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BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.
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Neoplasias Colorretais , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Mutação , Neoplasias Peritoneais , Proteínas Proto-Oncogênicas p21(ras) , Proteína Supressora de Tumor p53 , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Feminino , Masculino , Estudos Retrospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/genética , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/genética , Prognóstico , Taxa de Sobrevida , Terapia Combinada , Seguimentos , Idoso , Biomarcadores Tumorais/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , AdultoRESUMO
Heme b (iron protoporphyrin IX) is an essential but potentially cytotoxic cofactor, signaling molecule, and nutritional source of iron. Its importance in cell biology and metabolism is underscored by the fact that numerous diseases, including various cancers, neurodegenerative disorders, infectious diseases, anemias, and porphyrias, are associated with the dysregulation of heme synthesis, degradation, trafficking, and/or transport. Consequently, methods to measure, image, and quantify heme in cells are required to better understand the physiology and pathophysiology of heme. Herein, we describe fluorescence-based protocols to probe heme bioavailability and trafficking dynamics using genetically encoded fluorescent heme sensors in combination with various modalities, such as confocal microscopy, flow cytometry, and microplate readers. Additionally, we describe a protocol for measuring total heme and its precursor protoporphyrin IX using a fluorometric assay that exploits porphyrin fluorescence. Together, the methods described enable the monitoring of total and bioavailable heme to study heme homeostatic mechanisms in virtually any cell type and organism.
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Fluorometria , Heme , Heme/metabolismo , Fluorometria/métodos , Humanos , Protoporfirinas/metabolismo , Citometria de Fluxo/métodos , Microscopia Confocal/métodos , Disponibilidade Biológica , AnimaisRESUMO
OBJECTIVES: Timely control of hypertension is vital to prevent comorbidities. We evaluated the association of race/ethnicity and HIV infection with incident hypertension outcomes, including awareness, treatment, and control. DESIGN: We evaluated cisgender women living with HIV and sociodemographically matched women living without HIV recruited into four Southern sites of the Women's Interagency HIV Study (WIHS) (2013-2019). METHODS: We calculated measurements of the time to four events or censoring: incident hypertension, hypertension awareness, hypertension treatment, and hypertension control. Hazard ratios for race/ethnicity and HIV status were calculated for each outcome using Cox proportional-hazards models adjusted for sociodemographic, behavioral, and clinical risk factors. RESULTS: Among 712 women, 56% were hypertensive at baseline. Forty-five percentage of the remaining women who were normotensive at baseline developed incident hypertension during follow-up. Non-Hispanic white and Hispanic women had faster time to hypertension control compared with non-Hispanic black women ( P â=â0.01). In fully adjusted models, women living with HIV who were normotensive at baseline had faster time to treatment compared with normotensive women living without HIV ( P â=â0.04). CONCLUSION: In our study of women in the US South, non-Hispanic black women became aware of their hypertension diagnosis more quickly than non-Hispanic white and Hispanic women but were slower to control their hypertension. Additionally, women living with HIV more quickly treated and controlled their hypertension compared with women living without HIV.
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Infecções por HIV , Hipertensão , Humanos , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Adulto , Pessoa de Meia-Idade , Conhecimentos, Atitudes e Prática em Saúde , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: Estrogens may protect the gut barrier and reduce microbial translocation and immune activation, which are prevalent in HIV infection. We investigated relationships of the menopausal transition and estrogens with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV. DESIGN: Longitudinal and cross-sectional studies nested in the Women's Interagency HIV Study. METHODS: Intestinal fatty acid binding protein, lipopolysaccharide binding protein, and soluble CD14 (sCD14) levels were measured in serum from 77 women (43 with HIV) before, during, and after the menopausal transition (â¼6 measures per woman over â¼13 years). A separate cross-sectional analysis was conducted among 72 postmenopausal women with HIV with these biomarkers and serum estrogens. RESULTS: Women in the longitudinal analysis were a median age of 43 years at baseline. In piecewise, linear, mixed-effects models with cutpoints 2 years before and after the final menstrual period to delineate the menopausal transition, sCD14 levels increased over time during the menopausal transition (Beta [95% CI]: 38 [12 to 64] ng/mL/yr, P = 0.004), followed by a decrease posttransition (-46 [-75 to -18], P = 0.001), with the piecewise model providing a better fit than a linear model (P = 0.0006). In stratified analyses, these results were only apparent in women with HIV. In cross-sectional analyses, among women with HIV, free estradiol inversely correlated with sCD14 levels (r = -0.26, P = 0.03). Lipopolysaccharide binding protein and intestinal fatty acid binding protein levels did not appear related to the menopausal transition and estrogen levels. CONCLUSIONS: Women with HIV may experience heightened innate immune activation during menopause, possibly related to the depletion of estrogens.
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Translocação Bacteriana , Biomarcadores , Estrogênios , Proteínas de Ligação a Ácido Graxo , Infecções por HIV , Receptores de Lipopolissacarídeos , Menopausa , Humanos , Feminino , Infecções por HIV/imunologia , Infecções por HIV/sangue , Adulto , Estudos Transversais , Receptores de Lipopolissacarídeos/sangue , Menopausa/sangue , Biomarcadores/sangue , Pessoa de Meia-Idade , Estudos Longitudinais , Estrogênios/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Glicoproteínas de Membrana/sangue , Proteínas de Fase Aguda , Proteínas de TransporteRESUMO
People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.
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Senilidade Prematura , Infecções por HIV , Masculino , Humanos , Feminino , Imunoglobulina G , Estudos Transversais , Envelhecimento , Inflamação/complicações , PolissacarídeosRESUMO
BACKGROUND: Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. METHODS: We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women's Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria-diabetes associations are explained by altered metabolites and proteins. RESULTS: Seven gut bacterial genera were identified to be associated with diabetes (FDR-q < 0.1), with positive associations for Shigella, Escherichia, Megasphaera, and Lactobacillus, and inverse associations for Adlercreutzia, Ruminococcus, and Intestinibacter. Importantly, the associations of most species, especially Adlercreutzia and Ruminococcus, were largely independent of antidiabetic medications use. Meanwhile, 18 proteins and 76 metabolites, including 3 microbially derived metabolites (trimethylamine N-oxide, phenylacetylglutamine (PAGln), imidazolepropionic acid (IMP)), 50 lipids (e.g., diradylglycerols (DGs) and triradylglycerols (TGs)) and 23 non-lipid metabolites, were associated with diabetes (FDR-q < 0.1), with the majority showing positive associations and more than half of them (59/76) associated with incident diabetes. In mediation analyses, several proteins, especially interleukin-18 receptor 1 and osteoprotegerin, IMP and PAGln partially mediate the observed bacterial genera-diabetes associations, particularly for those of Adlercreutzia and Escherichia. Many diabetes-associated metabolites and proteins were altered in HIV, but no effect modification on their associations with diabetes was observed by HIV. CONCLUSION: Among individuals with and without HIV, multiple gut bacterial genera, blood metabolites, and proinflammatory proteins were associated with diabetes. The observed mediated effects by metabolites and proteins in genera-diabetes associations highlighted the potential involvement of inflammatory and metabolic perturbations in the link between gut dysbiosis and diabetes in the context of HIV infection.
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Diabetes Mellitus , Infecções por HIV , Masculino , Humanos , Feminino , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , Estudos de Coortes , Disbiose/complicações , Estudos Transversais , BactériasRESUMO
Ubiquinol or coenzyme Q (CoQ) is a lipid-soluble electron carrier in the respiratory chain and an electron acceptor for various enzymes in metabolic pathways that intersect at this cofactor hub in the mitochondrial inner membrane. The reduced form of CoQ is an antioxidant, which protects against lipid peroxidation. In this study, we have optimized a UV-detected HPLC method for CoQ analysis from biological materials, which involves a rapid single-step extraction into n-propanol followed by direct sample injection onto a column. Using this method, we have measured the oxidized, reduced, and total CoQ pools and monitored shifts in the CoQ redox status in response to cell culture conditions and bioenergetic perturbations. We find that hypoxia or sulfide exposure induces a reductive shift in the intracellular CoQ pool. The effect of hypoxia is, however, rapidly reversed by exposure to ambient air. Interventions at different loci in the electron transport chain can induce sizeable redox shifts in the oxidative or reductive direction, depending on whether they are up- or downstream of complex III. We have also used this method to confirm that CoQ levels are higher and more reduced in murine heart versus brain. In summary, the availability of a convenient HPLC-based method described herein will facilitate studies on CoQ redox dynamics in response to environmental, nutritional, and endogenous alterations.
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Oxirredução , Ubiquinona , Animais , Humanos , Camundongos , Cromatografia Líquida de Alta Pressão/métodos , Ubiquinona/química , Ubiquinona/metabolismo , Miocárdio/enzimologia , Encéfalo/enzimologia , Feminino , Camundongos Endogâmicos C57BL , Células HT29RESUMO
BACKGROUND: While cholecystectomy is one of the most common operations performed in the United States, there is a continued debate regarding its prophylactic role in elective surgery. Particularly among patients with peritoneal carcinomatosis who undergo cytoreduction surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), further abdominal operations may pose increasing morbidity due to intraabdominal adhesions and potential recurrence. This bi-institutional retrospective study aims to assess postoperative morbidity associated with prophylactic cholecystectomy at the time of CRS-HIPEC. METHODS: We performed a bi-institutional retrospective analysis of 578 patients who underwent CRS-HIPEC from 2011 to 2021. Postoperative outcomes among patients who underwent prophylactic cholecystectomy at the time of CRS-HIPEC were compared to patients who did not, particularly rate of bile leak, hospital length of stay, rate of Clavien-Dindo classification morbidity grade III or greater, and number of hospital re-admissions within 30 days. RESULTS: Of the 535 patients available for analysis, 206 patients (38.3%) underwent a prophylactic cholecystectomy. Of the 3 bile leaks (1.5%) that occurred among patients who underwent prophylactic cholecystectomy, all 3 occurred in patients who underwent a concomitant liver resection. There were no significant differences in hospital length of stay, postoperative morbidity, and number of hospital re-admissions among patients who underwent prophylactic cholecystectomy compared to those who did not. CONCLUSION: Prophylactic cholecystectomy in patients undergoing CRS-HIPEC is not associated with increased morbidity or increased bile leak risk compared to historical data. While the benefits of prophylactic cholecystectomy are not yet elucidated, it may be considered to avoid potential future morbid operations for biliary disease.
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Colecistectomia , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Estudos Retrospectivos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Peritoneais/terapia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Adulto , Tempo de Internação/estatística & dados numéricos , Idoso , Terapia CombinadaRESUMO
Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism in mammals. At a cellular level, H2S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, the durability of these changes is unknown. We report that despite its volatility, H2S preconditioning increases P50(O2), the O2 pressure for half-maximal cellular respiration, and has pleiotropic effects on oxidative metabolism that persist up to 24 to 48 h later. Notably, cyanide, another complex IV inhibitor, does not induce this type of metabolic memory. Sulfide-mediated prolonged fractional inhibition of complex IV by H2S is modulated by sulfide quinone oxidoreductase, which commits sulfide to oxidative catabolism. Since induced hypometabolism can be beneficial in disease settings that involve insufficient or interrupted blood flow, our study has important implications for attenuating reperfusion-induced ischemic injury and/or prolonging the shelf life of biologics like platelets.
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Sulfeto de Hidrogênio , Traumatismo por Reperfusão , Animais , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Sulfetos , Oxirredução , Mamíferos/metabolismoRESUMO
BACKGROUND: Social unacceptability of food access is part of the lived experience of food insecurity but is not assessed as part of the United States Household Food Security Survey Module (HFSSM). OBJECTIVES: The objectives were as follows: 1) to determine the psychometric properties of 2 additional items on social unacceptability in relation to the HFSSM items and 2) to test whether these 2 items provided added predictive accuracy to that of the HFSSM items for mental health outcomes. METHODS: Cross-sectional data used were from the Intersection of Material-Need Insecurities and HIV and Cardiovascular Health substudy of the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study. Data on the 10-item HFSSM and 2 new items reflecting social unacceptability were collected between Fall 2020 and Fall 2021 from 1342 participants from 10 United States cities. The 2 social unacceptability items were examined psychometrically in relation to the HFSSM-10 items using models from item response theory. Linear and logistic regression was used to examine prediction of mental health measured by the 20-item Center for Epidemiologic Studies Depression scale and the 10-item Perceived Stress Scale. RESULTS: The social unacceptability items were affirmed throughout the range of severity of food insecurity but with increasing frequency at higher severity of food insecurity. From item response theory models, the subconstructs reflected in the HFSSM-10 and the subconstruct of social unacceptability were distinct, not falling into one dimension. Regression models confirmed that social unacceptability was distinct from the subconstructs reflected in the HFSSM-10. The social unacceptability items as a separate scale explained more (â¼1%) variation in mental health than when combined with the HFSSM-10 items in a single scale, and the social unacceptability subconstruct explained more (â¼1%) variation in mental health not explained by the HFSSM-10. CONCLUSIONS: Two social unacceptability items used as a separate scale along with the HFSSM-10 predicted mental health more accurately than did the HFSSM-10 alone.
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Abastecimento de Alimentos , Infecções por HIV , Testes Psicológicos , Autorrelato , Humanos , Feminino , Estados Unidos , Estudos de Coortes , Estudos Transversais , Segurança AlimentarRESUMO
OBJECTIVE: To develop a severity-adjusted, hospital-level benchmarking comparative performance report for postoperative organ space infection and antibiotic utilization in children with complicated appendicitis. BACKGROUND: No benchmarking data exist to aid hospitals in identifying and prioritizing opportunities for infection prevention or antimicrobial stewardship in children with complicated appendicitis. METHODS: This was a multicenter cohort study using NSQIP-Pediatric data from 16 hospitals participating in a regional research consortium, augmented with antibiotic utilization data obtained through supplemental chart review. Children with complicated appendicitis who underwent appendectomy from 07/01/2015 to 06/30/2020 were included. Thirty-day postoperative OSI rates and cumulative antibiotic utilization were compared between hospitals using observed-to-expected (O/E) ratios after adjusting for disease severity using mixed effects models. Hospitals were considered outliers if the 95% confidence interval for O/E ratios did not include 1.0. RESULTS: 1790 patients were included. Overall, the OSI rate was 15.6% (hospital range: 2.6-39.4%) and median cumulative antibiotic utilization was 9.0 days (range: 3.0-13.0). Across hospitals, adjusted O/E ratios ranged 5.7-fold for OSI (0.49-2.80, P=0.03) and 2.4-fold for antibiotic utilization (0.59-1.45, P<0.01). Three (19%) hospitals were outliers for OSI (1 high and 2 low performers), and eight (50%) were outliers for antibiotic utilization (5 high and 3 low utilizers). Ten (63%) hospitals were identified as outliers in one or both measures. CONCLUSIONS: A comparative performance benchmarking report may help hospitals identify and prioritize quality improvement opportunities for infection prevention and antimicrobial stewardship, as well as identify exemplar performers for dissemination of best practices.
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BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.
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Doenças das Artérias Carótidas , Estenose das Carótidas , Coinfecção , Infecções por HIV , Hepatite C , Placa Aterosclerótica , Adulto , Feminino , Humanos , Masculino , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Estenose das Carótidas/complicações , Estudos de Coortes , Coinfecção/diagnóstico por imagem , Coinfecção/epidemiologia , Coinfecção/complicações , Estudos Transversais , Hepacivirus , Hepatite C/complicações , Hepatite C/diagnóstico por imagem , Hepatite C/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/epidemiologia , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/complicações , Fatores de Risco , Pessoa de Meia-Idade , Estudos Multicêntricos como AssuntoRESUMO
Inter-organellar communication is critical for cellular metabolic homeostasis. One of the most abundant inter-organellar interactions are those at the endoplasmic reticulum and mitochondria contact sites (ERMCS). However, a detailed understanding of the mechanisms governing ERMCS regulation and their roles in cellular metabolism are limited by a lack of tools that permit temporal induction and reversal. Through unbiased screening approaches, we identified fedratinib, an FDA-approved drug, that dramatically increases ERMCS abundance by inhibiting the epigenetic modifier BRD4. Fedratinib rapidly and reversibly modulates mitochondrial and ER morphology and alters metabolic homeostasis. Moreover, ERMCS modulation depends on mitochondria electron transport chain complex III function. Comparison of fedratinib activity to other reported inducers of ERMCS revealed common mechanisms of induction and function, providing clarity and union to a growing body of experimental observations. In total, our results uncovered a novel epigenetic signaling pathway and an endogenous metabolic regulator that connects ERMCS and cellular metabolism.
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Importance: Gangrenous, suppurative, and exudative (GSE) findings have been associated with increased surgical site infection (SSI) risk and resource use in children with nonperforated appendicitis. Establishing the role for postoperative antibiotics may have important implications for infection prevention and antimicrobial stewardship. Objective: To compare SSI rates in children with nonperforated appendicitis with GSE findings who did and did not receive postoperative antibiotics. Design, Setting, and Participants: This was a retrospective cohort study using American College of Surgeons' National Surgical Quality Improvement Program (NSQIP)-Pediatric Appendectomy Targeted data from 16 hospitals participating in a regional research consortium. NSQIP data were augmented with operative report and antibiotic use data obtained through supplemental medical record review. Children with nonperforated appendicitis with GSE findings who underwent appendectomy between July 1, 2015, and June 30, 2020, were identified using previously validated intraoperative criteria. Data were analyzed from October 2022 to July 2023. Exposure: Continuation of antibiotics after appendectomy. Main Outcomes and Measures: Rate of 30-day postoperative SSI including both incisional and organ space infections. Complementary hospital and patient-level analyses were conducted to explore the association between postoperative antibiotic use and severity-adjusted outcomes. The hospital-level analysis explored the correlation between postoperative antibiotic use and observed to expected (O/E) SSI rate ratios after adjusting for differences in disease severity (presence of gangrene and postoperative length of stay) among hospital populations. In the patient-level analysis, propensity score matching was used to balance groups on disease severity, and outcomes were compared using mixed-effects logistic regression to adjust for hospital-level clustering. Results: A total of 958 children (mean [SD] age, 10.7 [3.7] years; 567 male [59.2%]) were included in the hospital-level analysis, of which 573 (59.8%) received postoperative antibiotics. No correlation was found between hospital-level SSI O/E ratios and postoperative antibiotic use when analyzed by either overall rate of use (hospital median, 53.6%; range, 31.6%-100%; Spearman ρ = -0.10; P = .71) or by postoperative antibiotic duration (hospital median, 1 day; range, 0-7 days; Spearman ρ = -0.07; P = .79). In the propensity-matched patient-level analysis including 404 patients, children who received postoperative antibiotics had similar rates of SSI compared with children who did not receive postoperative antibiotics (3 of 202 [1.5%] vs 4 of 202 [2.0%]; odds ratio, 0.75; 95% CI, 0.16-3.39; P = .70). Conclusions and Relevance: Use of postoperative antibiotics did not improve outcomes in children with nonperforated appendicitis with gangrenous, suppurative, or exudative findings.
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Antibacterianos , Apendicectomia , Apendicite , Gangrena , Infecção da Ferida Cirúrgica , Adolescente , Criança , Feminino , Humanos , Masculino , Antibacterianos/uso terapêutico , Apendicite/cirurgia , Cuidados Pós-Operatórios , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
Background: Hypertension-related diseases are major causes of morbidity among women living with HIV. We evaluated cross-sectional associations of race/ethnicity and HIV infection with hypertension prevalence, awareness, treatment, and control. Methods: Among women recruited into Southern sites of the Women's Interagency HIV Study (2013-2015), hypertension was defined as (1) systolic blood pressure ≥140â mm Hg or diastolic blood pressure ≥90â mm Hg according to clinical guidelines when data were collected, (2) self-report of hypertension, or (3) use of antihypertensive medication. Awareness was defined as self-report of hypertension, and treatment was self-report of any antihypertensive medication use. Blood pressure control was defined as <140/90â mm Hg at baseline. Prevalence ratios for each hypertension outcome were estimated through Poisson regression models with robust variance estimators adjusted for sociodemographic, behavioral, and clinical risk factors. Results: Among 712 women, 56% had hypertension and 83% were aware of their diagnosis. Of those aware, 83% were using antihypertensive medication, and 63% of those treated had controlled hypertension. In adjusted analyses, non-Hispanic White and Hispanic women had 31% and 48% lower prevalence of hypertension than non-Hispanic Black women, respectively. Women living with HIV who had hypertension were 19% (P = .04) more likely to be taking antihypertension medication when compared with women living without HIV. Conclusions: In this study population of women living with and without HIV in the US South, the prevalence of hypertension was lowest among Hispanic women and highest among non-Hispanic Black women. Despite similar hypertension prevalence, women living with HIV were more likely to be taking antihypertensive medication when compared with women living without HIV.
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BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tube placement is the most common enteral access for long-term feeding. The aim of our study is to assess the feasibility and safety of immediate PEG tube use after initial placement. METHODS: We conducted a single-center retrospective cohort study between August 2006 and August 2016. Prior to August 2011, tube feedings were delayed for ≥4 h after initial PEG placement, compared with immediate use (<1 h) after August 2011. Primary outcomes were complication rates within 30 days of placement. Secondary outcomes were impact of morbidity, mortality, length of stay, and need for repeat PEG placement. RESULTS: Our study included 1296 patients during the 10-year period, of which 704 underwent delayed use and 592 underwent immediate use (744 inpatient and 552 outpatient). There were no significant differences between the delayed-use and immediate-use PEG with regard to complications (3.4% vs 4.4%; P = 0.76). Subgroup analysis also reflected no significant differences in complications between inpatient and outpatient groups. For inpatients, there were no substantial differences in inpatient mortality (3.9% vs 3.3%; P = 0.70), mortality within 30 days of discharge (13.8% vs 13.1%; P = 0.15), readmissions (38.2% vs 34.3%; P = 0.23), repeat PEG placement (0.7% vs 1.5%; P = 0.46), and length of stay (13.3 vs 13.9 days; P = 0.99). CONCLUSION: Patients who received immediate enteral nutrition after PEG tube placement did not have any increased complications, morbidity, or mortality; and it is just as safe when compared with patients who received delayed feeding.