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A global metagenomic map of urban microbiomes and antimicrobial resistance

Danko, David; Bezdan, Daniela; Afshin, Evan E; Ahsanuddin, Sofia; Bhattacharya, Chandrima; Butler, Daniel J; Chng, Kern Rei; Donnellan, Daisy; Hecht, Jochen; Jackson, Katelyn; Kuchin, Katerina; Karasikov, Mikhail; Lyons, Abigail; Mak, Lauren; Meleshko, Dmitry; Mustafa, Harun; Mutai, Beth; Neches, Russell Y; Ng, Amanda; Nikolayeva, Olga; Nikolayeva, Tatyana; Png, Eileen; Ryon, Krista A; Sanchez, Jorge L; Shaaban, Heba; Sierra, Maria A; Thomas, Dominique; Young, Ben; Abudayyeh, Omar O; Alicea, Josue; Bhattacharyya, Malay; Blekhman, Ran; Castro-Nallar, Eduardo; Cañas, Ana M; Chatziefthimiou, Aspassia D; Crawford, Robert W; De Filippis, Francesca; Deng, Youping; Desnues, Christelle; Dias-Neto, Emmanuel; Dybwad, Marius; Elhaik, Eran; Ercolini, Danilo; Frolova, Alina; Gankin, Dennis; Gootenberg, Jonathan S; Graf, Alexandra B; Green, David C; Hajirasouliha, Iman; Hastings, Jaden J A; Hernandez, Mark; Iraola, Gregorio; Jang, Soojin; Kahles, Andre; Kelly, Frank J; Knights, Kaymisha; Kyrpides, Nikos C; Łabaj, Paweł P; Lee, Patrick K H; Leung, Marcus H Y; Ljungdahl, Per O; Mason-Buck, Gabriella; McGrath, Ken; Meydan, Cem; Mongodin, Emmanuel F; Moraes, Milton Ozorio; Nagarajan, Niranjan; Nieto-Caballero, Marina; Noushmehr, Houtan; Oliveira, Manuela; Ossowski, Stephan; Osuolale, Olayinka O; Özcan, Orhan; Paez-Espino, David; Rascovan, Nicolás; Richard, Hugues; Rätsch, Gunnar; Schriml, Lynn M; Semmler, Torsten; Sezerman, Osman U; Shi, Leming; Shi, Tieliu; Siam, Rania; Song, Le Huu; Suzuki, Haruo; Court, Denise Syndercombe; Tighe, Scott W; Tong, Xinzhao; Udekwu, Klas I; Ugalde, Juan A; Valentine, Brandon; Vassilev, Dimitar I; Vayndorf, Elena M; Velavan, Thirumalaisamy P; Wu, Jun; Zambrano, María M; Zhu, Jifeng; Zhu, Sibo; Mason, Christopher E
We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
PMID: 34043940
ISSN: 1097-4172
CID: 4888252

Integration of Gender-Affirming Primary Care and Peer Navigation With HIV Prevention and Treatment Services to Improve the Health of Transgender Women: Protocol for a Prospective Longitudinal Cohort Study

Lama, Javier R; Mayer, Kenneth H; Perez-Brumer, Amaya G; Huerta, Leyla; Sanchez, Hugo; Clark, Jesse L; Sanchez, Jorge; Reisner, Sari L
BACKGROUND:Public health strategies are urgently needed to improve HIV disparities among transgender women, including holistic intervention approaches that address those health needs prioritized by the community. Hormone therapy is the primary method by which many transgender women medically achieve gender affirmation. Peer navigation has been shown to be effective to engage and retain underserved populations living with HIV in stable primary medical care. OBJECTIVE:This study aims to assess the feasibility and acceptability of an integrated innovative HIV service delivery model designed to improve HIV prevention and care by combining gender-affirming primary care and peer navigation with HIV prevention and treatment services. METHODS:A 12-month, nonrandomized, single-arm cohort study was implemented in Lima, Peru, among adult individuals, assigned a male sex at birth, who identified themselves as transgender women, regardless of initiation or completion of medical gender affirmation, and who were unaware of their HIV serostatus or were living with HIV but not engaged in HIV treatment. HIV-negative participants received quarterly HIV testing and were offered to initiate pre-exposure prophylaxis. HIV-positive participants were offered to initiate antiretroviral treatment and underwent quarterly plasma HIV-1 RNA and peripheral CD4+ lymphocyte cell count monitoring. All participants received feminizing hormone therapy and adherence counseling and education on their use. Peer health navigation facilitated retention in care by visiting participants at home, work, or socialization venues, or by contacting them by social media and phone. RESULTS:Patient recruitment started in October 2016 and finished in March 2017. The cohort ended follow-up on March 2018. Data analysis is currently underway. CONCLUSIONS:Innovative and culturally sensitive strategies to improve access to HIV prevention and treatment services for transgender women are vital to curb the burden of HIV epidemic for this key population. Findings of this intervention will inform future policies and research, including evaluation of its efficacy in a randomized controlled trial. TRIAL REGISTRATION/ NCT03757117; INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:DERR1-10.2196/14091.
PMID: 31250829
ISSN: 1929-0748
CID: 4090042

Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy

Luen, S J; Salgado, R; Dieci, M V; Vingiani, A; Curigliano, G; Gould, R E; Castaneda, C; D'Alfonso, T; Sanchez, J; Cheng, E; Andreopoulou, E; Castillo, M; Adams, S; Demaria, S; Symmans, W F; Michiels, S; Loi, S
BACKGROUND:For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC. PATIENTS AND METHODS:We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs. RESULTS:A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10-40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79-0.92; P < 0.001), and improved OS (HR: 0.87; 95% CI 0.80-0.94; P < 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P < 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (PInt=0.003) and OS (PInt=0.008) with a greater magnitude of positive effect observed for RCB class II than class III. CONCLUSIONS:TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.
PMID: 30590484
ISSN: 1569-8041
CID: 4340192

Central Respiratory Depression In Lupus Rhomboencephalitis [Meeting Abstract]

Ramirez, CBernabe; Ramesh, N; Sanchez, J; Filopei, J; Bergman, M; Patton, E; Sulica, R
ISSN: 1535-4970
CID: 2520112

Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles

Goepfert, Paul A; Elizaga, Marnie L; Seaton, Kelly; Tomaras, Georgia D; Montefiori, David C; Sato, Alicia; Hural, John; DeRosa, Stephen C; Kalams, Spyros A; McElrath, M Juliana; Keefer, Michael C; Baden, Lindsey R; Lama, Javier R; Sanchez, Jorge; Mulligan, Mark J; Buchbinder, Susan P; Hammer, Scott M; Koblin, Beryl A; Pensiero, Michael; Butler, Chris; Moss, Bernard; Robinson, Harriet L
BACKGROUND:Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected adults for safety, immunogenicity, and 6-month durability of immune responses. METHODS:A total of 299 individuals received 2 doses of JS7 DNA vaccine and 2 doses of MVA/HIV62B at 0, 2, 4, and 6 months, respectively (the DDMM regimen); 3 doses of MVA/HIV62B at 0, 2, and 6 months (the MMM regimen); or placebo injections. RESULTS:At peak response, 93.2% of the DDMM group and 98.4% of the MMM group had binding antibodies for Env. These binding antibodies were more frequent and of higher magnitude for the transmembrane subunit (gp41) than the receptor-binding subunit (gp120) of Env. For both regimens, response rates were higher for CD4(+) T cells (66.4% in the DDMM group and 43.1% in the MMM group) than for CD8(+) T cells (21.8% in the DDMM group and 14.9% in the MMM group). Responding CD4(+) and CD8(+) T cells were biased toward Gag, and >70% produced 2 or 3 of the 4 cytokines evaluated (ie, interferon γ, interleukin 2, tumor necrosis factor α, and granzyme B). Six months after vaccination, the magnitudes of antibodies and T-cell responses had decreased by <3-fold. CONCLUSIONS:DDMM and MMM vaccinations with virus-like particle-expressing immunogens elicited durable antibody and T-cell responses.
PMID: 24403557
ISSN: 1537-6613
CID: 3242012

Combination antiretroviral treatment for women previously treated only in pregnancy: week 24 results of AIDS clinical trials group protocol a5227

Vogler, Mary A; Smeaton, Laura M; Wright, Rodney L; Cardoso, Sandra W; Sanchez, Jorge; Infante, Rosa; Moran, Laura E; Godfrey, Catherine; Demeter, Lisa M; Johnson, Victoria A
BACKGROUND: Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). METHODS: Nonpregnant women with plasma HIV-1 RNA of >/=500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for >/=24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks. RESULTS: Fifty-four women were enrolled between October 2007 and December 2009; 52 of 54 completed 24 weeks of follow-up. Median baseline CD4 T-cell count was 265/mm and baseline plasma HIV-1 RNA was 4.6 log10 copies per milliliter. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42 of 52 women or 81% (exact 95% confidence interval: 68% to 90%). There were no differences in response by country, by number, or class of prior pMTCT exposures. Although confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence. CONCLUSIONS: In this first prospective clinical trial studying combination antiretroviral retreatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported nonadherence.
PMID: 24759064
ISSN: 1525-4135
CID: 908112

Clinical and dermoscopic patterns of melanocytic nevi in Hispanic adolescents: a descriptive study

Sosa-Seda, Ivette M; Valentin-Nogueras, Sheila; Figueroa, Luz D; Sanchez, Jorge L; Mercado, Rogelio
BACKGROUND: Melanocytic nevi are well-known, important precursors of melanoma among children and adults. The adolescence period is an important period for nevi formation and evolution. This study provides data of a longitudinal study of nevi in a Hispanic adolescent population. MATERIALS AND METHODS: A cross-sectional survey and 1-year prospective follow-up study was performed on Hispanic students from grades 6 and 7 at a school in Caguas, Puerto Rico (n = 90). The survey was completed by the students and one of their parents. The backs of the children were clinically examined for melanocytic nevi using digital photography and dermoscopy. Follow-up was conducted one year later. RESULTS: The study cohort consisted of 53 (59%) boys and 37 (41%) girls, with an average age of 11.9 years (range 11-13 years). At the beginning of the study, 85% (n = 71/90) of the students presented with melanocytic nevi on their backs. After one year, new nevi were identified in 62% (n = 44/71), and there was a mean increase in nevus count of 1.8 (P < 0.001). A trend toward increased nevus count in lighter skin types was observed (P < 0.001). The predominant dermoscopic pattern was reticular (44%). The globular pattern was found most commonly in children with skin-type II (100%), while the reticular pattern was the most common among skin-types III (32%), IV (56%), and V (45%). CONCLUSIONS: This study supports the utility of digital photography and dermoscopy for the evaluation of melanocytic nevi, providing evidence of the interrelationship between nevus count, dermoscopic pattern, and skin phenotype.
PMID: 23968120
ISSN: 0011-9059
CID: 759022

Follicular mucinosis presenting as an acneiform eruption: a follow-up study

Brau-Javier, Cristina N; Santos-Arroyo, Aileen E; De Sanctis-Gonzalez, Ivette M; Sanchez, Jorge L
It has been proposed by many authors that follicular mucinosis is directly associated with mycosis fungoides (MF). Follicular mucinosis may be classified into 3 main clinical variants: a benign idiopathic form in children and young adults, which includes an acneiform presentation; an idiopathic form in older patients with a benign course; and a third variant that occurs in adults and is associated with MF. Our goal was to study the relationship between the acneiform variant of follicular mucinosis and MF. Eight patients previously diagnosed with the acneiform variant of follicular mucinosis were identified. Biopsy specimens were reviewed to evaluate the histopathologic attributes that characterize the disease and the infiltrate's immunohistochemistry. Also, patient follow-up was assessed to evaluate the clinical course of the disease. Median age of onset of disease was 29.5 years; 95% of lesions were located in the head and neck region. Biopsy specimens showed a moderate to dense perivascular, perifollicular, and interstitial infiltrate of lymphocytes with mucinous deposits within the follicular epithelium. On immunohistochemistry, the infiltrate showed prominent leukocyte common antigen (LCA) positivity and a CD3-positive and CD4-positive infiltrate with rare CD20-positive cells. None of the study patients showed evidence of MF after a mean follow-up of 3 years. The benign course of disease demonstrated in the study patients suggests that the acneiform variant of follicular mucinosis probably represents a subpopulation of the benign idiopathic form of the disease. However, given that histopathologically this variant cannot be distinguished from the lymphoma-associated variant of follicular mucinosis, longitudinal evaluation is still warranted in these patients.
PMID: 24257190
ISSN: 0193-1091
CID: 759042

Langerhans cell sarcoma: a case report [Case Report]

Valentin-Nogueras, Sheila M; Seijo-Montes, Rachelle; Montalvan-Miro, Elena; Sanchez, Jorge L
Primary cutaneous neoplasms of histiocytes and dendritic cells are rare. Langerhans cells are a subset of antigen-presenting dendritic cells. Neoplasms of Langerhans cells are classified into cytologically benign Langerhans cell histiocytosis and cytologically malignant Langerhans cell sarcoma. Langerhans cell sarcoma is a rare entity characterized by multiorgan involvement and an aggressive clinical course. To date, only 30 cases of Langerhans cell sarcoma, including the present case, have been reported. We report a new case of Langerhans cell sarcoma that presented with multifocal cutaneous involvement. Diagnosis was done based on histopathological, immunohistochemical evaluation, as well as ultrastructural analysis identifying the presence of Birbeck granules. Our case represents a new case of this extremely rare, overtly aggressive neoplasm of Langerhans cells. Within 2 years of diagnosis, the patient developed metastatic disease and consequently died. Early recognition is important because of the tendency of Langerhans cell sarcoma to recur and metastasize. Therefore, ancillary techniques such as immunohistochemical and ultrastructural studies to confirm the diagnosis are very advantageous.
PMID: 23590692
ISSN: 0303-6987
CID: 759012

Organizing a dermatology service mission

Ramirez-Fort, Marigdalia K; Lastra-Vicente, Rosana; Levitt, Jacob O; Sanchez, Jorge L; Reizner, George T
BACKGROUND: There are few published guidelines that describe the forethought and logistical considerations needed to create a dermatology-specific medical mission. OBJECTIVE: To report the experience of planning and executing a successful medical mission to an underserved community in Puerto Rico. METHODS: We identified an area of need and projected the volume of patients and diseases to be treated. After recruiting medical staff, pharmaceutical and surgical supplies were collected. Important concerns included establishing the scope of medical and educational services to be rendered, advertising the clinic, arranging for biopsy processing, ensuring follow-up, and selecting a method for medical documentation. We tracked the number of patients seen, diagnoses made, and materials used to prepare for future missions. RESULTS: We recruited 12 physicians and 25 ancillary (i.e. nonlicensed physician) staff members, including: six dermatologists, four internists, one pathologist, one psychiatrist, 23 medical students, and two medical assistants. We secured 12 examination rooms in an existing medical facility. Two pharmaceutical companies and two pathology companies provided the medications and surgical supplies with the remainder coming from the volunteer physicians' offices. Three thousand dollars were raised and used toward purchasing additional supplies. Advertising via public announcements resulted in the attendance of 166 patients during the 1-day clinic. A total of 41 procedures were performed, including 14 biopsies, five excisions, three incisions and drainage, and 19 electrodessications and curettage. CONCLUSION: Proper planning is critical in creating a successful dermatology mission. Documenting the care given and supplies used helps to identify needs and optimize limited resources for future missions. The goal of a self-sustaining public health service starts with patient education and coordination with the local healthcare providers.
PMID: 23113920
ISSN: 0011-9059
CID: 759002