophilic gastrointestinal diseases are rare disorders characterized by infiltration of eosinophils in one or multiple segments of the gastrointestinal tract. Hypersensitivity to food or environmental allergens is believed to play an important role in the pathogenesis. In this case report, we describe a 61-year-old man who developed eosinophilic gastroenteritis and colitis with severe peripheral eosinophilia after intragastric balloon (IGB) placement for weight loss. His symptoms and peripheral eosinophilia improved rapidly after removal of the IGB without the need for immunomodulatory therapies or diet modifications. This case suggests a possible association between IGB and eosinophilic gastrointestinal diseases, which warrants clinicians' awareness and further studies.
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BACKGROUND: Protein-energy malnutrition (PEM) diminishes amino acid and energy availability, impairing the body's healing capability after injury, such as in myocardial damage following acute myocardial infarction (AMI). AIMS: We sought to investigate the influence of PEM on clinical outcomes of AMI. METHODS: We identified records with a primary discharge diagnosis of AMI from the Nationwide Inpatient Sample (2012-2014), stratified by concomitant PEM. We matched PEM to no-PEM (1:1) using a greedy algorithm-based propensity methodology and estimated the impact of PEM on health outcomes (SAS 9.4). RESULTS: Of the 332,644 hospitalizations for AMI, 11,675 had concomitant PEM accounting for roughly $US 1.5 billion and over 119,792 hospital days. PEM was associated with older age (74.43- vs. 66.90-years; P < 0.0001), female sex (49.19% vs. 38.44%; P < 0.0001), black race (12.78% vs. 10.46%; P < 0.0001), and higher comorbidity burden (Deyo > 3: 32.77% vs. 16.69%; P < 0.0001). After propensity matching, PEM was associated with higher mortality (Adjusted odds ratio [AOR]: 1.59 [1.46-1.73]), cardiogenic shock (AOR: 2.26 [2.08-2.44]), discharge to secondary facilities (AOR: 2.21 [2.10-2.33]), charges ($135,500 [$131,956-139,139] vs. $81,084 [$79,241-82,970]), cardiac artery bypass surgery (AOR:1.81 [1.66-1.97]), intra-aortic balloon pump placement (AOR: 1.83 [1.65-2.04]) and longer length of stay (10.15- vs. 5.52-days). CONCLUSIONS: PEM is a predisposing factor for devastating clinical outcomes among AMI hospitalizations. Higher prevention, identification and management of PEM among high-risk individuals (older age, female sex, and black race) residing in the community are needed.