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BACKGROUND: Liver transplantation is considered the definitive treatment for people with liver failure. As part of post-liver transplantation management, immunosuppression (suppressing the host immunity) is given to prevent graft rejections. Immunosuppressive drugs can be classified into those that are used for a short period during the beginning phase of immunosuppression (induction immunosuppression) and those that are used over the entire lifetime of the individual (maintenance immunosuppression), because it is widely believed that graft rejections are more common during the first few months after liver transplantation. Some drugs such as glucocorticosteroids may be used for both induction and maintenance immunosuppression because of their multiple modalities of action. There is considerable uncertainty as to whether induction immunosuppression is necessary and if so, the relative efficacy of different immunosuppressive agents. OBJECTIVES: To assess the comparative benefits and harms of different induction immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different induction immunosuppressive regimens according to their safety and efficacy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until July 2019 to identify randomised clinical trials in adults undergoing liver transplantation. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults undergoing liver transplantation. We excluded randomised clinical trials in which participants had multivisceral transplantation and those who already had graft rejections. DATA COLLECTION AND ANALYSIS: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, and hazard ratio (HR) with 95% credible intervals (CrIs) based on an available case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS: We included a total of 25 trials (3271 participants; 8 treatments) in the review. Twenty-three trials (3017 participants) were included in one or more outcomes in the review. The trials that provided the information included people undergoing primary liver transplantation for various indications and excluded those with HIV and those with renal impairment. The follow-up in the trials ranged from three to 76 months, with a median follow-up of 12 months among trials. All except one trial were at high risk of bias, and the overall certainty of evidence was very low. Overall, approximately 7.4% of people who received the standard regimen of glucocorticosteroid induction died and 12.2% developed graft failure. All-cause mortality and graft failure was lower with basiliximab compared with glucocorticosteroid induction: all-cause mortality (HR 0.53, 95% CrI 0.31 to 0.93; network estimate, based on 2 direct comparison trials (131 participants; low-certainty evidence)); and graft failure (HR 0.44, 95% CrI 0.28 to 0.70; direct estimate, based on 1 trial (47 participants; low-certainty evidence)). There was no evidence of differences in all-cause mortality and graft failure between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). There was also no evidence of differences in serious adverse events (proportion), serious adverse events (number), renal failure, any adverse events (proportion), any adverse events (number), liver retransplantation, graft rejections (any), or graft rejections (requiring treatment) between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the studies reported health-related quality of life. FUNDING: the source of funding for 14 trials was drug companies who would benefit from the results of the study; two trials were funded by neutral organisations who have no vested interests in the results of the study; and the source of funding for the remaining nine trials was unclear. AUTHORS' CONCLUSIONS: Based on low-certainty evidence, basiliximab induction may decrease mortality and graft failure compared to glucocorticosteroids induction in people undergoing liver transplantation. However, there is considerable uncertainty about this finding because this information is based on small trials at high risk of bias. The evidence is uncertain about the effects of different induction immunosuppressants on other clinical outcomes, including graft rejections. Future randomised clinical trials should be adequately powered, employ blinding, avoid post-randomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, graft failure, and health-related quality of life.
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Imunossupressores/administração & dosagem , Transplante de Fígado , Imunologia de Transplantes , Teorema de Bayes , Humanos , Terapia de Imunossupressão/métodos , Metanálise em Rede , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with high metastatic potential. Sentinel lymph node biopsy (SLNB) is used to assess locoregional spread, facilitate staging, and inform prognosis. Positive nodal status is associated with higher recurrence rates and reduced overall survival. Methods: A systematic search was conducted. Eligible articles included patients diagnosed with MCC, who would be candidates for or who had SLNB. The Covidence tool was used for screening and data extraction, including additional treatments, disease-free survival, overall survival, and recurrence. Methodological quality was assessed using the Newcastle-Ottowa Scale criteria. Results: SLNB was associated with increased likelihood of completion lymphadenectomy (223 versus 41), regional radiotherapy (2167 versus 808), and systemic chemotherapy (138 versus 31). Overall survival for patients undergoing SLNB was 81% at 2 years, 75% at 3 years, and 72% at 5 years (odds ratio: 0.79). Hazard ratio for positive SLNB versus negative was 3.36 (P < 0.001). Five-year disease recurrence was 23.3% in patients undergoing SLNB. Conclusions: Lymph node metastases are associated with reduced overall survival and increased recurrence of MCC. Determining nodal status early can inform prognosis, facilitate staging, and determine need for adjuvant treatment. Adjuvant treatments are associated with reduced mortality and improved overall survival; SLNB is an important influencer of their use. Early prophylactic intervention should be considered in MCC in both positive and negative nodal status to improve overall outcomes. Widespread use of SLNB will allow more accurate assessment of the role of nodal status on adjuvant treatment and long-term outcomes.
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Binaries containing a compact object orbiting a supermassive black hole are thought to be precursors of gravitational wave events, but their identification has been extremely challenging. Here, we report quasi-periodic variability in x-ray absorption, which we interpret as quasi-periodic outflows (QPOuts) from a previously low-luminosity active galactic nucleus after an outburst, likely caused by a stellar tidal disruption. We rule out several models based on observed properties and instead show using general relativistic magnetohydrodynamic simulations that QPOuts, separated by roughly 8.3 days, can be explained with an intermediate-mass black hole secondary on a mildly eccentric orbit at a mean distance of about 100 gravitational radii from the primary. Our work suggests that QPOuts could be a new way to identify intermediate/extreme-mass ratio binary candidates.
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On March 22, 2020, the World Health Organization (WHO) pro- claimed the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2 or Covid-19), and the virus has had global impact, with sig- nificant mortality rates observed in high-income countries (HICs) in Europe and the United States (USA). Numerous low- and middle-income countries (LMICs) have signifi- cant unmet healthcare demands, and citizens frequently experience the negative repercussions of their inadequate health care systems. Nigeria, the most populous nation in Africa with an estimated 200 million inhabitants, is not an exception. With the lessons from the 2014 Ebola pandemic in West African states still vivid, procedures such as temperature checks at international airports and medical and travel history questionnaires were swiftly implemented begin- ning in early February 2020.
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Background: The repair of zone 1 flexor tendon injury often relies on re-inserting the flexor digitorum profundus (FDP) tendon to the distal phalanx. The aim of this retrospective study is to compare outcomes at 12 weeks following traditional button-over-nail (BON) versus bone anchor (BA) repair of zone I FDP injury. Methods: Patients undergoing zone 1 FDP repair between April 2007 and September 2018 using a BON or a BA were included in the study. Patient demographics, complications, arc of flexion of distal (distal interphalangeal joint [DIPJ]) and proximal interphalangeal joint (PIPJ) and patient-rated outcomes were analysed. Results: Forty-three patients were included in the study: 21 in the BA group and 22 in the BON group. Good function was achieved by 20 patients in BA versus nine in BON. Complications occurred in five BA patients versus 10 BON patients. Patients achieved a mean active DIPJ flexion of 49° and 31° and PIPJ flexion of 92° and 57° in the BA and BON groups, respectively. Conclusion: Our study demonstrates better arc of motion, patient-rated outcomes and lower complications at 12 weeks after surgery in patients undergoing zone 1 FDP repair using a BA. Level of Evidence: Level III (Therapeutic).
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Traumatismos dos Dedos , Traumatismos dos Tendões , Traumatismos dos Dedos/cirurgia , Humanos , Estudos Retrospectivos , Âncoras de Sutura , Traumatismos dos Tendões/cirurgia , Tendões/cirurgiaRESUMO
We present the case of a 53-year-old woman with silicone breast implants who underwent excision of an abdominal melanoma and sentinel lymph node biopsy. Two lymph nodes were excised; both lying in the breast parenchyma adjacent to the intact right breast capsule. The lymph node histology revealed a subcapsular melanoma deposit along with silicone lymphadenopathy in the sentinel node. This case highlights that sentinel lymph nodes can be located in alternative locations to the common lymphatic basins and, therefore, the importance of preoperative lymphoscintigraphy. We also discuss subclinical breast implant rupture as a causative factor for silicone lymphadenopathy.
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Melanoma , Neoplasias Cutâneas , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Melanoma/cirurgia , Pessoa de Meia-Idade , Micrometástase de Neoplasia , Biópsia de Linfonodo Sentinela , Silicones , Neoplasias Cutâneas/cirurgiaRESUMO
Background Trauma-related injury causes higher mortality than a combination of prevalent infectious diseases. Mortality secondary to trauma is higher in low- and middle-income countries (LMICs) than high-income countries. This review outlines common issues, and potential solutions for those issues, identified in trauma care in LMICs that contribute to poorer outcomes. Methods A literature search was performed on PubMed and Google Scholar using the search terms "trauma," "injuries," and "developing countries." Articles conducted in a trauma setting in low-income countries (according to the World Bank classification) that discussed problems with management of trauma or consolidated treatment and educational solutions regarding trauma care were included. Results Forty-five studies were included. The problem areas broadly identified with trauma care in LMICs were infrastructure, education, and operational measures. We provided some solutions to these areas including algorithm-driven patient management and use of technology that can be adopted in LMICs. Conclusion Sustainable methods for the provision of trauma care are essential in LMICs. Improvements in infrastructure and education and training would produce a more robust health care system and likely a reduction in mortality in trauma-related injuries.
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OBJECTIVE: The aim of this study was to evaluate the impact of redeployment of surgical trainees to intensive care units (ICUs) during the COVID-19 pandemic-in terms of transferrable technical and nontechnical skills and wellbeing. DESIGN: This was a survey study consisting of a 23-point questionnaire. SETTING: The study involved surgical trainees that had been redeployed to the (ICU) across all hospitals in London during the COVID-19 pandemic. PARTICIPANTS: The survey was sent to 90 surgical trainees who were between postgraduate years 2 to 4. Trainees in specialty training programs (>5 years after graduation) were not included. Thirty-two trainees responded to the questionnaire and were included in the study results. RESULTS: All respondents spent between 4 and 8 weeks working in ICU. Prior to redeployment, 78% of participants had previous experience of ICU or an affiliated specialty, and >90% had attended at least 1 educational course with relevance to ICU. There were statistically significant increases in confidence performing central venous cannulation and peripheral arterial catheterisation (p < 0.05). With regards to clinical skills, respondents reported feeling more confident managing ventilated patients, patients on noninvasive ventilation, dialysis, and circulatory failure patients after working in ICU. Respondents (97%) felt that the experience would be beneficial to their future careers but 53% felt the redeployment had a negative impact on their mental health. CONCLUSIONS: Redeployment of surgical trainees to ICU led to increased confidence in a number of technical and nontechnical skills. However, proactive interventions are needed for training surgeons with regard to their psychological wellbeing in these extraordinary circumstances and to improve workforce planning for future pandemics.
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COVID-19 , Pandemias , Cuidados Críticos , Humanos , Londres , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
Lower gastrointestinal bleeding (LGIB) is a serious and potentially life-threatening condition warranting hospital admission. The most frequent causes include diverticular disease, colitis, hemorrhoids, neoplasm, inflammatory bowel disease, and varices. Varices usually occur secondary to liver cirrhosis and are frequently located in the gastroesophageal region. Those occurring elsewhere are known as ectopic varices. The diagnosis and management of ectopic varices is challenging, and guidelines are not currently available. We report the case of recurrent large-volume hematochezia secondary to a cecal varix in a 60-year-old female with alcoholic liver cirrhosis. Initial investigation with CT angiography and endoscopy failed to identify the source of bleeding. A second CT angiogram identified a large varix in the cecum, and the patient was successfully managed with radiological embolization and transjugular intra-hepatic porto-systemic shunt (TIPSS).