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1.
J Infect Dis ; 229(3): 625-629, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38309710

RESUMO

Infectious diseases (ID) research is vital for global public health, typically led by physician-scientists. This Perspective addresses challenges in the ID workforce and suggests solutions. Physician-scientists have made key discoveries that have significantly impacted human health. The importance of ID research in understanding diseases, leading to treatments and vaccines, is emphasized, along with the need to address persistent and new infections, antimicrobial resistance, and threats like HIV and influenza. The paper analyzes the physician-scientist workforce's struggles, including funding, training, and research-practice integration gaps. We suggest increased funding, better training, and mentorship, more collaborative and interdisciplinary research, and improved recognition systems. The article stresses the urgency of supporting physician-scientists in ID, advocating for proactive prevention and preparedness, and calls for immediate action to enhance ID research and care.


Assuntos
Pesquisa Biomédica , Doenças Transmissíveis , Educação Médica , Médicos , Humanos , Pesquisa Biomédica/tendências , Recursos Humanos , Educação Médica/tendências
2.
Cancer ; 129(13): 1986-1994, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36943918

RESUMO

BACKGROUND: The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long-term survival are not well described. METHODS: In this cross-sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long-term survival (n = 16). LTS was defined as >4 years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls. RESULTS: All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6 years (4-14 years) for LTSs without evidence of disease compared to a median disease-free survival of 1.8 years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia muciniphila species. CONCLUSIONS: Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia muciniphila. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa. PLAIN LANGUAGE SUMMARY: Although pancreatic cancer treatments have improved, the number of long-term survivors has remained stagnant with a 5-year overall survival estimate of 9%. Emerging evidence suggests that microbes within the gastrointestinal tract can influence cancer response through activation of the immune system. In this study, we profiled the stool microbiome in long-term survivors of pancreas cancer and controls. Several enriched species previously associated with enhanced tumor immune response were observed including Faecalibacterium prausnitzii and Akkermansia muciniphila. These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.


Assuntos
Metagenoma , Neoplasias Pancreáticas , Humanos , Estudos Transversais , Verrucomicrobia , Fezes , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Sobreviventes
3.
Transpl Infect Dis ; 25(6): e14179, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37910558

RESUMO

BACKGROUND: Viral infections such as adenovirus (ADV), BK virus (BKV), and cytomegalovirus (CMV) after kidney transplantation negatively impact outcomes in transplant recipients despite advancements in screening and antiviral therapy. We describe our experience of using the virus-specific T cell therapy (VSTs) in kidney transplant recipients (KTR) at our transplant center. METHODS: This is a retrospective, single center review of KTR with ADV, BKV and CMV infections between June 2021 and December 2022. These patients received third party VSTs as part of the management of infections. The immunosuppression, details of infection and outcome data were obtained from electronic medical records. RESULTS: Two cases of ADV infection resolved after one infusion of VSTs. The response rate of BKV and CMV infection was not as robust with close to 50% reduction in median viral load after VSTs. Out of 23 patients, two patients developed chronic allograft nephropathy from membranoproliferative glomerulonephritis and acute rejection. CONCLUSION: Patients that are resistant to antivirals or who have worsening viremia despite conventional management may benefit from VSTs therapy to treat underlying viral infection. Additional studies are needed to ascertain efficacy and short- and long-term risks secondary to VSTs.


Assuntos
Vírus BK , Infecções por Citomegalovirus , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Transplantados , Infecções por Polyomavirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/complicações , Terapia Baseada em Transplante de Células e Tecidos , Vírus BK/fisiologia
4.
Respirology ; 26(12): 1181-1187, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34459069

RESUMO

BACKGROUND AND OBJECTIVE: Ecological studies have suggested an association between exposure to particulate matter ≤2.5 µm (PM2.5 ) and coronavirus disease 2019 (COVID-19) severity. However, these findings are yet to be validated in individual-level studies. We aimed to determine the association of long-term PM2.5 exposure with hospitalization among individual patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We estimated the 10-year (2009-2018) PM2.5 exposure at the residential zip code of COVID-19 patients diagnosed at the University of Cincinnati healthcare system between 13 March 2020 and 30 September 2020. Logistic regression was used to determine the odds ratio (OR) and 95% CI for COVID-19 hospitalizations associated with PM2.5 , adjusting for socioeconomic characteristics and comorbidities. RESULTS: Among the 14,783 COVID-19 patients included in our study, 13.6% were hospitalized; the geometric mean (SD) PM2.5 was 10.48 (1.12) µg/m3 . In adjusted analysis, 1 µg/m3 increase in 10-year annual average PM2.5 was associated with 18% higher hospitalization (OR: 1.18, 95% CI: 1.11-1.26). Likewise, 1 µg/m3 increase in PM2.5 estimated for the year 2018 was associated with 14% higher hospitalization (OR: 1.14, 95% CI: 1.08-1.21). CONCLUSION: Long-term PM2.5 exposure is associated with increased hospitalization in COVID-19. Therefore, more stringent COVID-19 prevention measures may be needed in areas with higher PM2.5 exposure to reduce the disease morbidity and healthcare burden.


Assuntos
Poluentes Atmosféricos , Poluição do Ar/efeitos adversos , COVID-19/epidemiologia , Exposição Ambiental/efeitos adversos , Hospitalização/estatística & dados numéricos , Material Particulado/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , COVID-19/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Material Particulado/análise , SARS-CoV-2 , Índice de Gravidade de Doença
6.
Hepatology ; 67(5): 1673-1682, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29205441

RESUMO

Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. CONCLUSION: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).


Assuntos
Hepacivirus , Hepatite C/transmissão , Transplante de Fígado/efeitos adversos , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Seguimentos , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Incidência , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Reação em Cadeia da Polimerase , Estudos Prospectivos , Taxa de Sobrevida , Doadores de Tecidos/estatística & dados numéricos , Adulto Jovem
7.
Clin Infect Dis ; 66(11): 1678-1686, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29438475

RESUMO

Background: Blood cultures are approximately 50% sensitive for diagnosing invasive candidiasis. The T2Candida nanodiagnostic panel uses T2 magnetic resonance and a dedicated instrument to detect Candida directly within whole blood samples. Methods: Patients with Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, or Candida krusei candidemia were identified at 14 centers using diagnostic blood cultures (dBCs). Follow-up blood samples were collected concurrently for testing by T2Candida and companion cultures (cBCs). T2Candida results are reported qualitatively for C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis. T2Candida and cBCs were positive if they detected a species present in the dBC. Results: Median time between collection of dBC and T2Candida/cBC samples in 152 patients was 55.5 hours (range, 16.4-148.4). T2Candida and cBCs were positive in 45% (69/152) and 24% (36/152) of patients, respectively (P < .0001). T2Candida clinical sensitivity was 89%, as positive results were obtained in 32/36 patients with positive cBCs. Combined test results were both positive (T2+/cBC+), 21% (32/152); T2+/cBC-, 24% (37/152); T2-/cBC+, 3% (4/152); and T2-/cBC-, 52% (79/152). Prior antifungal therapy, neutropenia, and C. albicans candidemia were independently associated with T2Candida positivity and T2+/cBC- results (P values < .05). Conclusions: T2Candida was sensitive for diagnosing candidemia at the time of positive blood cultures. In patients receiving antifungal therapy, T2Candida identified bloodstream infections that were missed by cBCs. T2Candida may improve care by shortening times to Candida detection and species identification compared to blood cultures, retaining sensitivity during antifungal therapy and rendering active candidemia unlikely if results are negative. Clinical Trials Registration: NCT01525095.


Assuntos
Candida/isolamento & purificação , Candidemia/sangue , Candidemia/diagnóstico , Espectroscopia de Ressonância Magnética/métodos , Testes Sorológicos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
8.
Support Care Cancer ; 26(9): 3127-3134, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29594489

RESUMO

BACKGROUND: Clostridium difficile infection (CDI) is the most common hospital-acquired infection. Unfortunately, genes that identify CDI-susceptible patients have not been well described. We performed a genome-wide association study (GWAS) to determine genetic variants associated with the development of CDI. METHODS: A cohort study of Caucasian patients undergoing autologous stem cell transplantation for multiple myeloma was performed. Patients were genotyped using Illumina® Whole Genome Genotyping Infinium chemistry. We then compared CDI-positive to CDI-negative patients using logistic regression for baseline clinical factors and false discovery rate (FDR) for genetic factors [single nucleotide polymorphisms (SNPs)]. SNPs associated with CDI at FDR of p < 0.01 were then incorporated into a logistic regression model combining clinical and genetic factors. RESULTS: Of the 646 patients analyzed (59.7% male), 57 patients were tested CDI positive (cases) and were compared to 589 patients who were tested negative (controls). Hemoglobin, albumin, and hematocrit were lower for cases (p < 0.05). Eight SNPs on five genes (FLJ16171, GORASP2, RLBP1L1, ASPH, ATP7B) were associated with CDI at FDR p < 0.01. In the combined clinical and genetic model, low albumin and three genes RLBP1L1, ASPH, and ATP7B were associated with CDI. CONCLUSION: Low serum albumin and genes RLBP1L1 and ASPH located on chromosome 8 and ATP7B on chromosome 13 were associated with CDI. Of particular interest is ATP7B given its copper modulatory role and the sporicidal properties of copper against Clostridium difficile.


Assuntos
Infecções por Clostridium/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Infecções por Clostridium/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Anaerobe ; 45: 101-105, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28223256

RESUMO

Clostridium difficile is the leading cause of healthcare-associated infections in the United States. Clinically, C. difficile-associated disease can present as asymptomatic colonization, self-limited diarrheal illness or severe colitis (that may result in death). This variability in disease course and outcomes suggests that host factors play an important role as key determinants of disease severity. Currently, there are several scoring indices to estimate severity of C. difficile-associated disease. Leukocytosis and renal failure are considered to be the most important predictors of C. difficile disease severity in hosts with a normal immune system. The degree of leukocytosis which is considered significant for severe disease and how it is scored vary amongst scoring indices. None of the scores have been prospectively validated, and while total WBC count is useful to estimate the magnitude of the host response in most patient populations, in immune-compromised patients like those receiving chemotherapy, solid organ transplant patients or hematopoietic stem cell transplants the WBC response can be variable or even absent making this marker of severity difficult to interpret. Other cellular subsets like neutrophils, eosinophils and lymphocytes provide important information about the host immune status and play an important role in the immune response against C. difficile infection. However, under the current scoring systems the role of these cellular subsets have been underestimated and only total white blood cell counts are taken into account. In this review we highlight the role of host leukocyte response to C. difficile challenge in the normal and immunocompromised host, and propose possible ways that would allow for a better representation of the different immune cell subsets (neutrophils, lymphocytes and eosinophils) in the current scoring indices.


Assuntos
Infecções por Clostridium/imunologia , Infecções por Clostridium/patologia , Hospedeiro Imunocomprometido , Leucócitos/imunologia , Leucocitose/patologia , Infecções por Clostridium/complicações , Humanos , Estudos Prospectivos
12.
Support Care Cancer ; 23(3): 841-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25218607

RESUMO

PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, cancer treatment may have to be interrupted or delayed. In this study, we looked beyond OM's known risk factors of renal function and melphalan dose with a genome-wide association study (GWAS) to evaluate whether genetic variants in conjunction with clinical risk factors influence predisposition for OM. METHODS: Genotyping was performed using Illumina HumanOmni1-Quad v1.0 BeadChip and further assessed for data quality. We tested 892,589 germline single-nucleotide polymorphisms (SNPs) for association with OM among 972 Caucasian patients treated with high-dose melphalan and ASCT in Total Therapy clinical trials (TT2, TT3, TT4) for newly diagnosed MM. Statistical analyses included t tests, stepwise regression modeling, and logistic regression modeling to find baseline clinical factors and genotypes associated with OM. RESULTS: We found that 353 (36.3 %) patients had grades 2-4 OM. Type of treatment protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2-4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were associated with grades 2-4 OM. The addition of these SNPs increased sensitivity in detecting grades 2-4 OM cases to 52 %. CONCLUSIONS: These SNPs may be important for their roles in inflammatory pathways, epithelial healing, and chemotherapy detoxification.


Assuntos
Antineoplásicos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Estomatite/induzido quimicamente , Estomatite/genética , Adulto , Idoso , Terapia Combinada , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Genótipo , Humanos , Quimioterapia de Indução/efeitos adversos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Fatores de Risco , Transplante Autólogo
13.
Biosens Bioelectron ; 257: 116292, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38653014

RESUMO

We report the development and initial validation of a paper-based nucleic acid testing platform that integrates Loop-mediated isothermal amplification (LAMP) with clustered regularly interspaced short palindromic repeats (CRISPR) technology, referred to as PLACID (Paper-based LAMP-CRISPR Integrated Diagnostics). LAMP eliminates the need for thermal cycling, resulting in simplified instrumentation, and the CRISPR-associated protein (Cas 12a) system eliminates false positive signals from LAMP products, resulting in highly selective and sensitive assays. We optimized the assay to perform both amplification and detection entirely on paper, eliminating the need for complex fluid handling steps and lateral flow assay transfers. Additionally, we engineered a smartphone-operated system that includes a low-powered, non-contact IR heating chamber to actuate paper-based LAMP and CRISPR reactions and enable the detection of fluorescent signals from the paper. The platform demonstrates high specificity and sensitivity in detecting nucleic acid targets with a limit of detection of 50 copies/µL. We integrate an equipment-free sample preparation separation technology designed to streamline the preparation of crude samples prior to nucleic acid testing. The practical utility of our platform is demonstrated by the successful detection of spiked SARS-CoV-2 RNA fragments in saliva, E. Coli in soil, and pathogenic E. Coli in clinically fecal samples of infected patients. Furthermore, we demonstrate that the paper-based LAMP CRISPR chips employed in our assays possess a shelf life of several weeks, establishing them as viable candidates for on-site diagnostics.


Assuntos
Técnicas Biossensoriais , COVID-19 , Sistemas CRISPR-Cas , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Papel , SARS-CoV-2 , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Humanos , Técnicas Biossensoriais/métodos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , COVID-19/virologia , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/instrumentação , Sistemas CRISPR-Cas/genética , Limite de Detecção , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Desenho de Equipamento , Teste de Ácido Nucleico para COVID-19/métodos , Teste de Ácido Nucleico para COVID-19/instrumentação , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Proteínas Associadas a CRISPR/genética , Smartphone
14.
Transplantation ; 108(3): 759-767, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38012862

RESUMO

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.


Assuntos
Infecções por HIV , Transplante de Rim , Humanos , Masculino , Listas de Espera , Rim , Doadores de Tecidos , Transplante de Rim/efeitos adversos , Doadores Vivos , Transplantados , Infecções por HIV/diagnóstico
15.
Cancer Med ; 12(3): 2945-2957, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056757

RESUMO

BACKGROUND AND AIMS: Colorectal cancer (CRC) incidence is increasing in young patients without a clear etiology. Emerging data have implicated the fecal microbiome in CRC carcinogenesis. However, its impact on young onset CRC is poorly defined. METHODS: We performed a meta-analysis of fecal metagenomics sequencing data from n = 692 patients with CRC and n = 602 healthy controls from eleven studies to evaluate features of the fecal metagenome associated with CRC. We hypothesized that known carcinogenic virulence factors (colibactin, fadA) and species abundance may be differentially enriched in young CRC patients relative to older CRC patients and controls. RESULTS: Summary odds ratios (OR) for CRC were increased with the presence of colibactin (OR 1.92 95% CI 1.08-3.38), fadA (OR 4.57 95% CI 1.63-12.85), and F. nucleatum (OR 6.93 95% CI 3.01-15.96) in meta-analysis models adjusted for age, gender, and body mass index. The OR for CRC for the presence of E.coli was 2.02 (0.92-4.45). An increase in the prevalence of Fusobacterium nucleatum (OR = 1.40 [1.18; 1.65]) and Escherichia coli (OR = 1.14 [1.02; 1.28]) per 10-year increase in age was observed in models including samples from both CRC and healthy controls. Species relative abundance was differentially enriched in young CRC patients for five species-Intestinimonas butyriciproducens, Holdemania filiformis, Firimicutues bacterium CAG 83, Bilophilia wadsworthia, and Alistipes putredinis. CONCLUSION: In this study, we observed strong associations with CRC status for colibactin, fadA, and Fusobacterium nucleatum with CRC relative to controls. In addition, we identified several microbial species differentially enriched in young colorectal cancer patients. Studies targeting the young CRC patients are warranted to elucidate underlying preclinical mechanisms.


Assuntos
Neoplasias Colorretais , Microbiota , Humanos , Neoplasias Colorretais/genética , Metagenoma , Metagenômica , Fusobacterium nucleatum , Carcinogênese/genética
16.
Pulm Circ ; 12(1): e12051, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35506110

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive, ultimately fatal cardiopulmonary disease associated with a number of physiologic changes, which is believed to result in imbalances in the intestinal microbiota. To date, comprehensive investigational analysis of the intestinal microbiota in human subjects is still limited. To address this, we performed a pilot study of the intestinal microbiome in 20 PAH and 20 non-PAH healthy control subjects, recruited from a single center, with each PAH subject recruited simultaneously with a cohabitating non-PAH control subject. Shotgun metagenomic sequencing was used to analyze the microbiome profiles. There were no differences between PAH and non-PAH subjects across several measures of microbial abundance and diversity (Alpha Diversity, Beta Diversity, F/B ratio). The relative abundance of Lachnospiraceae bacterium GAM79 was lower in PAH stool samples as compared to non-PAH control subject' stool. There was no strong or reproducible association between PAH disease severity and global microbial abundance, but several bacterial species (a relative abundance of Anaerostipes rhamnosivorans and a relative deficiency of Amedibacterium intestinale, Ruminococcus bicirculans, and Ruminococcus albus species were associated with disease severity (most proximal right heart catheterization hemodynamics and six-minute walk test distance) in PAH subjects. Our results support further investigation into the presence, significance, and potential physiologic effects of a PAH-specific intestinal microbiome.

17.
Open Forum Infect Dis ; 9(4): ofac045, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35355893

RESUMO

Background: Ocular candidiasis is a known complication of candidemia. Given the poor ocular penetration of echinocandins, there is some concern that the increasing use of echinocandins may portend an increased incidence of ophthalmic complications. We examined the changing trends in antifungal prescribing patterns and the incidence of ophthalmic complications after candidemia. Methods: Patients with blood cultures positive for Candida species between January 2014 and June 2020 who underwent screening fundoscopic examination by an ophthalmologist were analyzed. The χ2 analysis was used to compare antifungal prescriptions and ocular exam findings before and after 2016. Trend analysis was also performed to assess temporal changes in prescribing practices and eye exam findings. Results: There were 226 candidemia cases during the study period, 129 (57.1%) of which underwent screening eye exams. From 2014 to 2015, 24 of 37 (64.5%) patients received eye-penetrating antifungals compared to 36 of 92 (39.1%) from 2016 to 2020 (P = .008). Overall, 30 of 129 (23.3%) patients had abnormal eye exams with the prevalence of abnormal findings being 7 of 37 (18.9%) before 2016 compared to 23 of 92 (25%, P = .46) thereafter. A trend analysis revealed an increase in abnormal eye findings over the study period (P = .008). Of the 30 patients who had abnormal eye exams, 9 (30%) had a change in systemic antifungal therapy from echinocandins to eye-penetrating antifungals. Echinocandin use was associated with abnormal eye findings. Conclusions: Prescription of eye-penetrating antifungals for candidemia has trended down since 2016. This was associated with a concomitant increase in abnormal findings on screening fundoscopy. Abnormal eye exams were not uncommon throughout our study period.

19.
Respir Med ; 178: 106313, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33550152

RESUMO

BACKGROUND: Ecological evidence suggests that exposure to air pollution affects coronavirus disease 2019 (COVID-19) outcomes. However, no individual-level study has confirmed the association to date. METHODS: We identified COVID-19 patients diagnosed at the University of Cincinnati hospitals and clinics and estimated particulate matter ≤2.5 µm (PM2.5) exposure over a 10-year period (2008-2017) at their residential zip codes. We used logistic regression to evaluate the association between PM2.5 exposure and hospitalizations for COVID-19, adjusting for socioeconomic characteristics and comorbidities. RESULTS: Among the 1128 patients included in our study, the mean (standard deviation) PM2.5 was 11.34 (0.70) µg/m3 for the 10-year average exposure and 13.83 (1.03) µg/m3 for the 10-year maximal exposures. The association between long-term PM2.5 exposure and hospitalization for COVID-19 was contingent upon having pre-existing asthma or chronic obstructive pulmonary (COPD) (Pinteraction = 0.030 for average PM2.5 and Pinteraction = 0.001 for maximal PM2.5). In COVID-19 patients with asthma or COPD, the odds of hospitalization were 62% higher with 1 µg/m3 increment in 10-year average PM2.5 (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.00-2.64) and 65% higher with 1 µg/m3 increase in 10-year maximal PM2.5 levels (OR: 1.65, 95% CI: 1.16-2.35). However, among COVID-19 patients without asthma or COPD, PM2.5 exposure was not associated with higher hospitalizations (OR: 0.84, 95% CI: 0.65-1.09 for average PM2.5 and OR: 0.78, 95% CI: 0.65-0.95 for maximal PM2.5). CONCLUSIONS: Long-term exposure to PM2.5 is associated with higher odds of hospitalization in COVID-19 patients with pre-existing asthma or COPD.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , COVID-19/epidemiologia , Exposição Ambiental/efeitos adversos , Hospitalização/estatística & dados numéricos , Material Particulado/efeitos adversos , Adulto , Asma/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores Socioeconômicos , Fatores de Tempo
20.
medRxiv ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32817977

RESUMO

Blood type purportedly influences susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but whether it affects severity of coronavirus disease 2019 (COVID-19) is unclear. Therefore, we examined the association of blood type and rhesus with hospitalization and disease severity among 428 COVID-19 patients diagnosed at the University of Cincinnati health system. In the sample, 50.2% of participants had the blood type O, 38.7% had the blood type A, 17.5% had the blood type B, and 3.5% had the blood type AB. In analysis adjusted for sociodemographic characteristics and comorbidities, the blood types A (OR: 0.90, 95% CI: 0.54, 1.50), B (OR: 0.93, 95% CI: 0.51, 1.69), AB (OR: 0.69, 95% CI: 0.20, 2.41), and O (OR: 1.18, 95%: 0.74, 1.98) were not associated with hospitalization for COVID-19. Similarly, the blood types A (OR: 0.93, 95% CI: 0.52, 1.65), B (OR: 0.92, 95% CI: 0.46, 1.84), AB (OR: 0.30, 95% CI: 0.04, 2.44), and O (OR: 1.25, 95%: 0.73, 2.14) were not associated with admission to intensive care unit or death in COVID-19. In conclusion, blood type is not associated with hospitalization or disease severity in COVID-19; therefore, it may not be useful marker for identifying patients at risk for severe COVID-19.

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