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INTRODUCTION: Failure to rescue (FTR) (avoiding death after complications) has been proposed as a measure of hospital quality. Although surviving complications is important, not all rescues are created equal. Patients also place considerable values on being able to return home after surgery and resume their normal lives. From a systems standpoint, nonhome discharge to skilled nursing and other facilities is the biggest driver of Medicare costs. We wanted to determine whether hospitals' ability to keep patients alive after complications was associated with higher rates of home discharge. We hypothesized that hospitals with higher rescue rates would also be more likely to discharge patients home after surgery. METHODS: We conducted a retrospective cohort study using the nationwide inpatient sample. We included 1,358,041 patients ≥18 y old who had elective major surgery (general, vascular, orthopedic) at 3818 hospitals from 2013 to 2017. We predicted the correlation between a hospital's performance (rank) on FTR and its rank in terms of home discharge rate. RESULTS: The cohort had a median age of 66 y (interquartile range [IQR] 58-73), and 77.9% of patients were Caucasian. Most patients (63.6%) were treated at urban teaching institutions. The surgical case mix included patients having colorectal (146,993 patients; 10.8%), pulmonary (52,334; 3.9%), pancreatic (13,635; 1.0%), hepatic (14,821; 1.1%), gastric (9182; 0.7%), esophageal (4494; 0.3%), peripheral vascular bypass (29,196; 2.2%), abdominal aneurysm repair (14,327; 1.1%), coronary artery bypass (61,976; 4.6%), hip replacement (356,400; 26.2%), and knee replacement (654,857; 48.2%) operations. The overall mortality was 0.3%, the average hospital complication rate was 15.9%, the median hospital rescue rate was 99% (IQR 70%-100%), and the median hospital rate of home discharge was 80% (IQR 74%-85%).There was a small but positive correlation between hospitals' performance on the FTR metric and the likelihood of home discharge after surgery (r = 0.0453; P = 0.006). When considering hospital rates of discharge to home following a postoperative complication, there was a similar correlation between rescue rates and probability of home discharge (r = 0.0963; P < 0.001). However, on sensitivity analysis excluding orthopedic surgery, there was a stronger correlation between rescue rates and home discharge rate (r = 0.4047, P < 0.001). CONCLUSIONS: We found a small correlation between a hospital's ability to rescue patients from complication and that hospital's likelihood of discharging patients home after surgery. When excluding orthopedic operations from the analysis, this correlation strengthened. Our findings suggest that efforts to reduce mortality after complications will likely also help patients return home more frequently after complex surgery. However, more work needs to be done to identify successful programs and other patient and hospital factors that affect both rescue and home discharge.
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Medicare , Alta do Paciente , Humanos , Idoso , Estados Unidos/epidemiologia , Estudos Retrospectivos , Hospitais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Probabilidade , Mortalidade HospitalarRESUMO
INTRODUCTION: Older age and frailty increase the risk of poor recovery after surgery. We hypothesized that general surgery operations performed by supervised chief residents, as opposed to attending physicians, would still be safe for these vulnerable patients. MATERIALS AND METHODS: We used the Veterans Affairs Surgical Quality Improvement Program database to identify 114,525 patients age 65+ y, including 18,030 patients age 80+ y and 47,555 categorized as frail, who had a general surgery procedure from 1999 to 2019 that was performed by an attending physician or by a supervised chief resident. Frailty was defined by a Risk Analysis Index score ≥30. We used inverse probability weighting on the propensity score to compare morbidity and mortality between operations performed by attendings versus chief residents. RESULTS: Patients 65 y and above had a 2.1% increase in postoperative complications when the surgery was performed by a chief resident instead of an attending surgeon (95%CI 1.2%-3.0%, P < 0.0001). A similarly increased risk of complications was seen for patients age ≥80 y old (+2.3%, 95%CI 0.7%-3.9%, P = 0.004) and for frail patients (+2.7%, 95%CI 1.4%-4.0%, P < 0.0001). There were no differences in mortality for patients age 65+ y (+0.2%, 95%CI -0.1%-0.5%, P = 0.2), 80+ y (+0.3%, 95%CI -0.6%-1.1%, P = 0.5), or frail patients (+0.2%, 95%CI -0.5%-0.8%, P = 0.6) when their operations were performed by chief residents. CONCLUSIONS: We found a small increase in morbidity and no difference in mortality when older or frail patients were operated on by chief residents rather than attending surgeons. Our findings suggest that it is reasonable and safe for training programs to allow appropriately supervised chief residents to operate on older or frail patients.
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Fragilidade , Cirurgiões , Humanos , Idoso , Idoso de 80 Anos ou mais , Fragilidade/complicações , Idoso Fragilizado , Complicações Pós-Operatórias/etiologia , Medição de RiscoRESUMO
INTRODUCTION: Understanding how resident participation in surgery affects outcomes is critical for academic surgeons. The purpose of this study was to evaluate if resident participation was associated with adverse outcomes for inguinal hernia repair. METHODS: We used the Veterans Affairs Surgical Quality Improvement Program to look at 61,737 patients aged ≥18 y who had open inguinal hernia repairs from 1998 to 2018. Propensity weighting was used to compare postoperative complications and operative time for patients having surgery performed by an attending alone versus attending with a postgraduate year (PGY) 1, 3, or 5 residents. RESULTS: There were 29,806 hernias (48%) repaired by an attending, 12,024 (19%) by an intern, 9008 (15%) by a PGY-3 resident, and 10,898 (18%) by a PGY-5 resident. After propensity weighting, there was a 0.13% (95% CI -0.11% to 0.38%, P = 0.29) increase in complications with PGY-1 participation compared to cases performed by attendings alone, a 0.3% increase (95% CI 0.01% to 0.59%, P = 0.04) for PGY-3 residents, and a 0.4% increase (95% CI 0.11% to 0.69%, P = 0.007) for PGY-5 residents. There was also an increase in operative time of 26 min (95% CI 25 to 27, P < 0.001) with PGY-1 participation, 19 min (95% CI 18 to 20, P < 0.001) with PGY-3 participation, and 23 min (95% CI 22 to 24, P < 0.001) with PGY-5 participation. CONCLUSIONS: Resident involvement in inguinal hernia surgery was associated with a significant increase in operative time but had a minimal impact on postoperative complications. Although resident participation in hernia surgery is safe, surgical programs should focus on enhancing operative efficiency for residents.
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Hérnia Inguinal , Internato e Residência , Competência Clínica , Hérnia Inguinal/cirurgia , Humanos , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Many studies have identified racial disparities in healthcare, but few have described disparities in the use of anesthesia modalities. We examined racial disparities in the use of local versus general anesthesia for inguinal hernia repair. We hypothesized that African American and Hispanic patients would be less likely than Caucasians to receive local anesthesia for inguinal hernia repair. MATERIALS AND METHODS: We included 78,766 patients aged ≥ 18 years in the Veterans Affairs Surgical Quality Improvement Program database who underwent elective, unilateral, open inguinal hernia repair under general or local anesthesia from 1998-2018. We used multiple logistic regression to compare use of local versus general anesthesia and 30-day postoperative complications by race/ethnicity. RESULTS: In total, 17,892 (23%) patients received local anesthesia. Caucasian patients more frequently received local anesthesia (15,009; 24%), compared to African Americans (2353; 17%) and Hispanics (530; 19%), P < 0.05. After adjusting for covariates, we found that African Americans (OR 0.82, 95% CI 0.77-0.86) and Hispanics (OR 0.77, 95% CI 0.69-0.87) were significantly less likely to have hernia surgery under local anesthesia compared to Caucasians. Additionally, local anesthesia was associated with fewer postoperative complications for African American patients (OR 0.46, 95% CI 0.27-0.77). CONCLUSIONS: Although local anesthesia was associated with enhanced recovery for African American patients, they were less likely to have inguinal hernias repaired under local than Caucasians. Addressing this disparity requires a better understanding of how surgeons, anesthesiologists, and patient-related factors may affect the choice of anesthesia modality for hernia repair.
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Anestesia Local/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Herniorrafia/estatística & dados numéricos , Complicações Pós-Operatórias/etnologia , Idoso , Feminino , Hérnia Inguinal/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Veteranos/estatística & dados numéricosRESUMO
Dogs with sinonasal tumors with cribriform plate lysis (modified Adams' stage 4) treated with non-conformal definitive radiotherapy (RT) have short median survivals of 6-7 months. Intensity-modulated radiotherapy with its greater conformality and tumor dose homogeneity may result in more favorable outcomes. Dogs with epithelial or mesenchymal sinonasal tumors and CT evidence of cribriform lysis that received 10 daily fractions of 4.2 Gray using IMRT by helical tomotherapy were included in this single-institution retrospective case series study. Dogs with distant metastasis, previous treatment, or concurrent chemotherapy were excluded. Based on CT, tumors were divided into two groups: cribriform plate lysis only (stage 4a) or intracranial extension (stage 4b). Twenty-nine dogs were included, 23 with carcinoma and six with sarcoma. Eight dogs had stage 4b tumors; two presented with neurologic signs. Two dogs had lymph node metastasis at diagnosis, one confirmed and one suspected. Radiation dose distributions were standardized and patient positioning for RT was verified daily using on-board megavoltage CT. All evaluable dogs had improvement of clinical signs. Median progression free survival was 177 days (95% CI, 128-294 days). Median overall survival was 319 days (95% CI, 188-499 days). Radiotherapy was well tolerated. The most common side effect was grade 1 or 2 oral mucositis. Two dogs that received additional treatment at progression (stereotactic RT [1]; surgery [1]) developed significant late effects. Image-guided definitive-intent IMRT may improve survival in dogs with modified Adams' stage 4 sinonasal tumors and is associated with low morbidity. Intracranial tumor extension was not prognostic in this cohort of uniformly treated dogs.
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Doenças do Cão/radioterapia , Neoplasias Nasais/veterinária , Seios Paranasais , Sarcoma/veterinária , Animais , Intervalo Livre de Doença , Doenças do Cão/mortalidade , Cães , Feminino , Metástase Linfática , Masculino , Neoplasias Nasais/patologia , Neoplasias Nasais/radioterapia , Planejamento da Radioterapia Assistida por Computador/veterinária , Radioterapia de Intensidade Modulada/veterinária , Registros/veterinária , Estudos Retrospectivos , Sarcoma/radioterapia , Sarcoma/secundárioRESUMO
BACKGROUND: Veterans with primary hyperparathyroidism are under diagnosed and undertreated. We report the results of a pilot study to address this problem. METHODS: We implemented a stakeholder-driven, multi-component intervention to increase rates of diagnosis and treatment for primary hyperparathyroidism at a single VA hospital. Intervention effects were evaluated using an interrupted time series analysis. RESULTS: The mean age of Veterans affected by the intervention was 67 years (SD 12.1) and 84 â% were men. Compared to the pre-intervention period, the intervention doubled the proportion of Veterans who were appropriately evaluated for hyperparathyroidism (absolute difference 25 â%, 95 â% CI 11 â%-38 â%, p â< â0.001) and increased referrals for treatment by 27 â% (95 â% CI 7 â%-47 â%, p â< â0.012). CONCLUSION: Our pilot study suggests it is feasible to address the underdiagnosis and undertreatment of primary hyperparathyroidism among Veterans.
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Hiperparatireoidismo Primário , Humanos , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/terapia , Hiperparatireoidismo Primário/complicações , Masculino , Feminino , Idoso , Projetos Piloto , Pessoa de Meia-Idade , Paratireoidectomia/estatística & dados numéricos , Hospitais de Veteranos/estatística & dados numéricos , Veteranos/estatística & dados numéricos , Estados Unidos/epidemiologia , Análise de Séries Temporais Interrompida , Encaminhamento e Consulta/estatística & dados numéricosRESUMO
Importance: Although the incidence of acute appendicitis among adults 65 years and older is high, these patients are underrepresented in randomized clinical trials comparing nonoperative vs operative management of appendicitis; it is unclear whether current trial data can be used to guide treatment in older adults. Objective: To compare outcomes following nonoperative vs operative management of appendicitis in older adults and assess whether they differ from results in younger patients. Design, Setting, and Participants: This retrospective cohort study used US hospital admissions data from the Agency for Healthcare Research and Quality's National Inpatient Sample from 2004 to 2017. Of 723â¯889 adult patients with acute uncomplicated appendicitis, 474â¯845 with known procedure date who survived 24 hours postprocedure and did not have inflammatory bowel disease were included (43â¯846 who were treated nonoperatively and 430â¯999 with appendectomy) were included. Data were analyzed from October 2021 to April 2022. Exposures: Nonoperative vs operative management. Main Outcomes and Measures: The primary outcome was incidence of posttreatment complications. Secondary outcomes included mortality, length of stay, and inpatient costs. Differences were estimated using inverse probability weighting of the propensity score with sensitivity analysis to quantify effects of unmeasured confounding. Results: The median (IQR) age in the overall cohort was 39 (27-54) years, and 29â¯948 participants (51.3%) were female. In patients 65 years and older, nonoperative management was associated with a 3.72% decrease in risk of complications (95% CI, 2.99-4.46) and a 1.82% increase in mortality (95% CI, 1.49-2.15) along with increased length of hospitalization and costs. Outcomes in patients younger than 65 years were significantly different than in older adults, with only minor differences between nonoperative and operative management with respect to morbidity and mortality, and smaller differences in length of hospitalization and costs. Morbidity and mortality results were somewhat sensitive to bias from unmeasured confounding. Conclusions and Relevance: Nonoperative management was associated with reduced complications in older but not younger patients; however, operative management was associated with reduced mortality, hospital length of stay, and overall costs across all age groups. The different outcomes of nonoperative vs operative management of appendicitis in older and younger adults highlights the need for a randomized clinical trial to determine the best approach for managing appendicitis in older patients.
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Apendicite , Humanos , Feminino , Idoso , Adulto , Pessoa de Meia-Idade , Masculino , Apendicite/cirurgia , Apendicite/tratamento farmacológico , Resultado do Tratamento , Estudos Retrospectivos , Apendicectomia/métodos , IncidênciaRESUMO
BACKGROUND: Comparisons of lobectomy versus total thyroidectomy for papillary thyroid cancer have not addressed significant threats to valid inference from observational data. The purpose of this study was to compare survival after lobectomy versus total thyroidectomy for papillary thyroid cancer while addressing bias from unmeasured confounding. METHODS: This retrospective cohort study included 84,300 patients treated with lobectomy or total thyroidectomy for papillary thyroid cancer in the National Cancer Database from 2004 to 2017. The primary outcome was overall survival evaluated by flexible parametric survival models and inverse probability weighting on the propensity score. Bias from unobserved confounding was assessed using two-way deterministic sensitivity analysis and 2-stage least squares regression. RESULTS: The median age of treated patients was 48 years (interquartile range, 37-59), 78% were women, and 76% were white. We found no statistically significant differences in overall survival or 5- and 10-year survival between patients treated with lobectomy or total thyroidectomy. Additionally, we found no statistically significant difference in survival by subgroups, including tumor size (<4 cm or ≥4 cm), age (<65 or ≥65), or estimated risk of mortality. Sensitivity analyses suggested that an unmeasured confounder would need to have an extremely large effect to change the primary finding. CONCLUSION: This is the first study to compare lobectomy and total thyroidectomy outcomes while adjusting for and quantifying the potential effects of unmeasured confounding variables on observational data. The findings suggest that total thyroidectomy is unlikely to offer a survival advantage over lobectomy regardless of tumor size, patient age, or overall risk of death.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Carcinoma Papilar/patologia , Tireoidectomia , Recidiva Local de Neoplasia/cirurgiaRESUMO
Burn patients are particularly susceptible to atypical and opportunistic infections. Here we report an unusual case of a 40-year-old previously healthy man with a 74% TBSA burn injury who developed a presumed Fusarium brain abscess. This patient had a complicated infectious course including ESBL E. coli and Elizabethkingia bacteremia and pneumonia, MRSA ventilator-associated pneumonia, Mycobacterium abscessus bacteremia, and Fusarium fungemia. After diagnosis with a fungal abscess on magnetic resonance imaging of the brain, the patient was treated with aspiration and appropriate antifungal therapies. The patient was eventually transitioned to comfort care and died on hospital day 167. This is the first published report of a Fusarium-related brain abscess since it was first reported in a case report of a burned child in 1974.
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Bacteriemia , Abscesso Encefálico , Queimaduras , Fusarium , Masculino , Criança , Humanos , Adulto , Escherichia coli , Queimaduras/complicações , Queimaduras/terapia , Queimaduras/microbiologia , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/tratamento farmacológico , Abscesso Encefálico/etiologiaRESUMO
Importance: Advocates of laparoscopic surgery argue that all inguinal hernias, including initial and unilateral ones, should be repaired laparoscopically. Prior work suggests outcomes of open repair are improved by using local rather than general anesthesia, but no prior studies have compared laparoscopic surgery with open repair under local anesthesia. Objective: To evaluate postoperative outcomes of open inguinal hernia repair under general or local anesthesia compared with laparoscopic repair. Design, Setting, and Participants: This retrospective cohort study identified 107â¯073 patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent unilateral initial inguinal hernia repair from 1998 to 2019. Data were analyzed from October 2021 to March 2022. Exposures: Patients were divided into 3 groups for comparison: (1) open repair with local anesthesia (n = 22â¯333), (2) open repair with general anesthesia (n = 75â¯104), and (3) laparoscopic repair with general anesthesia (n = 9636). Main Outcomes and Measures: Operative time and postoperative morbidity were compared using quantile regression and inverse probability propensity weighting. A 2-stage least-squares regression and probabilistic sensitivity analysis was used to quantify and address bias from unmeasured confounding in this observational study. Results: Of 107â¯073 included patients, 106â¯529 (99.5%) were men, and the median (IQR) age was 63 (55-71) years. Compared with open repair with general anesthesia, laparoscopic repair was associated with a nonsignificant 0.15% (95% CI, -0.39 to 0.09; P = .22) reduction in postoperative complications. There was no significant difference in complications between laparoscopic surgery and open repair with local anesthesia (-0.05%; 95% CI, -0.34 to 0.28; P = .70). Operative time was similar for the laparoscopic and open general anesthesia groups (4.31 minutes; 95% CI, 0.45-8.57; P = .048), but operative times were significantly longer for laparoscopic compared with open repair under local anesthesia (10.42 minutes; 95% CI, 5.80-15.05; P < .001). Sensitivity analysis and 2-stage least-squares regression demonstrated that these findings were robust to bias from unmeasured confounding. Conclusions and Relevance: In this study, laparoscopic and open repair with local anesthesia were reasonable options for patients with initial unilateral inguinal hernias, and the decision should be made considering both patient and surgeon factors.
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Hérnia Inguinal , Laparoscopia , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Hérnia Inguinal/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Anestesia Geral , HerniorrafiaRESUMO
OBJECTIVE: The COVID-19 pandemic rapidly altered the landscape of medical education, particularly disrupting the residency application process and highlighting the need for structured mentorship programs. This prompted our institution to develop a virtual mentoring program to provide tailored, one-on-one mentoring to medical students applying to general surgery residency. The aim of this study was to examine general surgery applicant perception of a pilot virtual mentoring curriculum. DESIGN: The mentorship program included student-tailored mentoring and advising in 5 domains: resume editing, personal statement composition, requesting letters of recommendation, interview skills, and residency program ranking. Electronic surveys were administered following ERAS application submission to participating applicants. The surveys were distributed and collected via a REDCap database. RESULTS: Eighteen out of 19 participants completed the survey. Confidence in a competitive resume (pâ¯=â¯0.006), interview skills (p < 0.001), obtaining letters of recommendation (pâ¯=â¯0.002), personal statement drafting (p < 0.001), and ranking residency programs (p < 0.001) were all significantly improved following completion of the program. Overall utility of the curriculum and likelihood to participate again and recommend the program to others was rated a median 5/5 on the Likert scale (5 [IQR 4-5]). Confidence in the matching carried a premedian 66.5 (50-65) and a postmedian 84 (75-91) (pâ¯=â¯0.004). CONCLUSION: Following the completion of the virtual mentoring program, participants were found to be more confident in all 5 targeted domains. In addition, they were more confident in their overall ability to match. General Surgery applicants find tailored virtual mentoring programs to be a useful tool allowing for continued program development and expansion.
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COVID-19 , Cirurgia Geral , Internato e Residência , Tutoria , Estudantes de Medicina , Humanos , Mentores , Pandemias , COVID-19/epidemiologia , Cirurgia Geral/educaçãoRESUMO
BACKGROUND: Laparoscopic appendectomy is one of the most common emergency general surgery procedures in the United States. Little is known about its postoperative outcomes for older adults because appendicitis typically occurs in younger patients. The purpose of this study was to examine the association between age and postoperative complications after appendectomy. We hypothesized that age would have a significant and nonlinear association with morbidity. METHODS: We conducted a retrospective cohort study of individuals whose laparoscopic appendectomies were recorded in the Veterans Affairs (VA) Surgical Quality Improvement Program (from 2000-2018; n = 14,619) and National Surgical Quality Improvement Program (2005-2019; n = 349,909) databases. The primary outcome was 30-day morbidity. We used logistic regression with fractional polynomials to model nonlinear relationships between age and outcomes. RESULTS: The median age (interquartile range) of the nonveteran cohort was 36 years (26-51; 8.4% of patients were 65 or older) versus 51 years among veterans (35-63; 21% were 65 or older). For veterans and nonveterans, there was a significant and nonlinear relationship between age and risk of complications. In the nonveteran cohort, the predicted probability (with 95% confidence interval) of postoperative complications was 9.8% (9.7-10.1) at age 65, 11.9% (11.7-12.3) at age 75, and 14.5% (14.1-14.9) at age 85. Among veterans, the risk was 7.5% (6.9-8.1) at age 65, 8.3% (7.6-9.1) at age 75, and 9.1% (8.1-10.1) at age 85. CONCLUSION: For both veterans and nonveterans, older age was associated with a significantly increased risk of postoperative complications. Notably, morbidity within the VA was lower for older adults than in non-VA hospitals.
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Apendicite , Laparoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apendicectomia/efeitos adversos , Apendicectomia/métodos , Apendicite/complicações , Apendicite/cirurgia , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Morbidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Although tick-borne diseases are important causes of morbidity and mortality in dogs in tropical areas, there is little information on the agents causing these infections in the Caribbean. METHODOLOGY: We used PCRs to test blood from a cross-section of dogs on St Kitts for Ehrlichia (E.) canis, Babesia (B.) spp., Anaplasma (A.) spp. and Hepatozoon (H.) spp. Antibodies against E. canis and A. phagocytophilum/platys were detected using commercial immunochromatography tests. Records of the dogs were examined retrospectively to obtain clinical and laboratory data. PRINCIPAL FINDINGS: There was serological and/or PCR evidence of infections of dogs with E. canis (27%; 46/170), Babesia spp. (24%; 90/372) including B. canis vogeli (12%; 43/372) and B. gibsoni (10%; 36/372), A. platys (11%; 17/157) and H. canis (6%; 15/266). We could not identify the Babesia sp. detected in nine dogs. There was evidence of multiple infections with dual infections with E. canis and B. canis vogeli (8%; 14/179) or B. gibsoni (7%; 11/170) being the most common. There was agreement between immunochromatography and PCR test results for E. canis for 87% of dogs. Only 13% of exposed dogs had signs of a tick-borne disease and 38% had laboratory abnormalities. All 10 dogs presenting for a recheck after treatment of E. canis with doxycycline were apparently healthy although all remained seropositive and six still had laboratory abnormalities despite an average of two treatments with the most recent being around 12 months previously. Infections with Babesia spp. were also mainly subclinical with only 6% (4/67) showing clinical signs and 13% (9/67) having laboratory abnormalities. Similarly, animals with evidence of infections with A. platys and H. canis were largely apparently healthy with only occasional laboratory abnormalities. CONCLUSIONS: Dogs are commonly infected with tick-borne pathogens in the Caribbean with most having no clinical signs or laboratory abnormalities.
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Anaplasmose , Babesiose/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Ehrlichiose/veterinária , Doenças Transmitidas por Carrapatos/veterinária , Anaplasma/genética , Anaplasma/imunologia , Animais , Babesia/genética , Babesia/imunologia , Cromatografia de Afinidade , Cães , Reação em Cadeia da Polimerase , Prevalência , Índias Ocidentais/epidemiologiaRESUMO
beta-globin mRNA bearing a nonsense codon is degraded in the cytoplasm of erythroid cells by endonuclease cleavage, preferentially at UG dinucleotides. An endonuclease activity in polysomes of MEL cells cleaved beta-globin and albumin mRNA in vitro at many of the same sites as PMR1, an mRNA endonuclease purified from Xenopus liver. Stable transfection of MEL cells expressing normal human beta-globin mRNA with a plasmid vector expressing the catalytically active form of PMR1 reduced the half-life of beta-globin mRNA from 12 to 1-2 h without altering GAPDH mRNA decay. The reduced stability of beta-globin mRNA in these cells was accompanied by an increase in the production of mRNA decay products corresponding to those seen in the degradation of nonsense-containing beta-globin mRNA. Therefore, beta-globin mRNA is cleaved in vivo by an endonuclease with properties similar to PMR1. Inhibiting translation with cycloheximide stabilized nonsense-containing beta-globin mRNA, resulting in a fivefold increase in its steady-state level. Taken together, our results indicate that the surveillance of nonsense-containing beta-globin mRNA in erythroid cells is a cytoplasmic process that functions on translating mRNA, and endonucleolytic cleavage constitutes one step in the process of beta-globin mRNA decay.
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Códon sem Sentido , Endorribonucleases/metabolismo , Globinas/genética , RNA Mensageiro/metabolismo , Animais , Cicloeximida/farmacologia , Células Precursoras Eritroides/metabolismo , Humanos , Inibidores da Síntese de Proteínas/farmacologia , RNA Mensageiro/efeitos dos fármacos , XenopusRESUMO
Previous work showed that human beta-globin mRNAs harboring a premature termination codon are degraded in the erythroid tissues of mice to products that lack sequences from the mRNA 5' end but contain a 5' cap-like structure. Whether these decay products are the consequence of endonucleolytic or 5'-to-3' exonucleolytic activity is unclear. We report that this beta-globin mRNA decay pathway is recapitulated in cultured mouse erythroleukemia (MEL) cells and targets nonsense-free mRNA to a lesser extent than nonsense-containing mRNA. S1 nuclease mapping and primer extension demonstrated that 70-80% of decay product 5' ends contain a UG dinucleotide. Detection of upstream counterparts of these decay products indicates that they are generated by endonucleolytic activity. Both crude and partially purified polysome extracts prepared from MEL cells contain an endonucleolytic activity that generates decay products comparable to those observed in vivo. These data suggest that an endonuclease with preference for UG dinucleotides is involved in the degradation of nonsense-containing and, to a lesser extent, nonsense-free human beta-globin mRNAs in mouse erythroid cells.