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1.
Clin Transplant ; 38(1): e15161, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37842872

RESUMO

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.


Assuntos
Hepatite C Crônica , Hepatite C , Transplante de Rim , Humanos , Hepacivirus , Antivirais/uso terapêutico , Transplante de Rim/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Hepatite C/cirurgia , Hepatite C/etiologia , Doadores de Tecidos , Rim
2.
J Org Chem ; 87(22): 15679-15683, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36305839

RESUMO

Heterocyclic sulfones, sulfonamides, and sulfonyl fluorides constitute an important structural motif in medicinal chemistry. Methods to make six-membered heteroaromatic sulfonyl compounds, however, remain challenging, and most efforts rely on commercial sulfonyl chlorides. We report herein the reaction of sodium tert-butyldimethyl silyloxymethylsulfinate with quinoline N-oxides to selectively furnish C2-substituted sulfones. The silyloxymethylsulfinate can be deprotected to then form sulfonyl fluorides, sulfonamides, and sulfones. This transformation is scalable and has broad applicability to a wide array of quinoline and isoquinoline functionality.


Assuntos
Fluoretos , Quinolinas , Sulfonamidas/química , Sulfonas/química , Quinolinas/química
3.
Protein J ; 43(1): 96-114, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38127181

RESUMO

Divergently evolved Tartrate dehydrogenase (TDH) exhibits multiple catalytic activities at a single active site; the enzyme from P. putida (pTDH) being structurally and biochemically well-characterized. Occurrence of TDH-associated ability to aerobically metabolize L-tartrate in Bacillus isolates and limited resemblance of ycsA-encoded protein sequences with pTDH rendered Bacillus TDH as an intriguing enzyme with possible catalytic diversity as well as evolutionary significance. The present study explores substrate interactions of TDHs from B. subtilis 168 (168bTDH) and B. licheniformis DSM-13 (429bTDH) through kinetic, structural and molecular docking-based analysis. Heterologously expressed bTDHs, purified from insoluble fractions of E. coli BL21(DE3) cells, could significantly catalyze L-tartrate and meso-tartrate as substrates in forward reaction. Unlike pTDH, bTDHs distinctly and more efficiently catalyzed the reverse reaction using dihydroxyfumarate substrate following sigmoidal kinetics; the ability being ~ 4 fold higher in 168bTDH. Their binding energies predicted from molecular docking, further substantiated the relative substrate specificities, while revealing major residues involved in protein-ligand interactions at active site. The kinetic analysis and homology modelling validated using Ramachandran Plot analysis predicted a dimeric nature for bTDH. Collectively, the results highlight unique catalytic potential of phylogenetically recent bTDHs, offering an important protein engineering target to mediate efficient enantioselective enzymatic biotransformations.


Assuntos
Oxirredutases do Álcool , Bacillus , Bacillus/enzimologia , Bacillus/genética , Catálise , Escherichia coli/genética , Cinética , Simulação de Acoplamento Molecular , Especificidade por Substrato , Tartaratos
4.
Cureus ; 16(7): e64226, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39130905

RESUMO

Brachial plexus palsy is a complex neuropathy associated with traumatic injuries, inflammatory processes, and tumors. In this report, we present an unusual case of brachial plexus palsy in a 72-year-old man with a history of chronic alcohol abuse. The patient presented to the emergency room with left arm weakness following a fall under the influence of alcohol that resulted in prolonged immobilization. An initial neurologic exam identified paralysis, numbness, and pain in the left upper extremity; however, further studies confirmed the absence of acute fractures or evidence of compartment syndrome. This case highlights the potential for alcohol intoxication and prolonged immobilization, in the absence of traumatic injury, as a contributing cause of brachial plexus palsy. Furthermore, this case emphasizes the importance of considering alternative causes of brachial plexus injury for prompt diagnosis and treatment.

5.
Cureus ; 15(8): e42843, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37664262

RESUMO

Introduction Febrile neutropenia is a commonly encountered medical emergency in patients undergoing cancer treatment and can delay and modify the course of treatment and even lead to dire outcomes, including death. The cause of fever in a post-chemotherapy-induced neutropenic patient can be confusing to treating physicians. A review of the literature demonstrated that blood culture results could determine the cause of febrile neutropenia in only approximately 10% to 25% of patients. The objective of our study was to measure the incidence of positive blood cultures, urine cultures, and other body fluid cultures resulting in chemotherapy-induced neutropenia and further classify fever episodes into three neutropenic fever syndromes, such as microbiologically documented, clinically suspected, or unknown causes of fever, respectively. Methods We conducted a prospective observational study on 399 chemotherapy-induced neutropenic fever episodes with the aim of classifying them into one of the three neutropenic syndromes. We tried to document the cause of the fever in these patients. We also noted the type of cancer treatment regimen they were on and correlated their clinical profile with their body fluid cultures, including blood cultures, urine cultures, and other body fluid cultures. We then categorized each fever episode into one of three neutropenic syndromes. Results We studied 399 febrile neutropenic episodes. We were able to microbiologically document the cause of fever in 39% of the cases, and we obtained growth in 51 out of 399 blood cultures (13%), which was comparable to the available literature, and urine culture showed growth in 62 out of 399 cultures (16%), while other body cultures such as pus culture, bile culture, and bronchioalveolar lavage cultures collectively showed growth in 42 out of 399 episodes (10%). The most common bacteria isolated in both blood and urine cultures were Escherichia coli. Cumulatively, including blood, urine, and body fluid cultures, we were able to classify 39% (155 out of 399 cases) of febrile neutropenic episodes as microbiologically documented. The cause of fever was clinically suspected by means of careful history taking and an extensive physical examination in 31% (125 out of 399) without growth evidence in blood cultures, urine cultures, or any other body fluid culture. The cause of fever remained unknown in 119 cases (30%) of patients and was classified under the unknown cause of fever. Conclusions We conclude by stating that the study of fever in a neutropenic patient should include a thorough history and clinical evaluation of blood, urine, and other body fluid cultures instead of solely relying on blood culture results. We recommend further classifying patients into one of the three neutropenic fever syndromes, such as those that are microbiologically documented, clinically suspected, or unknown. Our blood cultures were able to give us a 13% positivity rate, whereas microbiologically, we were able to isolate an organism likely causing fever in 39% of patients. The cause of fever was suspected clinically in 31% of patients, but we were unsuccessful in microbiologically documenting any culture growth in blood, urine, or any other body fluid culture. The cause of fever remained a mystery and unknown to us without any microbiological or clinical cues in 119 cases (30%) of febrile neutropenic episodes.

6.
JBI Evid Synth ; 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37779423

RESUMO

OBJECTIVE: The objective of the review was to map the similarities and differences in the wound care practices of nurse practitioners, clinical nurse specialists, and advanced practice registered nurses, globally. INTRODUCTION: Advanced practice nurses have graduate education and advanced scope of practice. Adding advanced wound care training to their skillset provides an opportunity for advanced practice nurses to provide wound care. INCLUSION CRITERIA: This review considered for inclusion advanced practice nurses globally who are registered nurses with graduate-level education and advanced training (certification/education) in wound care in any setting. METHODS: The review was conducted using JBI methodology for scoping reviews. The databases searched included MEDLINE, CINAHL, ProQuest Nursing and Allied Health, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus, and ProQuest Dissertations and Theses. To reflect changes in the advanced practice nursing scope of practice, searches were limited to articles published from 2011. Articles in languages other than English were translated. Two reviewers independently reviewed titles and abstracts; relevant sources were retrieved in full and reviewed. An additional independent reviewer resolved any disagreements. Data were extracted using a data extraction tool. Extracted data included similarities and differences in wound care practice (type of wound, practice setting, treatments). RESULTS: There were 2504 abstracts screened, and 158 were screened at full text. Seven articles were included in this review: 3 sources from the United States, 2 from Australia, and 1 each from Canada and The Netherlands. All 7 sources focused on nurse practitioners; wound care education varied from certification in wound ostomy to a master's education in wounds. The practice setting varied; there were 2 primary care clinics; 2 community clinics; 1 wound care center; a suburban hospital, and a study that included tertiary, community, and residential care. Treatments varied, but sources specific to pressure injuries discussed assessments, cleansing, dressings, topical products, and offloading surfaces/equipment, and 1 examined the impact of hiring nurse practitioners as wound care consultants. Sources that discussed treatments for various wounds described comprehensive assessments, diagnostic investigations, referrals, wound management, and medications prescribed. Outcomes included improved healing, decreased incidence, increased patient satisfaction, access to care, and reduced referrals for additional care. CONCLUSIONS: This review outlined the characteristics of advanced practice nurses and their practice settings, types of wounds, and treatments provided. The findings demonstrated positive results with advanced practice nurses providing wound care. Many articles regarding advanced practice nurses with advanced wound care expertise lack the description of the graduate-level education and/or the specifics regarding wound care certification. This prevents comparison of advanced practice nurses with each other and other providers on the impact that advanced practice nurses have on the health care system in relation to wound care, including cost, access to services, and patient satisfaction.

7.
Org Lett ; 24(40): 7394-7399, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36194682

RESUMO

Functionalized pyridine and quinoline rings are important components of numerous bioactive molecules and natural products; however, diversification of these rings often requires de novo heterocycle ring synthesis or demanding reaction conditions. We report a method for desulfinative alkylation of pyridine and quinoline N-methoxide salts that operates under both photocatalytic and electrostatic electron donor-acceptor-mediated pathways. Unlike most EDA-mediated processes, this reaction operates in the absence of light and with the desulfination of the donor compound.

8.
Heart Surg Forum ; 11(3): E188-92, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19176296

RESUMO

OBJECTIVE: Hemodilution is a well-recognized phenomenon of cardiopulmonary bypass (CPB). The degree of hemodilution has attendant risks. As the degree of hemodilution increases, red blood cell transfusions may be necessary, and the risks of blood transfusions are becoming very well recognized. Blood-conservation programs are being developed worldwide to establish strategies to reduce transfusions. Miniaturized extracorporeal circuits (MECs) are associated with less hemodilution than conventional CPB circuits. The use of MECs can be expected to be associated with fewer red blood cell transfusions. METHODS: The first 250 patients who underwent coronary artery bypass grafting, aortic valve replacement, or both with the use of a MEC were compared with 200 consecutive patients who had similar comorbidities and types of surgery but underwent their operations on a conventional bypass circuit. These surgeries were completed between April 2004 and September 2005 under the care of the same surgical team. The minimum acceptable hematocrit on bypass was 22%. Intra- and postoperative transfusion rates were measured and compared. RESULTS: For conventional bypass, the intraoperative transfusion rate was 36.5%, whereas the rate for the MEC was 23.3%. The postoperative transfusion rate was 55% for operations performed with conventional bypass and 26% for the MEC. The overall in-hospital transfusion rate for conventional bypass was 63% and 36% for the MEC. CONCLUSIONS: The data indicate that use of MECs leads to a lower transfusion rate than in surgeries in which conventional CPB is used.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Circulação Extracorpórea/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Circulação Extracorpórea/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia
9.
J Grad Med Educ ; 9(4): 523-526, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28824770

RESUMO

BACKGROUND: Pediatrics fellowship programs typically are small, embedded in divisions, and vary in their approach to education. Program coordination usually falls to division administrators who operate in silos despite common requirements across programs, creating redundancy and inefficiency. OBJECTIVE: We examined the feasibility, acceptability, and impact of a centralized administrative model for pediatrics fellowship support at a large university-based institution. METHODS: In 2014, administrative support for the pediatrics fellowships at the University of California, San Francisco, was restructured from a model with division-level support to a centralized model. In the new model, a team of 6 full-time administrators supports 19 fellowship programs with a total of 80 fellows. The fellowship support team consists of 3 program coordinators, a data coordinator, a human resource coordinator, a team manager, and a faculty advisor. The team meets twice a month to discuss program issues and innovative ideas. Quarterly meetings are held with all coordinators and directors to discuss changes across fellowships and foster further collaboration. We surveyed program directors to examine the acceptability of the model and assessed its impact on finances and turnover. RESULTS: Of 19 eligible fellowship program directors, 15 (79%) completed the survey. The majority indicated that the new administrative model was "better" or "much better" than the prior model. The new model resulted in decreased costs (an estimated $250,000 per year in salary support) and lower staff turnover. CONCLUSIONS: Centralization of fellowship administration is feasible and offers substantial benefits for all stakeholders involved.


Assuntos
Pessoal Administrativo , Bolsas de Estudo/organização & administração , Internato e Residência , Pediatria/organização & administração , Humanos , Organização e Administração , Pediatria/educação , Inquéritos e Questionários
10.
Br J Oral Maxillofac Surg ; 52(8): 693-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25086833

RESUMO

Maxillofacial injuries are unique because of the anatomical complexity of the area and their associated psychological effects. An understanding of the epidemiology of these injuries is important if we are to develop preventive measures, increase the efficiency and delivery of health services, improve the skills of healthcare providers, and better distribute resources. We retrospectively evaluated data on 4455 patients (aged between 3 and 84 years) who presented with maxillofacial injuries to a tertiary referral hospital in Ahmedabad, India, between 1 January 1999 and 31 January 2010. Of these, 18 needed only rest and medication so 4437 were included. Data included patients'characteristics and the cause of injury. Details on the presentation and severity of injury, associated injuries including head injuries, the influence of alcohol and other drugs, treatment, and outcome, were also included. Around one-third were aged between 21and 30 years, and the male to female ratio was 5:1. The main causes of injury were road traffic accidents (n=2347, 53%) and interpersonal violence (n=1041, 23%). Most road traffic accidents involved two-wheeled vehicles. Alcohol was associated with 11% of injuries. A total of 2546 patients (57%) had mandibular fractures. To reduce the number of injuries we need better road safety laws with stringent enforcement, and the public, particularly those between 15 and 45 years of age, must be educated about road safety.


Assuntos
Traumatismos Maxilofaciais/epidemiologia , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Criança , Pré-Escolar , Traumatismos Craniocerebrais/epidemiologia , Ossos Faciais/lesões , Feminino , Seguimentos , Fixação de Fratura/estatística & dados numéricos , Humanos , Incidência , Índia/epidemiologia , Masculino , Fraturas Mandibulares/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Fraturas Cranianas/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Índices de Gravidade do Trauma , Violência/estatística & dados numéricos , Adulto Jovem
11.
Diagn Microbiol Infect Dis ; 79(1): 10-3, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24582581

RESUMO

The performance characteristics of rapid influenza diagnostic tests vary widely. This study evaluated the BD Veritor™ System Flu A+B (Veritor; BD Diagnostics, Sparks, MD, USA), Quidel® Sofia® Influenza A+B FIA (Sofia; Quidel Corp., San Diego, CA, USA), and Alere BinaxNOW® Influenza A&B (Binax; Alere Scarborough, Inc., Scarborough, ME, USA) compared to reverse transcription-polymerase chain reaction (RT-PCR) for detection of influenza viruses in nasal wash specimens from 240 pediatric patients. Positive percent agreements for influenza A and B virus detection were 93.8% and 94.2%, 95.8% and 98.1%, and 79.2% and 80.8% for Veritor, Sofia, and Binax, respectively. The Veritor and Binax tests demonstrated negative percent agreements >97.9% for detection of both influenza viruses, but the negative percent agreement of the Sofia test was 91.1% for influenza A and 70.7% for influenza B virus. Overall, the Veritor and Sofia tests were nearly as sensitive as RT-PCR and considerably more sensitive than Binax for detection of influenza viruses. However, the accuracy of the Sofia test was significantly lower than either Veritor or Binax.


Assuntos
Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/virologia , Kit de Reagentes para Diagnóstico/virologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Humanos , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo , Fluxo de Trabalho
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