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1.
Cancer ; 130(16): 2770-2781, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38798127

RESUMO

BACKGROUND: The objective of this study was to quantify disparities in cancer treatment delivery between minority-serving hospitals (MSHs) and non-MSHs for breast, prostate, nonsmall cell lung, and colon cancers from 2010 to 2019 and to estimate the impact of improving care at MSHs on national disparities. METHODS: Data from the National Cancer Database (2010-2019) identified patients who were eligible for definitive treatments for the specified cancers. Hospitals in the top decile by minority patient proportion were classified as MSHs. Multivariable logistic regression adjusted for patient and hospital characteristics compared the odds of receiving definitive treatment at MSHs versus non-MSHs. A simulation was used to estimate the increase in patients receiving definitive treatment if MSH care matched the levels of non-MSH care. RESULTS: Of 2,927,191 patients from 1330 hospitals, 9.3% were treated at MSHs. MSHs had significant lower odds of delivering definitive therapy across all cancer types (adjusted odds ratio: breast cancer, 0.83; prostate cancer, 0.69; nonsmall cell lung cancer, 0.73; colon cancer, 0.81). No site of care-race interaction was significant for any of the cancers (p > .05). Equalizing treatment rates at MSHs could result in 5719 additional patients receiving definitive treatment over 10 years. CONCLUSIONS: The current findings underscore systemic disparities in definitive cancer treatment delivery between MSHs and non-MSHs for breast, prostate, nonsmall cell lung, and colon cancers. Although targeted improvements at MSHs represent a critical step toward equity, this study highlights the need for integrated, system-wide efforts to address the multifaceted nature of racial and ethnic health disparities. Enhancing care at MSHs could serve as a pivotal strategy in a broader initiative to achieve health care equity for all.


Assuntos
Neoplasias da Mama , Neoplasias do Colo , Disparidades em Assistência à Saúde , Hospitais , Neoplasias Pulmonares , Neoplasias da Próstata , Humanos , Masculino , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Feminino , Neoplasias da Próstata/terapia , Neoplasias da Próstata/etnologia , Neoplasias do Colo/terapia , Neoplasias do Colo/etnologia , Neoplasias da Mama/terapia , Neoplasias da Mama/etnologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/etnologia , Hospitais/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Estados Unidos , Grupos Minoritários/estatística & dados numéricos
2.
J Urol ; 211(3): 436-444, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38100842

RESUMO

PURPOSE: Flank pain associated with stone disease is typically caused by a stone that obstructs urine flow. However, it is plausible that nonobstructing kidney stones may still cause pain. We performed a multicenter, observational trial to evaluate whether treatment of small nonobstructing calyceal stones improves pain and kidney stone-specific health-related quality of life. MATERIALS AND METHODS: Patients aged 18 years or older with nonobstructing renal stone(s) up to 10 mm in longest diameter and moderate to severe pain were recruited. All participants completed 3 questionnaires: the Brief Pain Inventory (BPI), the Patient-Reported Outcomes Measurement Information System pain interference form 6a, and the Wisconsin Stone Quality of Life questionnaire. Thereafter, all participants underwent ureteroscopy for renal stone treatment. All 3 questionnaires were repeated at 2, 6 to 8, and at 12 weeks postprocedure. The primary outcomes were change in preoperative to 12-week postoperative mean BPI score and worst BPI pain score. RESULTS: A total of 43 patients with nonobstructing kidney stones and associated flank pain were recruited. All stones were removed. Preoperatively, BPI scores for mean pain and worst pain were 5.5 and 7.2, respectively which decreased to 1.8 and 2.8 respectively at 12 weeks postoperatively. Wisconsin Stone Quality of Life questionnaire mean score increased from 70.4 to 115.3 at 12 weeks postoperatively. A total of 86% and 69% of patients had at least a 20% and 50% reduction in their mean pain scores, respectively. CONCLUSIONS: This study determined that patients benefit significantly from the removal of calyceal nonobstructing kidney stones for at least 12 weeks with a reduction in pain and an increase in quality of life. Therefore, surgical removal of these stones in this patient population should be offered as a treatment option.


Assuntos
Dor no Flanco , Cálculos Renais , Humanos , Cálculos Renais/complicações , Cálculos Renais/cirurgia , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Ureteroscopia/métodos
3.
Water Sci Technol ; 89(6): 1441-1453, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38557710

RESUMO

Despite facing many challenges, the exploration of using natural forces and mechanisms besides gravity to enhance particle settling has never ceased. A novel particle separator design, which utilizes multiple vortexes to enhance particle settling, was proposed in this study. The basic principle is using the fluid's energy to generate small swirling currents in a specially designed vortex claw generator. These currents bring suspended particles from the rapid and turbulent inflow to relatively quiet water regions, separating them from the main flows and reducing their travel distance to the wall. To verify the new separator design's performance, comparison studies were carried out in the laboratory using physical models. The results showed that the new design had much higher particle capture rates for the same inflow rates and tested particle sizes. Most importantly, it was able to effectively remove small particles, and particle capture rates were much less affected by fluctuations in inflow rates. Since most existing particle separators failed to perform well under large inflow rates, these characteristics make the new design stand out from other separators. Due to its special structure, its treatment capacity can also be easily increased without changing its horizontal separator size.


Assuntos
Tecnologia , Tamanho da Partícula
4.
J Urol ; : 101097JU0000000000004157, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39077952
8.
Adv Neurobiol ; 35: 87-106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38874719

RESUMO

Understanding the relationship between stress and breast cancer development is essential to preventing and alleviating the cancer. Recent research has shed light on the cognitive, physiological, cellular, and molecular underpinnings of how the endorphin pathway and stress pathway affect breast cancer. This chapter consists of two parts. Part 1 will discuss the role of endorphins in breast cancer development. This includes a discussion of three topics: (1) the neurophysiological effect of endorphins on breast tumor growth in vivo, along with further experiments that will deepen our knowledge of how ß-endorphin affects breast cancer; (2) how both the opioid receptor and somatostatin receptor classes alter intracellular signaling in breast cancer cells; and (3) genetic alleles in the opioid signaling pathway that are correlated with increased breast cancer risk. Part 2 will discuss the role of endorphins in recovery from breast cancer. This includes a discussion of three topics: (1) the relationship between breast cancer diagnosis and depression; (2) the effectiveness of cognitive behavioral therapy in reducing stress in breast cancer patients; and (3) the effect of psychotherapy and exercise on preserving telomere length in breast cancer patients.


Assuntos
Neoplasias da Mama , Estresse Psicológico , Animais , Feminino , Humanos , beta-Endorfina/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Terapia Cognitivo-Comportamental , Depressão/metabolismo , Endorfinas/metabolismo , Receptores Opioides/metabolismo , Transdução de Sinais , Estresse Psicológico/metabolismo
9.
J Hosp Med ; 19(7): 581-588, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38462763

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus (PIV) hospitalize many people yearly. Though severe lower respiratory tract disease has been described in children, the elderly, and the immunocompromised, there is a gap in our understanding of RSV, hMPV, and PIV in hospitalized adults. We sought to evaluate the association of RSV, hMPV, and PIV with severe respiratory disease requiring noninvasive or mechanical ventilation and death in hospitalized adults in the United States. METHODS: We conducted a retrospective, pooled, cross-sectional study of general medicine hospitalizations in the United States from 2016 to 2019 using the National Inpatient Sample published by the Agency for Healthcare Quality and Research. We used multivariable Poisson regression to estimate the likelihood of severe respiratory disease or death. We used linear regression to estimate the mean difference in length of stay for those hospitalized with and without a respiratory virus. RESULTS: We found that RSV (incidence rate ratio [IRR]: 1.68, 95% confidence interval [CI]: 1.61-1.74, p < .001), hMPV (IRR: 1.82, 95% CI: 1.71-1.93, p < .001), and PIV (IRR: 1.81, 95% CI: 1.68-1.94, p < .001) were independently associated with severe respiratory disease, even after adjustment. Additionally, we found the presence of a respiratory virus prolonged hospitalizations by (0.79 ± 0.27 days, p < .003) for RSV, (0.88 ± 0.28 days, p < .002) for hMPV, and (1.43 ± 0.30 days, p < .001) for PIV. CONCLUSIONS: RSV, hMPV, and PIV have a significant burden on hospitalized adults, even without classic risk factors.


Assuntos
Hospitalização , Metapneumovirus , Infecções por Paramyxoviridae , Infecções por Vírus Respiratório Sincicial , Humanos , Estados Unidos/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Masculino , Feminino , Estudos Transversais , Estudos Retrospectivos , Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/epidemiologia , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Adulto , Idoso , Vírus Sincicial Respiratório Humano/isolamento & purificação , Tempo de Internação/estatística & dados numéricos
10.
Clin Pharmacol Drug Dev ; 13(4): 367-379, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38315144

RESUMO

Etripamil, a fast-acting nondihydropyridine L-type calcium channel blocker, is under investigation for potential self-administration for the acute treatment of supraventricular tachyarrhythmias in a medically unsupervised setting. We report detailed pharmacokinetics and pharmacodynamics of intranasally administered etripamil in healthy adults from 2 Phase 1, randomized, double-blind studies: Study MSP-2017-1096 (sequential dose-escalation, crossover study design, n = 64) and NODE-102 (single dose, 4-way crossover study, n = 24). Validated bioanalytical assays determined plasma concentrations of etripamil and its inactive metabolite. Noncompartmental pharmacokinetic parameters were calculated. Pharmacodynamic parameters were determined for PR interval, blood pressure, and heart rate. Etripamil was rapidly absorbed intranasally, with time to maximal plasma concentration of 5-8.5 minutes, corresponding to a rapid greater than 10% increase in mean maximum PR interval from baseline within 4-7 minutes of doses of 60 mg or greater. Following peak plasma concentrations, systemic etripamil levels declined rapidly within the first 15 minutes following dosing and decreased more gradually thereafter. PR interval prolongation greater than 10% from baseline was generally sustained for about 45 minutes at doses of 60 mg or greater. The mean terminal half-life ranged from about 1.5 hours with 60 mg to about 2.5-3 hours for the 70- and 105-mg doses. Etripamil was generally well tolerated without symptomatic hypotension. Adverse events were primarily mild to moderate and related to the administration site; no serious adverse events or episodes of atrioventricular block occurred. Intranasal etripamil administration, at doses of 60 mg or greater, produced rapidly occurring slowing of atrioventricular nodal conduction with a limited duration of effect without hemodynamic or electrocardiographic safety signals in healthy volunteers.


Assuntos
Benzoatos , Bloqueadores dos Canais de Cálcio , Adulto , Humanos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Estudos Cross-Over , Administração Intranasal
11.
Plast Reconstr Surg Glob Open ; 12(6): e5888, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855134

RESUMO

Background: Scrubs have become widespread office attire for plastic surgeons. The purpose of this study is to evaluate the public perception of scrub color and style for plastic surgeons. Methods: A crowdsourced survey was performed via MTurk. Respondents were asked to rate images of a surgeon dressed in black, navy, blue, and green scrubs as well as traditional or fitted scrubs. Qualities including representativeness, skill, trustworthiness, knowledge, and compassion were rated on a Likert scale across all images. Analysis of variance and one-sided t test were used to analyze differences in means. Results: In total, 562 responses were collected. For female plastic surgeons, navy and blue scrubs were perceived to be superior to those wearing black for skill, representativeness, trustworthiness, and compassion (P < 0.05). For male plastic surgeons, navy and blue scrubs were superior to black for knowledge, skill, representativeness, trustworthiness, and compassion (P < 0.05). For skill and representativeness, navy was superior to green (P < 0.05). For representativeness, blue was superior to green (P < 0.05). For trustworthiness and compassion, green was superior to black (P < 0.05). Fitted scrubs were significantly preferred (P < 0.05) across all characteristics with the exception of representativeness in the subgroup of male plastic surgeons. Conclusions: Black scrubs are associated with more negative characteristics than navy or blue scrubs, which were found to be the most positively perceived. Fitted scrubs were associated with positive characteristics for both male and female surgeons. The purchase of fitted scrubs may be a worthwhile purchase to maximize the patient-physician relationship.

12.
bioRxiv ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39071446

RESUMO

Peptide-enabled ribonucleoprotein delivery for CRISPR engineering (PERC) is a new approach for ex vivo genome editing of primary human cells. PERC uses a single amphiphilic peptide reagent to mediate intracellular delivery of the same pre-formed CRISPR ribonucleoprotein enzymes that are broadly used in research and therapeutics, resulting in high-efficiency editing of stimulated immune cells and cultured hematopoietic stem and progenitor cells (HSPCs). PERC facilitates nuclease-mediated gene knockout, precise transgene knock-in, and base editing. PERC involves mixing the CRISPR ribonucleoprotein enzyme with peptide and then incubating the formulation with cultured cells. For efficient transgene knock-in, adeno-associated virus (AAV) bearing homology-directed repair template DNA may be included. In contrast to electroporation, PERC is appealing as it requires no dedicated hardware and has less impact on cell phenotype and viability. Due to the gentle nature of PERC, delivery can be performed multiple times without substantial impact to cell health or phenotype. Here we report methods for improved PERC-mediated editing of T cells as well as novel methods for PERC-mediated editing of HSPCs, including knockout and precise knock-in. Editing efficiencies can surpass 90% using either Cas9 or Cas12a in primary T cells or HSPCs. Because PERC calls for only three readily available reagents - protein, RNA, and peptide - and does not require dedicated hardware for any step, PERC demands no special expertise and is exceptionally straightforward to adopt. The inherent compatibility of PERC with established cell engineering pipelines makes this approach appealing for rapid deployment in research and clinical settings.

13.
bioRxiv ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38979175

RESUMO

Natural killer (NK) cells respond rapidly in early HIV-1 infection. HIV-1 prevention and control strategies harnessing NK cells could be enabled by mechanistic understanding of how NK cells recognize HIV-infected T cells. Here, we profiled the phenotype of human primary NK cells responsive to autologous HIV-1-infected CD4 + T cells in vitro. We characterized the patterns of NK cell ligand expression on CD4 + T cells at baseline and after infection with a panel of transmitted/founder HIV-1 strains to identify key receptor-ligand pairings. CRISPR editing of CD4 + T cells to knockout the NKp30 ligand B7-H6, or the NKG2D ligands MICB or ULBP2 reduced NK cell responses to HIV-infected cells in some donors. In contrast, overexpression of NKp30 or NKG2D in NK cells enhanced their targeting of HIV-infected cells. Collectively, we identified receptor-ligand pairs including NKp30:B7-H6 and NKG2D:MICB/ULBP2 that contribute to NK cell recognition of HIV-infected cells.

14.
Adv Mater ; : e2407102, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39081108

RESUMO

Catalysis is crucial for clean energy, green chemistry, and environmental remediation, but traditional methods rely on expensive and scarce precious metals. This review addresses this challenge by highlighting the promise of earth-abundant catalysts and the recent advancements in their rational design. Innovative strategies such as physics-inspired descriptors, high-throughput computational techniques, and artificial intelligence (AI)-assisted design with machine learning (ML) are explored, moving beyond time-consuming trial-and-error approaches. Additionally, biomimicry, inspired by efficient enzymes in nature, offers valuable insights. This review systematically analyses these design strategies, providing a roadmap for developing high-performance catalysts from abundant elements. Clean energy applications (water splitting, fuel cells, batteries) and green chemistry (ammonia synthesis, CO2 reduction) are targeted while delving into the fundamental principles, biomimetic approaches, and current challenges in this field. The way to a more sustainable future is paved by overcoming catalyst scarcity through rational design.

15.
Can Urol Assoc J ; 18(6): 190-193, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38381925

RESUMO

INTRODUCTION: Most robot-assisted surgery (RAS) systems in Canada are donor-funded, with constraints on implementation and access due to significant costs, among other factors. Herein, we evaluated the impact of the growing multispecialty use of RAS on urologic RAS access and outcomes in the past decade. METHODS: We conducted a retrospective review of all RAS performed by different surgical specialties in two high-volume academic hospitals between 2010 and 2019 (prior to the COVID pandemic). The assessed outcomes included the effect of increased robot access over the years on annual robotic-assisted radical prostatectomy (RARP) volumes, surgical waiting times (SWT), and pathologically positive surgical margins (PSM). Data were collected and analyzed from the robotic system and hospital databases. RESULTS: In total, six specialties (urology, gynecology, general, cardiac, thoracic, and otorhinolaryngologic surgery) were included over the study period. RAS access by specialty doubled since 2010 (from three to six). The number of active robotic surgeons tripled from seven surgeons in 2010 to 20 surgeons in 2019. Moreover, there was a significant drop in average case volume, from a peak of 40 cases in 2014 to 25 cases in 2019 (p=0.02). RARP annual case volume followed a similar pattern, reaching a maximum of 166 cases in 2014, then declining to 137 cases in 2019. The mean SWT was substantially increased from 52 days in 2014 to 73 days in 2019; however, PSM rates were not affected by the reduction in surgical volumes (p<0.05). CONCLUSIONS: Over the last decade, RAS access by specialty has increased at two Canadian academic centers due to growing multispecialty use. As there was a fixed, single-robotic system at each of the hospital centers, there was a substantial reduction in the number of RAS performed per surgeon over time, as well as a gradual increase in the SWT. The current low number of available robots and unsustainable funding resources may hinder universal patient access to RAS.

16.
mBio ; 15(6): e0060924, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38742824

RESUMO

Mycobacterium abscessus (Mab) affects patients with immunosuppression or underlying structural lung diseases such as cystic fibrosis (CF). Additionally, Mab poses clinical challenges due to its resistance to multiple antibiotics. Herein, we investigated the synergistic effect of dual ß-lactams [sulopenem and cefuroxime (CXM)] or the combination of sulopenem and CXM with ß-lactamase inhibitors [BLIs-avibactam (AVI) or durlobactam (DUR)]. The sulopenem-CXM combination yielded low minimum inhibitory concentration (MIC) values for 54 clinical Mab isolates and ATCC19977 (MIC50 and MIC90 ≤0.25 µg/mL). Similar synergistic effects were observed in time-kill studies conducted at concentrations achievable in clinical settings. Sulopenem-CXM outperformed monotherapy, yielding ~1.5 Log10 CFU/mL reduction during 10 days. Addition of BLIs enhanced this antibacterial effect, resulting in an additional reduction of CFUs (~3 Log10 for sulopenem-CXM and AVI and ~4 Log10 for sulopenem-DUR). Exploration of the potential mechanisms of the synergy focused on their interactions with L,D-transpeptidases (Ldts; LdtMab1-LdtMab4), penicillin-binding-protein B (PBP B), and D,D-carboxypeptidase (DDC). Acyl complexes, identified via mass spectrometry analysis, demonstrated the binding of sulopenem with LdtMab2-LdtMab4, DDC, and PBP B and CXM with LdtMab2 and PBP B. Molecular docking and mass spectrometry data suggest the formation of a covalent adduct between sulopenem and LdtMab2 after the nucleophilic attack of the cysteine residue at the ß-lactam carbonyl carbon, leading to the cleavage of the ß-lactam ring and the establishment of a thioester bond linking the LdtMab2 with sulopenem. In conclusion, we demonstrated the biochemical basis of the synergy of sulopenem-CXM with or without BLIs. These findings potentially broaden the selection of oral therapeutic agents to combat Mab. IMPORTANCE: Treating infections from Mycobacterium abscessus (Mab), particularly those resistant to common antibiotics like macrolides, is notoriously difficult, akin to a never-ending struggle for healthcare providers. The rate of treatment failure is even higher than that seen with multidrug-resistant tuberculosis. The role of combination ß-lactams in inhibiting L,D-transpeptidation, the major peptidoglycan crosslink reaction in Mab, is an area of intense investigation, and clinicians have utilized this approach in the treatment of macrolide-resistant Mab, with reports showing clinical success. In our study, we found that cefuroxime and sulopenem, when used together, display a significant synergistic effect. If this promising result seen in lab settings, translates well into real-world clinical effectiveness, it could revolutionize current treatment methods. This combination could either replace the need for more complex intravenous medications or serve as a "step down" to an oral medication regimen. Such a shift would be much easier for patients to manage, enhancing their comfort and likelihood of sticking to the treatment plan, which could lead to better outcomes in tackling these tough infections. Our research delved into how these drugs inhibit cell wall synthesis, examined time-kill data and binding studies, and provided a scientific basis for the observed synergy in cell-based assays.


Assuntos
Antibacterianos , Cefuroxima , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Mycobacterium abscessus , Mycobacterium abscessus/efeitos dos fármacos , Antibacterianos/farmacologia , Humanos , Cefuroxima/farmacologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Inibidores de beta-Lactamases/farmacologia , Simulação de Acoplamento Molecular , Proibitinas
17.
Urology ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38648950

RESUMO

OBJECTIVE: To explore factors associated with productivity in urologic practice. Work-relative value units (wRVUs), the basis for Center for Medicare & Medicaid Services (CMS) and private payer reimbursements, commonly serve to estimate physician productivity. Limited data describes which practice factors predict increased wRVU productivity. METHODS: The 2017 and 2018 CMS databases were retrospectively queried for urologic Medicare provider demographics and procedural/service details. Medical school graduation year was used to estimate years in practice and generation (Millennial, Gen X, Baby Boomer, or Post-War). Treated patients' demographics were obtained. Adjusted and unadjusted linear mixed models were performed to predict wRVU production. RESULTS: Included were 6773 Medicare-participating urologists across the United States. Millennials produced 1115 wRVUs per year, while Gen X and Baby Boomers produced significantly more (1997 and 2104, respectively, P <.01). Post-War urologists produced numerically more (1287, P = .88). In adjusted analyses, predictors of Medicare wRVU productivity included female and pelvic medicine and reconstructive surgery (exponentiated beta estimate (ß) 1.46, 95% CI 1.32-1.60), men's health (ß 1.22, 95% CI 1.13-1.32), and oncologic subspecialization (ß 1.08, 95% CI 1.02-1.14), female gender (ß 0.87, 95% CI 0.82-0.92), wRVUs generated from inpatient procedures (ß 1.08, 95% CI 1.06-1.09) and office visits (ß 0.88, 95% CI 0.87-0.89), and the level of education (ß 1.10, 95% CI 1.07-1.14) and percent impoverished patients (ß 0.85, 95% CI 0.83-0.88) in provider's practice zip code. CONCLUSION: Urologic experience, specialization, demographics, practice patterns, and patient demographics are significantly associated with wRVU productivity in Medicare settings. Further work should incorporate quality metrics into wRVUs and ensure patient demographics do not affect reimbursement.

18.
ACS Infect Dis ; 10(5): 1767-1779, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38619138

RESUMO

Peptidoglycan synthesis is an underutilized drug target in Mycobacterium tuberculosis (Mtb). Diazabicyclooctanes (DBOs) are a class of broad-spectrum ß-lactamase inhibitors that also inhibit certain peptidoglycan transpeptidases that are important in mycobacterial cell wall synthesis. We evaluated the DBO durlobactam as an inhibitor of BlaC, the Mtb ß-lactamase, and multiple Mtb peptidoglycan transpeptidases (PonA1, LdtMt1, LdtMt2, LdtMt3, and LdtMt5). Timed electrospray ionization mass spectrometry (ESI-MS) captured acyl-enzyme complexes with BlaC and all transpeptidases except LdtMt5. Inhibition kinetics demonstrated durlobactam was a potent and efficient DBO inhibitor of BlaC (KI app 9.2 ± 0.9 µM, k2/K 5600 ± 560 M-1 s-1) and similar to clavulanate (KI app 3.3 ± 0.6 µM, k2/K 8400 ± 840 M-1 s-1); however, durlobactam had a lower turnover number (tn = kcat/kinact) than clavulanate (1 and 8, respectively). KI app values with durlobactam and clavulanate were similar for peptidoglycan transpeptidases, but ESI-MS captured durlobactam complexes at more time points. Molecular docking and simulation demonstrated several productive interactions of durlobactam in the active sites of BlaC, PonA1, and LdtMt2. Antibiotic susceptibility testing was conducted on 11 Mtb isolates with amoxicillin, ceftriaxone, meropenem, imipenem, clavulanate, and durlobactam. Durlobactam had a minimum inhibitory concentration (MIC) range of 0.5-16 µg/mL, similar to the ranges for meropenem (1-32 µg/mL) and imipenem (0.5-64 µg/mL). In ß-lactam + durlobactam combinations (1:1 mass/volume), MICs were lowered 4- to 64-fold for all isolates except one with meropenem-durlobactam. This work supports further exploration of novel ß-lactamase inhibitors that target BlaC and Mtb peptidoglycan transpeptidases.


Assuntos
Aminoaciltransferases , Antituberculosos , Mycobacterium tuberculosis , Inibidores de beta-Lactamases , beta-Lactamases , Aminoaciltransferases/antagonistas & inibidores , Antituberculosos/farmacologia , Antituberculosos/química , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/química , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/química , beta-Lactamases/metabolismo , beta-Lactamases/química , Cinética , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/enzimologia
19.
Urology ; 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39159759

RESUMO

OBJECTIVE: To investigate the feasibility, safety and efficacy of same day discharge (SDD) after Aquablation specifically in an ambulatory surgery center (ASC). METHODS: A prospective cohort of men with significant BPH underwent Aquablation at a single ASC. Comprehensive preoperative assessments were conducted, including uroflowmetry, IPSS, and PVR. Aquablation was performed as morning cases by a single experienced surgeon. Following the procedure, men were assessed for immediate postoperative outcomes, including pain levels, hematuria, and voiding efficiency. Patients meeting discharge criteria were allowed to return home on the same calendar day. RESULTS: A total of 60 consecutive men with a mean prostate size of 115ml underwent Aquablation, 59 (98%) of whom were discharged the dame day. No transfusions or return to the OR occurred. The procedure demonstrated a significant improvement in urinary flow rates and a substantial reduction in IPSS scores at the 1-month post-operative period. Pain scores were found to be minimal, and the incidence of postoperative complications, including hematuria and urinary retention was low and comparable to previously published outcomes. Despite more meticulous focal cautery, no differences in erectile, ejaculatory or adverse outcomes were observed. CONCLUSIONS: Aquablation for BPH at an ASC appears to be a safe and effective approach. Morning procedures and attentive cautery and streamlined patient pathways seem essential for SDD. Despite electrosurgical hemostasis, ejaculatory, sexual and post-operatively pain were not compromised.

20.
J Endourol ; 38(3): 253-261, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38185840

RESUMO

Background: Several centers have reported their experience with single-port robot-assisted partial nephrectomy (SP-RAPN); however, it is uncertain if utilization of this platform represents an improvement in outcomes compared to multiport robot-assisted partial nephrectomy (MP-RAPN). To evaluate this, we performed a meta-analysis to compare the perioperative, oncological, and functional outcomes between SP-RAPN and MP-RAPN. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 1, 2023. A meta-analysis has been reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and assessing the methodological quality of systematic reviews (AMSTAR) guidelines. The odds ratio (OR) and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 374 retrieved abstracts, 29 underwent full-text review, and 8 studies were included in the final analysis, comprising a total cohort of 1007 cases of RAPN (453 SP-RAPN cases and 554 MP-RAPN cases). Compared to MP-RAPN, the SP-RAPN group had a significantly longer ischemia time (MD = 4.6 minutes, 95% CI 2.8 to 6.3, p < 0.001), less estimated blood loss (MD = -12.4 mL, 95% CI -24.6 to -0.3, p = 0.045), higher blood transfusion rate (OR = 2.97, 95% CI 1.33 to 6.65, p = 0.008), and higher postoperative estimated glomerular filtration rate (eGFR) at 6 months (MD = 4.9 mL/min, 95% CI 0.2 to 9.7, p = 0.04). There was no significant difference in other outcomes between the two approaches, including the intraoperative complication, overall postoperative complication, minor postoperative complication (Clavien-Dindo I - II), major postoperative complication (Clavien-Dindo III-V), conversion to radical nephrectomy, pain score on day #1, pain score on discharge, morphine milligram equivalent usage, hospital stay, positive surgical margins, and postoperative eGFR. Conclusions: SP-RAPN represents an emerging technique using a novel platform. Initial studies have demonstrated that SP-RAPN is a safe and feasible approach to performing partial nephrectomy, although with inferior outcomes for ischemia time and blood transfusion rates. Further studies will be necessary to define the best usage of SP-RAPN within the surgeon's armamentarium.


Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Neoplasias Renais/cirurgia , Resultado do Tratamento , Nefrectomia/métodos , Transfusão de Sangue , Procedimentos Cirúrgicos Robóticos/métodos , Complicações Pós-Operatórias/etiologia , Isquemia , Dor , Estudos Retrospectivos
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