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1.
Nat Med ; 30(8): 2170-2180, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38942992

ABSTRACT

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B+ natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B+ NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.


Subject(s)
Liver Neoplasms , Liver , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/surgery , Liver Neoplasms/secondary , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Male , Female , Middle Aged , Aged , Liver/pathology , Liver/metabolism , Biopsy , Neoplasm Staging , Pancreatectomy , Extracellular Traps/metabolism , Prognosis
2.
Int J Gen Med ; 15: 6881-6885, 2022.
Article in English | MEDLINE | ID: mdl-36061958

ABSTRACT

During the COVID-19 pandemic, adults with chronic conditions delayed or avoided seeking preventative and general medical care, leading to adverse consequences for morbidity and mortality. In order to bring patients back into care, we, in this qualitative study, sought to understand the foremost health-related needs of our multi-morbid ambulatory patients to inform future outreach interventions. Via a telephone-based survey of our high-risk patients, defined using a validated EPIC risk model for hospitalization and ED visits, we surveyed 214 participants an open-ended question, "What is your top health concern that you would like to speak with a doctor or nurse about". We found 4 major themes: 1) primary care matters, 2) disruptions in health care, 3) COVID-19's impact on physical and mental health, and 4) amplified social vulnerabilities. Our results suggest that interventions that reduce barriers to preventative services and disruptions to healthcare delivery are needed.

3.
AIDS Care ; 31(12): 1585-1592, 2019 12.
Article in English | MEDLINE | ID: mdl-31131623

ABSTRACT

In the United States, 15% of HIV-positive individuals do not know their HIV serostatus. While CDC guidelines recommend HIV testing for individuals age 13-64 years, racial and ethnic minorities continue to experience delays in HIV diagnosis. We assessed providers' perspectives on HIV testing at an urban community health center serving racial/ethnic minority populations of low socioeconomic status. We conducted five focus groups from January 2017 to November 2017 with 74 health center staff: 20 adult medicine/primary care providers, 34 community health workers (CHWs) and community health administrators, six urgent care physicians, and fourteen behavioral health providers. Study staff analyzed transcripts using a grounded theory approach and used open coding to develop themes. We identified five themes affecting HIV testing: 1) provider perception of patients' preferences for HIV testing; 2) competing medical and social issues; 3) inter-professional communication; 4) knowledge of clinical indicators for HIV testing; and 5) knowledge of frequency of HIV testing. Primary care physicians desired mechanisms to easily identify patients for HIV testing and assistance with testing for non-English speakers. Training to improve comfort with HIV testing, integrating CHWs into routine practice, and focusing on patients' cultural beliefs may increase HIV testing in diverse community health centers..


Subject(s)
Community Health Centers , Community Health Workers/psychology , Cultural Competency , HIV Infections/diagnosis , Interprofessional Relations , Mass Screening/methods , Physicians/psychology , Adult , Female , Focus Groups , HIV Infections/ethnology , Health Knowledge, Attitudes, Practice , Humans , Male , Mass Screening/organization & administration , Middle Aged , Patient Preference , Perception , Public Health , Qualitative Research , United States
4.
AIDS Behav ; 23(4): 835-846, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30737609

ABSTRACT

Latino immigrants with substance use and mental health problems are at risk for undiagnosed HIV and sexually transmitted infections (STIs). Participants in a randomized control trial were recruited in Boston, USA and Madrid and Barcelona, Spain. Eligibility criteria were Latino self-identification, age 18-70, elevated substance use and mental health symptoms, and not currently in substance or mental health care. A multinomial logistic regression examined predictors of HIV/STI testing decline and lost to follow-up (LTFU) prior to testing compared with acceptance. Of 341 participants, 74% accepted testing, 4% declined, and 22% were LTFU. The odds of LTFU were higher in those with high concern for HIV and those whose main partner had done HIV testing. Age ≥ 35 years, females, higher education, and higher report of discrimination lowered the odds of LTFU. Delivery of HIV/STI testing through community agencies and outreach could overcome barriers to HIV/STI diagnosis in this population of Latinos.Clinical Trial Number: NCT02038855.


Subject(s)
Emigrants and Immigrants/statistics & numerical data , HIV Infections/diagnosis , Hispanic or Latino/statistics & numerical data , Mass Screening/statistics & numerical data , Mental Disorders/psychology , Patient Acceptance of Health Care/psychology , Sexually Transmitted Diseases/diagnosis , Substance-Related Disorders/psychology , Adolescent , Adult , Aged , Boston/epidemiology , Female , HIV Infections/ethnology , HIV Infections/psychology , Humans , Lost to Follow-Up , Male , Mental Disorders/ethnology , Mental Health , Middle Aged , Patient Acceptance of Health Care/ethnology , Serologic Tests , Sexual Partners , Sexually Transmitted Diseases/ethnology , Sexually Transmitted Diseases/psychology , Spain/epidemiology , Substance-Related Disorders/ethnology
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