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1.
Nat Commun ; 12(1): 5955, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34642316

RESUMEN

Leptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials. Here, we investigate the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We recover immune and malignant cell types in the CSF, characterize cell behavior changes following ICI, and identify genomic features associated with relevant clinical phenomena. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and demonstrates clinical utility of cell-free and single-cell genomic measurements for LMD research.

2.
Nat Commun ; 12(1): 5954, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34642329

RESUMEN

Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.

3.
J Clin Med ; 10(20)2021 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-34682880

RESUMEN

The use of heated intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery has been gaining increasing traction in treating gastric adenocarcinoma with metastasis to the peritoneum in recent years. The addition of laparoscopic HIPEC (LS-HIPEC) to these treatment algorithms has increased the flexibility and adaptability of HIPEC integrating into treatment sequencing, allowing for iterative protocols of LS-HIPEC prior to cytoreduction as neoadjuvant treatment, as well as in the palliation of patients with unresectable disease and uncontrolled ascites. As the use of HIPEC in gastric adenocarcinoma continues to be refined, LS-HIPEC algorithms should continue to be considered and utilized both in curative treatment algorithms as well as in patients in the palliative setting. Given that LS-HIPEC remains a relatively nascent treatment modality, we advocate for its use in the setting of a clinical trial when feasible.

4.
Pastoral Psychol ; : 1-20, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34483371

RESUMEN

The aim of this study was to evaluate the psychometric evidence of the original and short versions of the Santa Clara Strength of Religious Faith Questionnaire (SCSRFQ) in Spanish in a sample of 245 Peruvian adolescents and adults (mean age = 21.04 years, SD = 3.07, 47.8% male and 52.2% female), selected by nonprobabilistic convenience sampling. Additionally, the Coronavirus Anxiety Scale and the Satisfaction with Life Scale were applied. Confirmatory Factor Analysis, internal consistency reliability methods, hierarchical sequence of variance models, and a graded response model were used. Results indicate that both versions of the SCSRFQ showed robust psychometric properties: adequate unidimensional structure, adequate difficulty and discrimination parameters, and significant relationships with the measures of fear of COVID-19 and satisfaction with life. The original version of the SCSRFQ showed evidence of strict measurement invariance by sex and age, whereas the short version showed strict invariance by sex and configural invariance by age. Both versions showed acceptable reliability indices. In conclusion, the original and short versions of the SCSRFQ in Spanish show evidence of psychometric indicators that support their use to assess the strength of religious faith.

5.
J Gastrointest Surg ; 2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34506017

RESUMEN

Surgeons encounter neutropenic patients through elective or emergency consultation with increasing regularity. As medical management continues to extend the lives of patients with benign hematologic diseases, hematologic malignancies, solid malignancies, or iatrogenic neutropenia, more patients are presenting with infectious complications caused and/or complicated by their neutropenia. This leaves surgeons in the difficult position of managing medically fragile patients with unusual presentations of common disease processes. These patients often fall outside of classical guidelines and treatment pathways. Many studies addressing these issues are retrospective and non-randomized. Here, we review common emergency gastrointestinal surgery scenarios and their management in the setting of a neutropenic patient. While biliary disease, appendicitis, anorectal disease, and perforations will be covered in detail, an extensive appreciation of a patient's medical or oncologic disease course and appropriate utilization of consultants such as interventional radiology, gastroenterology, and hematology is often necessary.

6.
Elife ; 102021 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-34486522

RESUMEN

Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF cone-rod homeobox (CRX) in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. The ability of information content to distinguish enhancers and silencers targeted by the same TF illustrates how motif context determines the activity of cis-regulatory sequences.


Asunto(s)
Células Fotorreceptoras/fisiología , Factores de Transcripción/metabolismo , Animales , Sitios de Unión , Femenino , Masculino , Ratones , Unión Proteica , Retina/citología , Retina/fisiología , Factores de Transcripción/genética
7.
Cancer Cell ; 39(10): 1404-1421.e11, 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34520734

RESUMEN

The CDK4/6 inhibitor, palbociclib (PAL), significantly improves progression-free survival in HR+/HER2- breast cancer when combined with anti-hormonals. We sought to discover PAL resistance mechanisms in preclinical models and through analysis of clinical transcriptome specimens, which coalesced on induction of MYC oncogene and Cyclin E/CDK2 activity. We propose that targeting the G1 kinases CDK2, CDK4, and CDK6 with a small-molecule overcomes resistance to CDK4/6 inhibition. We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. Together with the clinical analysis, MYC activity predicts (PF3600) efficacy across multiple cell lineages. Finally, we find that CDK2/4/6 inhibition does not compromise tumor-specific immune checkpoint blockade responses in syngeneic models. We anticipate that (PF3600), currently in phase 1 clinical trials, offers a therapeutic option to cancer patients in whom CDK4/6 inhibition is insufficient to alter disease progression.

8.
Blood ; 2021 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-34424963

RESUMEN

Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity (IEI). Despite an improved understanding of genetic defects in pES, the underlying immunobiology of pES is poorly defined, and characteristic diagnostic immune parameters are lacking. We describe the immune characteristics of 24 patients with pES and compared them with 22 patients with chronic immune thrombocytopenia (cITP) and 24 healthy controls (HC). Compared to patients with cITP and HC, patients with pES had increased circulating T-follicular helper cells (cTfh), increased T cell activation, and decreased naïve CD4+ T cells for age. Despite normal or high IgG in the majority of pES at presentation, class-switched memory B cells (CSMB) were decreased. Within the cTfh subset, we noted features of post-activation exhaustion with upregulation of several canonical checkpoint inhibitors. TCR-b repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HC. Among patients with pES, those without a known gene defect had a similar characteristic immune abnormality as patients with defined genetic defects. Similarly, patients with pES with normal IgG had similar T cell abnormalities as patients with low IgG. Since genetic defects have been identified in only less than half of patients with pES, our findings of similar immune abnormalities across all pES patients help establish a common characteristic immunopathology in pES irrespective of the underlying genetic etiology.

10.
Diabetes Metab Syndr ; 15(5): 102245, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34416467

RESUMEN

AIMS: It is important to have valid and reliable measures to determine the psychological impact of COVID-19 in patients with diabetes; however, few instruments have been developed and validated for this population. Therefore, the aim of this study was to validate the Scale of Worry for Contagion of COVID-19 (PRE-COVID-19) in a sample of patients with diabetes mellitus (DM). MATERIALS AND METHODS: A total of 219 patients (66.2% female, mean age 58.5 SD = 18.2) participated, selected through non-probabilistic sampling. The PRE-COVID-19 and the Generalized Anxiety Disorder Scale-2 were applied. Reliability analysis was performed for internal consistency, structural equation modeling and item response theory modeling. RESULTS: The results show that a unidimensional 5-item model presents satisfactory goodness-of-fit indices and excellent reliability values. Likewise, convergent validity between the PRE-COVID-19 and a measure of anxiety is evident. All items present adequate discrimination parameters, allowing for discerning between those patients with critical concern about COVID-19 contagion from those with severe concern. CONCLUSION: It is concluded that the PRE-COVID-19 is an instrument with adequate psychometric properties to measure concern about COVID-19 infection and the emotional impact in patients with DM.


Asunto(s)
COVID-19/psicología , Diabetes Mellitus Tipo 2/psicología , Psicometría/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/diagnóstico , Ansiedad/epidemiología , Ansiedad/etiología , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/etiología , COVID-19/epidemiología , Cuba/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Psicometría/normas , Encuestas y Cuestionarios , Adulto Joven
11.
J Neurosurg Spine ; : 1-11, 2021 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-34359032

RESUMEN

OBJECTIVE: In a 2014 analysis of orthopedic and neurological surgical case logs published by the Accreditation Council for Graduate Medical Education (ACGME), it was reported that graduating neurosurgery residents performed more than twice the number of spinal procedures in their training compared with graduating orthopedic residents. There has, however, been no follow-up assessment of this trend. Moreover, whether this gap in case volume equates to a similar gap in procedural hours has remained unstudied. Given the association between surgical volume and outcomes, evaluating the status of this disparity has value. Here, the authors assess trends in case volume and procedural hours in adult spine surgery for graduating orthopedic and neurological surgery residents from 2014 to 2019. METHODS: A retrospective analysis of ACGME case logs from 2014 to 2019 for graduating orthopedic and neurological surgery residents was conducted for adult spine surgeries. Case volume was converted to operative hours by using periprocedural times from the 2019 Medicare/Medicaid Physician Fee Schedule. Graduating residents' spinal cases and hours, averaged over the study period, were compared between the two specialties by using 2-tailed Welch's unequal variances t-tests (α = 0.05). Longitudinal trends in each metric were assessed by linear regression followed by cross-specialty comparisons via tests for equality of slopes. RESULTS: From 2014 to 2019, graduating neurosurgical residents logged 6.8 times as many spinal cases as their orthopedic counterparts, accruing 431.6 (95% CI 406.49-456.61) and 63.8 (95% CI 57.08-70.56) cases (p < 0.001), respectively. Accordingly, graduating neurosurgical residents logged 6.1 times as many spinal procedural hours as orthopedic surgery residents, accruing 1020.7 (95% CI 964.70-1076.64) and 166.6 (95% CI 147.76-185.35) hours (p < 0.001), respectively. Over these 5 years, both fields saw a linear increase in graduating residents' adult spinal case volumes and procedural hours, and these growth rates were higher for neurosurgery (+16.2 cases/year vs +4.4 cases/year, p < 0.001; +36.4 hours/year vs +12.4 hours/year, p < 0.001). CONCLUSIONS: Graduating neurosurgical residents accumulated substantially greater adult spinal case volumes and procedural hours than their orthopedic counterparts from 2014 to 2019. This disparity has been widened by a higher rate of growth in adult spinal cases among neurosurgery residents. Accordingly, targeted efforts to increase spinal exposure for orthopedic surgery residents-such as using cross-specialty collaboration-should be explored.

12.
J Burn Care Res ; 2021 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-34427655

RESUMEN

Burn patients have numerous risk factors for multidrug resistant organisms (MDROs) and altered pharmacokinetics, which both independently increase the risk of treatment failure. Data on appropriate antimicrobial dosing are limited in this population and therapeutic drug monitoring (TDM) for beta-lactams is impractical at most facilities. 1-3 Technology is available that can detect genetic markers of resistance, but they are not all encompassing, and often require specialized facilities that can detect less common genetic markers. 4-5 Newer antimicrobials can help combat MDROs, but additional resistance patterns may evolve during treatment. Considering drug shortages and antimicrobial formularies, clinicians must remain vigilant when treating infections. This case report describes the development of resistance to ceftazidime-avibactam in a burn patient. The patient was a 54- year-old burn victim with a 58% total body surface area (TBSA) thermal burn who underwent multiple courses of antibiotics for various Pseudomonal infections. The initial Pseudomonal wound infection was sensitive to cefepime, aminoglycosides, and meropenem. A subsequent resistant pseudomonal pneumonia was treated with ceftazidime-avibactam 2.5 grams every 6 hours due to the elevated MIC to cefepime (16mcg/mL) and meropenem (>8mcg/mL). Although, the patient improved over 7 days, the patient again spiked fevers and had increased white blood counts (WBC). Repeat blood cultures demonstrated a multidrug resistant (MDR) Pseudomonas with a minimum inhibitory concentration (MIC) to ceftazidime-avibactam of 16mcg/mL, which is above the Clinical and Laboratory Standards Institute (CLSI) breakpoint of 8mcg/mL. At first, resistance was thought to have occurred due to inadequate dosing, but genetic work demonstrated multiple genes encoding beta-lactamases.

13.
Nanotechnology ; 32(47)2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34380123

RESUMEN

The structures formed by the deposition of mass-selected niobium oxide clusters, Nb3Oy(y = 5, 6, 7), onto Au(111) were studied by scanning tunneling microscopy. The as-deposited Nb3O7clusters assemble into large dendritic structures that grow on the terraces as well as extend from the top and bottom of step edges. The Nb3O6cluster also forms dendritic assemblies but they are generally much smaller in size. The assemblies are composed of smaller discrete structures (<1 nm) which are likely to be single clusters. The dendritic assemblies for both the Nb3O7and Nb3O6clusters have fractal dimensions of about 1.7 which is very close to that expected for simple diffusion limited aggregation. Annealing the Nb3O7,6/Au(111) surfaces up to 550 K results in changes in assembly sizes and increases in heights, while heating to 700 results in the disruption of the assemblies into smaller structures. By contrast, the as-deposited Nb3O5/Au(111) surface at RT exhibits compact cluster structures which become 3D nanoparticles when annealed above 550 K. Differences in the observed surface structures and thermal stability are attributed to differences in metal-oxygen stoichiometry which can influence cluster binding energies, mobility and inter-cluster interactions.

14.
JAMA Netw Open ; 4(8): e2120040, 2021 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-34369989

RESUMEN

Importance: Leptomeningeal disease (LMD) is a devastating complication of cancer that is frequently underdiagnosed owing to the low sensitivity of cerebrospinal fluid (CSF) cytologic assessment, the current benchmark diagnostic method. Improving diagnostic sensitivity may lead to improved treatment decisions. Objective: To assess whether cell-free DNA (cfDNA) analysis of CSF may be used to diagnose LMD more accurately than cytologic analysis. Design, Setting, and Participants: This diagnostic study conducted in a neuro-oncology clinic at 2 large, tertiary medical centers assessed the use of genomic sequencing of CSF samples obtained from 30 patients with suspected or confirmed LMD from 2015 through 2018 to identify tumor-derived cfDNA. From the same CSF samples, cytologic analyses were conducted, and the results of the 2 tests were compared. This study consisted of 2 patient populations: 22 patients with cytologically confirmed LMD without parenchymal tumors abutting their CSF and 8 patients with parenchymal brain metastases with no evidence of LMD. Patients were considered positive for the presence of LMD if previous CSF cytologic analysis was positive for malignant cells. The analysis was conducted from 2015 to 2018. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of cfDNA analysis, defined as the number of tests that resulted in correct diagnoses out of the total number of tests assayed. Hypotheses were formed before data collection. Results: In total, 30 patients (23 women [77%]; median age, 51 years [range, 28-81 years]), primarily presenting with metastatic solid malignant neoplasms, participated in this study. For 48 follow-up samples from patients previously diagnosed via cytologic analysis as having LMD with no parenchymal tumor abutting CSF, cfDNA findings were accurate in the assessment of LMD in 45 samples (94%; 95% CI, 83%-99%), whereas cytologic analysis was accurate in 36 samples (75%; 95% CI, 60%-86%), a significant difference (P = .02). Of 43 LMD-positive samples, CSF cfDNA analysis was sensitive to LMD in 40 samples (93%; 95% CI, 81%-99%), and cytologic analysis was sensitive to LMD in 31 samples (72%; 95% CI, 56%-85%), a significant difference (P = .02). For 3 patients with parenchymal brain metastases abutting the CSF and no suspicion of LMD, cytologic findings were negative for LMD in all 3 patients, whereas cfDNA findings were positive in all 3 patients. Conclusions and Relevance: This diagnostic study found improved sensitivity and accuracy of cfDNA CSF testing vs cytologic assessment for diagnosing LMD with the exception of parenchymal tumors abutting CSF, suggesting improved ability to diagnosis LMD. Consideration of incorporating CSF cfDNA analysis into clinical care is warranted.

15.
Cell Rep ; 36(5): 109491, 2021 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-34348154

RESUMEN

The exocyst is an evolutionarily conserved protein complex that regulates vesicular trafficking and scaffolds signal transduction. Key upstream components of the exocyst include monomeric RAL GTPases, which help mount cell-autonomous responses to trophic and immunogenic signals. Here, we present a quantitative proteomics-based characterization of dynamic and signal-dependent exocyst protein interactomes. Under viral infection, an Exo84 exocyst subcomplex assembles the immune kinase Protein Kinase R (PKR) together with the Hippo kinase Macrophage Stimulating 1 (MST1). PKR phosphorylates MST1 to activate Hippo signaling and inactivate Yes Associated Protein 1 (YAP1). By contrast, a Sec5 exocyst subcomplex recruits another immune kinase, TANK binding kinase 1 (TBK1), which interacted with and activated mammalian target of rapamycin (mTOR). RALB was necessary and sufficient for induction of Hippo and mTOR signaling through parallel exocyst subcomplex engagement, supporting the cellular response to virus infection and oncogenic signaling. This study highlights RALB-exocyst signaling subcomplexes as mechanisms for the integrated engagement of Hippo and mTOR signaling in cells challenged by viral pathogens or oncogenic signaling.

17.
J Infect Dis ; 2021 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-34282461

RESUMEN

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to five SARS-CoV-2 antigens and the Spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to eleven months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range: 11%, 94%) of anti-Spike IgG remains, 31% (9%, 89%) anti-RBD IgG remains, and 7% (1%, 31%) anti-Nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a sero-prevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection which can be used to reconstruct past epidemics.

18.
EBioMedicine ; 70: 103495, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34304047

RESUMEN

BACKGROUND: Children are underrepresented in the COVID-19 pandemic and often experience milder disease than adolescents and adults. Reduced severity is possibly due to recent and more frequent seasonal human coronaviruses (HCoV) infections. We assessed the seroprevalence of SARS-CoV-2 and seasonal HCoV specific antibodies in a large cohort in north-eastern France. METHODS: In this cross-sectional seroprevalence study, serum samples were collected from children and adults requiring hospital admission for non-COVID-19 between February and August 2020. Antibody responses to SARS-CoV-2 and seasonal HCoV (229E, HKU1, NL63, OC43) were assessed using a bead-based multiplex assay, Luciferase-Linked ImmunoSorbent Assay, and a pseudotype neutralisation assay. FINDINGS: In 2,408 individuals, seroprevalence of SARS-CoV-2-specific antibodies was 7-8% with three different immunoassays. Antibody levels to seasonal HCoV increased substantially up to the age of 10. Antibody responses in SARS-CoV-2 seropositive individuals were lowest in adults 18-30 years. In SARS-CoV-2 seronegative individuals, we observed cross-reactivity between antibodies to the four HCoV and SARS-CoV-2 Spike. In contrast to other antibodies to SARS-CoV-2, specific antibodies to sub-unit 2 of Spike (S2) in seronegative samples were highest in children. Upon infection with SARS-CoV-2, antibody levels to Spike of betacoronavirus OC43 increased across the whole age spectrum. No SARS-CoV-2 seropositive individuals with low levels of antibodies to seasonal HCoV were observed. INTERPRETATION: Our findings underline significant cross-reactivity between antibodies to SARS-CoV-2 and seasonal HCoV, but provide no significant evidence for cross-protective immunity to SARS-CoV-2 infection due to a recent seasonal HCoV infection. In particular, across all age groups we did not observe SARS-CoV-2 infected individuals with low levels of antibodies to seasonal HCoV. FUNDING: This work was supported by the « URGENCE COVID-19 ¼ fundraising campaign of Institut Pasteur, by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID), and by the REACTing (Research & Action Emerging Infectious Diseases), and by the RECOVER project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 101003589, and by a grant from LabEx IBEID (ANR-10-LABX-62-IBEID).


Asunto(s)
COVID-19/inmunología , Inmunidad Humoral/inmunología , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/inmunología , Niño , Preescolar , Ensayos Clínicos como Asunto , Reacciones Cruzadas/inmunología , Estudios Transversales , Femenino , Francia , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Estaciones del Año , Estudios Seroepidemiológicos , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven
19.
Am J Crim Justice ; : 1-18, 2021 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-34248322

RESUMEN

The opioid crisis is the most persistent, long-term public health emergency facing the United States, and available evidence suggests the crisis has worsened during the COVID-19 global pandemic. Naloxone is an effective overdose response that saves lives, but the drug does not address problematic drug use, addiction, or the underlying conditions that lead to overdoses. The opioid crisis is at its core a multidisciplinary, multisystem problem, and an effective response to the crisis requires collaboration across those various systems. This paper describes such a collaborative effort. The Tempe First-Responder Opioid Recovery Project is a multidisciplinary partnership that includes police officers, social workers, substance use peer counselors, public health professionals, police researchers, and drug policy/harm reduction researchers. The project, 10 months underway, trained and equipped Tempe (AZ) police officers to administer Narcan. In addition, a 24/7 in-person "Crisis Outreach Response Team" rapidly responds to any suspected overdose and offers follow-up support, referrals, and services to the individual (and loved ones) for up to 45 days after the overdose. We present preliminary project data including interviews with project managers, counselors, and police officers, descriptions of Narcan administrations in the field, and aggregate data on client service engagement. These data highlight the complexity of the opioid crisis, the collaborative nature of the Tempe project, and the importance of initiating a multidisciplinary, comprehensive response to effectively deal with the opioid problem.

20.
J Surg Oncol ; 2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34310702

RESUMEN

BACKGROUND AND OBJECTIVES: Recent studies suggest that bacteria influence the pathogenesis of primary colorectal cancer (CRC), yet their role in recurrence after resection is largely unknown. We have discovered that collagenase-producing bacteria promote cancer recurrence in mice, and that antibiotic bowel decontamination decreases colonization of these same organisms in humans. We hypothesized that preoperative combined mechanical and oral antibiotic bowel preparation would improve disease-free survival (DFS) in patients undergoing surgery for CRC. METHODS: We reviewed a cancer registry of patients treated for CRC at a tertiary center. Patients who received bowel preparation were compared to those that did not via a 1:1-propensity score matched for follow-up, age, sex, BMI, stage, location, chemoradiation, infection, anastomotic leak, and blood transfusion. RESULTS: One thousand two hundred and seventy-nine patients met inclusion criteria. Following propensity score matching, 264 patients receiving bowel prep were matched to 264 patients who did not. Kaplan-Meier estimates showed that patients who received bowel prep had a significantly improved 5-year DFS compared to those that did not (76.3% vs. 64.2%; p < .01). Cox regression demonstrated that bowel prep was associated with improved DFS (HR, 0.57; 95% CI, 0.37-0.89; p < .01). CONCLUSION: Combined mechanical and oral antibiotic bowel preparation is independently associated with improved recurrence-free survival in patients undergoing surgery for CRC.

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