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Ossicular destruction is a common phenomenon in chronic otitis media due to an imbalance between osteoblasts and osteoclasts. Computed tomography helps us in the assessment of ossicular status, extent of pneumatization, and early identification of complications. This study aims to check the diagnostic accuracy of computed tomography temporal bone for the detection of ossicular erosion in comparison with the surgical findings taken as a gold standard. The use of this investigation as an adjunct can prove to be helpful in planning mastoid exploration as well as a primary reconstruction surgery especially in mucosal and early squamosal diseases. It's a cross-sectional validation study done on 50 patients with chronic otitis media (both mucosal and squamous type) from July 2022 to November 2023. Patients underwent CT scanning of temporal bone and ossicular status was reported by the radiologist. Later on, mastoid surgery was carried out and per operative findings were documented. 2 × 2 tables were formed and diagnostic accuracy of CT temporal bone was checked in terms of sensitivity, specificity, negative predictive value, and positive predictive value. The results revealed that CT temporal bone has a high diagnostic accuracy with a sensitivity of 92.5% and specificity of 100% for malleus (p value < 0.001). For incus and stapes, sensitivity came out to be 93.5% and 76% respectively and specificity values were 94.7% and 100% (p value < 0.001 for all) giving a verdict that the pre-operative use of this radiological investigation should be encouraged by otologists.
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Introduction: Cerebrospinal Fluid (CSF) rhinorrhea results from breakdown in the integrity of structures separating the subarachnoid space and nasal cavity, namely subarachnoid space and dura mater, the bony skull base and periostea alongside the upper aerodigestive tract mucosa. Endoscopic repair is considered the treatment of choice for CSF rhinorrhea. Our aim of study was to analyze the etiopathogenesis and outcomes of treatment. Material and Methods: A retrospective study review of patients treated with endoscopic repair of CSF rhinorrhea at tertiary care hospital in ENT Department Benazir Bhutto hospital Rawalpindi from august 2013 to September 2017 identified 25 patients. Majority of them were male. The defects were closed in three layers using fat, fascia lata and nasal mucosa along with fibrin sealant in majority of patients. Pre operatively subarachnoid drain was placed in all patients. Patients were followed up to 3 months. Results: Forty-four patients underwent endoscopic repair of CSF rhinorrhea. The age group ranged from 16 to 55 years. Of the total of 44 patients 26 (59%) were males and 18(41%) females. The mean age of the patients in our study was 32.8 ± 9.7. Post trauma CSF leak was seen up to 52.3% of the patients. The most common site of leakage was identified Cribriform plate area. Our success rate of endoscopic repair was 88.6%. The most commonly observed complication was meningitis that was observed in 2 (4.5%) of the patients that too were managed conservatively. Conclusion: Accurate localization of site of leakage appears to be essential for successful endoscopic repair of CSF rhinorrhea. In our study cribriform plate area was commonly observed area of CSF leak. In our study, the success rate was 88.6% and low complication rate 4.5%.
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OBJECTIVES: To compare functional outcomes and complication rates of anterolateral advancement pharyngoplasty (ALA) versus barbed reposition pharyngoplasty (BRP) in the treatment of obstructive sleep apnea patients with palatal and lateral pharyngeal wall collapse. STUDY DESIGN: Prospective study. SETTING: University hospitals. SUBJECTS AND METHODS: Forty-six patients were included in this study. Patients were divided into two groups randomly, group 1 (23 cases) underwent anterolateral advancement pharyngoplasty and group 2 (23 cases) underwent barbed relocation pharyngoplasty. According to the following criteria: both sex, age between 18 and 65 years, body mass index ≤ 32 kg/m2, Friedman stage II or III, type I Fujita, nocturnal polysomnography study diagnostic for OSA, retropalatal and lateral pharyngeal wall collapse, diagnosis with flexible nasoendoscopy during a Muller's maneuver based on a 5-point scale and drug-induced sleep endoscopy. Patients who suffered from retroglossal airway collapse were rolled out. RESULTS: Apnea-hypopnea index decreased from 27.50 ± 11.56 to 11.22 ± 7.63 (P ≤ .001) in group 1 and from 33.18 ± 10.94 to 12.38 ± 6.77 (P ≤ .001) in group 2. Retropalatal posterior airway space increased from 9.84 ± 1.29 mm to 21.48 ± 2.8 mm (P ≤ .001) in group 1 and increased from 10.26 ± 1.2 mm to 22.86 ± 2.62 mm (P ≤ .001) in group 2. Retropalatal space volume increased from 1.9 ± 0.68 cm3 to 2.75 ± 0.7 cm3 (P ≤ .001) in group 1 and increased from 1.96 ± 0.88 cm3 to 2.82 ± 0.83 cm3 (P ≤ .001) in group 2. Surgical success was 86.95% in group 1 compared to 82.6% in group 2. CONCLUSIONS: Both techniques appear to be effective with a high surgical success rate in the treatment of OSA patients with retropalatal and lateral pharyngeal wall collapse.
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Faringe , Apneia Obstrutiva do Sono , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Palato , Faringe/cirurgia , Estudos Prospectivos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/etiologia , Resultado do Tratamento , Masculino , FemininoRESUMO
An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd immunity. Although this strategy has proved successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies1. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to respond rapidly to respiratory virus infections2-6. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to the extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8+ T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8+ T cells requires the antiviral cytokine interferon-γ (IFNγ) and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8+ T cells in the respiratory tract can have important roles in protecting the host against viral disease and limiting viral spread throughout the population.
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Linfócitos T CD8-Positivos , Memória Imunológica , Células T de Memória , Infecções por Paramyxoviridae , Sistema Respiratório , Animais , Camundongos , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Imunidade Coletiva/imunologia , Memória Imunológica/imunologia , Interferon gama/imunologia , Células T de Memória/imunologia , Paramyxoviridae/imunologia , Paramyxoviridae/fisiologia , Infecções por Paramyxoviridae/imunologia , Infecções por Paramyxoviridae/prevenção & controle , Infecções por Paramyxoviridae/transmissão , Infecções por Paramyxoviridae/virologia , Sistema Respiratório/citologia , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , Transcrição Gênica , HumanosRESUMO
Introduction: The journal club is widely used in most postgraduate programs of medical institutes; however, the use of journal clubs in undergraduate medical programs is nearly absent or very rare. Aim: The aim of this work is to document the insertion of the journal club as a method for learning in the undergraduate starting with the endocrinology/endocrine surgery module to be fully implemented in all modules of the MBBS of FMBU. In addition, the study aimed to outline the steps of designing a journal club by following specific procedures and Identification of students' and faculty satisfaction through 5-years implementation of the journal club. Material and Methods: A total of 453 students representing the five consecutive batches of medical students from 2019 to 2023 who studied the endocrinology/endocrine surgery module were entered into the study. Following guidelines for implementation of the journal clubs that were adopted by the quality and accreditation committee, the faculty select the types of papers from the articles chosen by students. The papers discussed were case reports, original research, and review articles. The students were asked to formulate critical appraisal topics, PICO, for each paper. A 20-question test was applied to all participants. The students' attendance, scores, and students/faculty satisfaction were estimated. Results: A total of 50 papers were discussed in the 5-year journal club 15 case reports (30%), 26 original research (52%), and 9 review articles (18%). The student's attendance ranged from 72.53±3.74 to 98.07±3.15. The students and faculty's satisfaction were 3.52 and 3.82 respectively. The mean Students' score in A 20-question test in a 5-year journal club was 76.93 ± 9.78 and the lowest score was in the 2nd batch (online batch). Conclusion: The insertion of a well-structured journal club in the undergraduate medical program is necessary to improve the knowledge including knowledge among students. In addition, journal clubs inspire students to be lifelong learners.
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PURPOSE: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS: A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort (P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers (P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower (P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase (P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION: A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.
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COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Vacinas contra COVID-19 , Formação de Anticorpos , SARS-CoV-2 , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , COVID-19/prevenção & controle , Anticorpos Antivirais , Imunização , Vacinação , Anticorpos Neutralizantes , RNA Mensageiro , Vacinas de mRNARESUMO
PURPOSE: Patients with non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) are at higher risk of severe SARS-CoV-2 infection. We investigated vaccine-induced antibody responses in patients with NHL/CLL against the original SARS-CoV-2 strain and variants of concern including B.1.167.2 (Delta) and B.1.1.529 (Omicron). MATERIALS AND METHODS: Blood from 121 patients with NHL/CLL receiving two doses of vaccine were collected longitudinally. Antibody binding against the full-length spike protein, the receptor-binding, and N-terminal domains of the original strain and of variants was measured using a multiplex assay. Live-virus neutralization against Delta, Omicron, and the early WA1/2020 strains was measured using a focus reduction neutralization test. B cells were measured by flow cytometry. Correlation between vaccine response and clinical factors was determined. RESULTS: Mean anti-SARS-CoV-2 spike immunoglobulin G-binding titers were 85-fold lower in patients with NHL/CLL compared with healthy controls, with seroconversion occurring in only 67% of patients. Neutralization titers were also lower and correlated with binding titers (P < .0001). Treatment with anti-CD20-directed therapies within 1 year resulted in 136-fold lower binding titers. Peripheral blood B-cell count also correlated with vaccine response. At 3 months from last anti-CD20-directed therapy, B-cell count ≥ 4.31/µL blood around the time of vaccination predicted response (OR 7.46, P = .04). Antibody responses also correlated with age. Importantly, neutralization titers against Delta and Omicron were reduced six- and 42-fold, respectively, with 67% of patients seropositive for WA1/2020 exhibiting seronegativity for Omicron. CONCLUSION: Antibody binding and live-virus neutralization against SARS-CoV-2 and its variants of concern including Delta and Omicron were substantially lower in patients with NHL/CLL compared with healthy vaccinees. Anti-CD20-directed therapy < 1 year before vaccination and number of circulating B cells strongly predict vaccine response.
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COVID-19 , Leucemia Linfocítica Crônica de Células B , Linfoma não Hodgkin , Vacinas , COVID-19/prevenção & controle , Humanos , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma não Hodgkin/terapia , SARS-CoV-2 , Vacinas Sintéticas , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Vacinas de mRNARESUMO
Humoral immunity is a major component of the adaptive immune response against viruses and other pathogens with pathogen-specific antibody acting as the first line of defense against infection. Virus-specific antibody levels are maintained by continual secretion of antibody by plasma cells residing in the bone marrow. This raises the important question of how the virus-specific plasma cell population is stably maintained and whether memory B cells are required to replenish plasma cells, balancing their loss arising from their intrinsic death rate. In this study, we examined the longevity of virus-specific antibody responses in the serum of mice following acute viral infection with three different viruses: lymphocytic choriomeningitis virus (LCMV), influenza virus, and vesicular stomatitis virus (VSV). To investigate the contribution of memory B cells to the maintenance of virus-specific antibody levels, we employed human CD20 transgenic mice, which allow for the efficient depletion of B cells with rituximab, a human CD20-specific monoclonal antibody. Mice that had resolved an acute infection with LCMV, influenza virus, or VSV were treated with rituximab starting at 2 months after infection, and the treatment was continued for up to a year postinfection. This treatment regimen with rituximab resulted in efficient depletion of B cells (>95%), with virus-specific memory B cells being undetectable. There was an early transient drop in the antibody levels after rituximab treatment followed by a plateauing of the curve with virus-specific antibody levels remaining relatively stable (half-life of 372 days) for up to a year after infection in the absence of memory B cells. The number of virus-specific plasma cells in the bone marrow were consistent with the changes seen in serum antibody levels. Overall, our data show that virus-specific plasma cells in the bone marrow are intrinsically long-lived and can maintain serum antibody titers for extended periods of time without requiring significant replenishment from memory B cells. These results provide insight into plasma cell longevity and have implications for B cell depletion regimens in cancer and autoimmune patients in the context of vaccination in general and especially for COVID-19 vaccines. IMPORTANCE Following vaccination or primary virus infection, virus-specific antibodies provide the first line of defense against reinfection. Plasma cells residing in the bone marrow constitutively secrete antibodies, are long-lived, and can thus maintain serum antibody levels over extended periods of time in the absence of antigen. Our data, in the murine model system, show that virus-specific plasma cells are intrinsically long-lived but that some reseeding by memory B cells might occur. Our findings demonstrate that, due to the longevity of plasma cells, virus-specific antibody levels remain relatively stable in the absence of memory B cells and have implications for vaccination.
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Anticorpos Antivirais , Coriomeningite Linfocítica , Células B de Memória , Rituximab , Animais , Anticorpos Antivirais/sangue , Humanos , Imunidade Humoral , Memória Imunológica , Coriomeningite Linfocítica/imunologia , Células B de Memória/citologia , Camundongos , Camundongos Transgênicos , Infecções por Orthomyxoviridae/imunologia , Plasmócitos/citologia , Infecções por Rhabdoviridae/imunologia , Rituximab/farmacologiaRESUMO
Background: Dry eye is described as a multifactorial disorder of the tear film that occurs due to excessive tear evaporation or tears insufficiency, and so leads to ocular discomfort sensation and ocular tissue damage with time. Objective: To assess the incidence of dry eye disease after uncomplicated phacoemulsification surgery in patients with no pre-existed dry eye. Patients and Methods: This hospital-based cross-sectional study was conducted to assess the incidence of dry eye at 100 eyes of 100 patients who underwent uncomplicated phacoemulsification surgery, with age more than 45 years old. It is measured by dry eye tests Schirmer 1 and tear break up time. Results: This study showed that 22% of the patients who underwent uncomplicated phacoemulsification surgery suffered from dry eye with significant results at 1st week post-operative that improved over time. Conclusion: There was a statistically significant drop in the results of the Schirmer test 1 and TBUT post phacoemulsification surgery, but with no clinical significance as they still at the normal range. The tear film assessment results at the 1st week post-operative were out of the normal range with TBUT and were borderline with ST1 in 22% of the patients. These results improved over time to return to the normal values within 12 weeks postoperatively.
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PURPOSE: We investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants. METHODS: 82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated. RESULTS: Binding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=<0.0001). More importantly, NSCLC patients had reduced live-virus neutralizing activity compared to the healthy vaccinees (P=<0.0001). Spike and RBD-specific binding IgG titers peaked after a week following the second vaccine dose and declined after six months (P=<0.001). While patients >70 years had lower IgG titers (P=<0.01), patients receiving either PD-1 monotherapy, chemotherapy or a combination of both did not have a significant impact on the antibody response. Binding antibody titers to the Delta and Beta variants were lower compared to the WT strain (P=<0.0001). Importantly, we observed significantly lower FRNT50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=<0.0001) in NSCLC patients. CONCLUSIONS: Binding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.
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OBJECTIVES: Polycythaemia vera (PV) is a condition that may potentially put patients undergoing cardiac surgery at an increased risk of bleeding and thrombosis; however, there is currently a paucity of literature regarding the management of these patients. We aim to examine the literature in this systematic review to indicate the interventions that may be considered to minimise complications. METHODS: We conducted a literature search using keywords and MeSH terms to identify articles discussing PV and cardiac surgery. The studies were identified and qualitatively analysed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. RESULTS: In total, 10 case reports representing 11 patients were identified for this systematic review and were included in qualitative analysis. 63.6% of patients had preoperative intermittent phlebotomy, and the majority of patients received postoperative therapy that involved one antiplatelet agent and one anticoagulant. Generous perioperative fluid management, phlebotomy, preservation of core body temperature, early extubation, monitoring of myocardial ischaemia, infarction and vascular events, intense chest physiotherapy and patient mobilisation are important to consider to reduce the risk of complications arising from surgery. CONCLUSION: These considerations should be systematically discussed in a multidisciplinary team, where the acute surgical need can be balanced appropriately against the risk of haemorrhage and thrombosis.
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Policitemia Vera , Trombose , Anticoagulantes/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Humanos , Inibidores da Agregação Plaquetária , Policitemia Vera/induzido quimicamente , Policitemia Vera/complicações , Policitemia Vera/terapia , Trombose/etiologiaRESUMO
Abdominal pain is a common presentation to the emergency department (ED) and the differential diagnoses is broad. Intussusception is more common in children, with only 5% of cases reported in adults. 80%-90% of adult intussusception is due to a well-defined lesion resulting in a lead point, whereas in children, most cases are idiopathic. The most common site of involvement in adults is the small bowel. Treatment in adults is generally operative management whereas in children, a more conservative approach is taken with non-operative reduction. We present a case of a 54-year-old woman who presented to our ED with severe abdominal pain and vomiting. CT of the abdomen revealed a jejunojejunal intussusception. The patient had an urgent laparoscopy and small bowel resection of the intussusception segment was performed. Histopathological examination of the resected specimen found no pathologic lead point and, therefore, the intussusception was determined to be idiopathic.
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Intussuscepção , Laparoscopia , Dor Abdominal/etiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Intestino Delgado , Intussuscepção/diagnóstico por imagem , Intussuscepção/etiologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Re-exploration of bleeding after cardiac surgery is associated with significant morbidity and mortality. Perioperative blood loss and rate of re-exploration are variable among centers and surgeons. OBJECTIVE: To present our experience of low rate of re-exploration based on adopting checklist for hemostasis and algorithm for management. METHODS: Retrospective analysis of medical records was conducted for 565 adult patients who underwent surgical treatment of congenital and acquired heart disease and were complicated by postoperative bleeding from Feb 2006 to May 2019. Demographics of patients, operative characteristics, perioperative risk factors, blood loss, requirements of blood transfusion, morbidity and mortality were recorded. Logistic regression was used to identify predictors of re-exploration and determinants of adverse outcome. RESULTS: Thirteen patients (1.14%) were reexplored for bleeding. An identifiable source of bleeding was found in 11 (84.6%) patients. Risk factors for re-exploration were high body mass index, high Euro SCORE, operative priority (urgent/emergent), elevated serum creatinine and low platelets count. Re-exploration was significantly associated with increased requirements of blood transfusion, adverse effects on cardiorespiratory state (low ejection fraction, increased s. lactate, and prolonged period of mechanical ventilation), longer intensive care unit stay, hospital stay, increased incidence of SWI, and higher mortality (15.4% versus 2.53% for non-reexplored patients). We managed 285 patients with severe or massive bleeding conservatively by hemostatic agents according to our protocol with no added risk of morbidity or mortality. CONCLUSION: Low rate of re-exploration for bleeding can be achieved by strict preoperative preparation, intraoperative checklist for hemostasis implemented by senior surgeons and adopting an algorithm for management.
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Algoritmos , Procedimentos Cirúrgicos Cardíacos , Lista de Checagem , Hemostasia Cirúrgica/normas , Assistência Perioperatória/normas , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Hemostasia Cirúrgica/métodos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Reoperação , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: St. Thomas (ST) and Del Nido (DN) cardioplegic solutions are widely used for myocardial protection during cardiac surgery. In 2016, our university hospital shifted from modified St. Thomas to Del Nido solution for both adult and pediatric cardiac surgery. This retrospective study was conducted to compare ST and DN solutions regarding surgical workflow and clinical outcome in pediatric and adult patients undergoing cardiac surgery. METHODS: We reviewed 220 patients who underwent cardiac surgery requiring cardioplegic arrest. Patients were categorized in 2 groups: ST (n = 110) and DN (n = 110). Each group included 60 pediatric and 50 adult patients. Demographic, intraoperative, and postoperative variables were collected. RESULTS: In pediatric patients, no significant difference was found between the 2 groups regarding clamping time, bypass time, need for defibrillation, inotropic score, postoperative ejection fraction (EF), period of mechanical ventilation, intensive care unit stay, or postoperative arrhythmias. One patient in the ST group required mechanical support by extracorporeal membrane oxygenation. We had 5 cases of pediatric mortality (3 in DN and 2 in ST, P = .64). In adult patients, significantly fewer patients in the DN group needed defibrillation than in the ST group. No significant difference was found regarding clamping time, inotropic score, or intraaortic balloon pump use. Mortality in adult patients was 6 cases (4 in ST group and 2 in DN group). CONCLUSION: DN cardioplegia solution is as safe as ST solution in pediatric and adult cardiac surgery. It has comparable results of myocardial protection and clinical outcome, with superiority regarding uninterrupted surgery and lower rate of defibrillation.
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Procedimentos Cirúrgicos Cardíacos/métodos , Eletrólitos/farmacologia , Parada Cardíaca Induzida/métodos , Lidocaína/farmacologia , Sulfato de Magnésio/farmacologia , Manitol/farmacologia , Cloreto de Potássio/farmacologia , Bicarbonato de Sódio/farmacologia , Soluções/farmacologia , Adolescente , Adulto , Bicarbonatos/farmacologia , Cloreto de Cálcio/farmacologia , Soluções Cardioplégicas/farmacologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Magnésio/farmacologia , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Cloreto de Sódio/farmacologia , Adulto JovemRESUMO
A major question in immunology is what role antigen load plays in determining the size of the CD8 immune response. Is the amount of antigen important during recruitment, proliferation, and/or memory formation? Animal studies have shown that antigen is only strictly required early during activation of T cells, but the importance of antigen at later timepoints is unclear. Using data from 24 volunteers infected with the yellow fever vaccine virus (YFV), we analyzed the dependence of T cell proliferation upon viral load. We found that volunteers with high viral load initially have greater T cell responses, but by 28 days post-vaccination those with lower viral load are able to 'catch-up.' Using differential equation modeling we show that this pattern is consistent with viral load only affecting recruitment (i.e., programmed proliferation) as opposed to affecting recruitment and proliferation (i.e., antigen-dependent proliferation). A quantitative understanding of the dependence of T cell dynamics on antigen load will be of use to modelers studying not only vaccination, but also cancer immunology and autoimmune disorders.
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Linfócitos T CD8-Positivos/imunologia , Modelos Imunológicos , Febre Amarela/imunologia , Animais , Antígenos Virais , Linfócitos T CD8-Positivos/patologia , Proliferação de Células , Humanos , Memória Imunológica , Modelos Lineares , Ativação Linfocitária , Conceitos Matemáticos , Fatores de Tempo , Vacinação , Carga Viral/imunologia , Febre Amarela/prevenção & controle , Febre Amarela/virologia , Vacina contra Febre Amarela/imunologia , Vírus da Febre Amarela/imunologiaRESUMO
Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.
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Vacinas contra a AIDS/uso terapêutico , Antígenos CD4/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , HIV-1/genética , Vacinas contra a AIDS/imunologia , Adolescente , Adulto , Sítios de Ligação , Feminino , HIV-1/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune responses with these features are induced by prime-boost strategies, using heterologous vectors, heterologous inserts, or a combination of both. METHODS: A total of 180 participants were randomly assigned to receive combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen. RESULTS: T-cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means, 1.0; 95% confidence interval [CI], .6-1.6; P = .91), but heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means, 2.7; 95% CI, 1.2-5.7; P = .01). Participants in the heterologous versus homologous insert groups had T-cell responses that targeted epitopes with greater evolutionary conservation (mean entropy [±SD], 0.32 ± 0.1 bits; P = .003), and epitopes recognized by responders provided higher coverage (49%; P = .035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (P = .02, .044, and .045, respectively). CONCLUSIONS: These data demonstrate that vaccination with heterologous insert prime boosting increased T-cell responses to shared epitopes, while heterologous vector prime boosting increased the number of T-cell epitopes recognized. CLINICAL TRIALS REGISTRATION: NCT01095224.
Assuntos
Vacinas contra a AIDS/imunologia , HIV-1/imunologia , Linfócitos T/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Vacinas contra a AIDS/administração & dosagem , Adenoviridae/genética , Adolescente , Adulto , Método Duplo-Cego , Portadores de Fármacos , Epitopos de Linfócito T/imunologia , Feminino , Vetores Genéticos , Antígenos HIV/genética , Antígenos HIV/imunologia , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Adulto Jovem , Produtos do Gene env do Vírus da Imunodeficiência Humana/genéticaRESUMO
OBJECTIVE: To determine sleep deprivation and its consequences on doctors in tertiary care hospitals. METHODS: The cross-sectional study was conducted from February to May 2012 and comprised house officers and postgraduate trainees at 4 public and 1 private tertiary care hospitals in Karachi. The subjects were posted in wards, out-patient departments and emergencies. A proforma was designed with questions about duration of duty hours, sleep deprivation and its effects on quality of performance, and presence of anxiety, depression, medical errors, frequent cold and infections, accidents, weight changes, and insomnia. Duration of 1 hour was given to fill the proforma. SPSS 20 was used for data analysis. RESULT: The study comprised 364 subjects: 187 (51.37%) house officers and 177 (48.62%) postgraduate trainees. There were 274 (75.27%) females and 90 (24.72%) males. Of those who admitted to being sleep deprived (287; 78.84%), also complained of generalised weakness and poor performance (n = 115; 40%), anxiety (n = 110; 38%), frequent cold and infections (n = 107; 37%), personality changes (n = 93; 32%), depression (n = 86; 30%), risk of accidents (n = 68; 23.7%), medical errors (n = 58; 20%) and insomnia (n = 52; 18%). CONCLUSION: Having to spend 80-90 hours per week in hospitals causes sleep deprivation and negative work performance among doctors. Also, there is anxiety, depression and risk of accidents in their personal lives.
Assuntos
Educação de Pós-Graduação em Medicina , Internato e Residência , Privação do Sono/complicações , Privação do Sono/psicologia , Ansiedade/etiologia , Resfriado Comum/etiologia , Depressão/etiologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Erros Médicos , Paquistão , Distúrbios do Início e da Manutenção do Sono/etiologia , Inquéritos e Questionários , Análise e Desempenho de Tarefas , Tolerância ao Trabalho Programado/fisiologia , Tolerância ao Trabalho Programado/psicologiaRESUMO
Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different vaccine candidates can be compared in early phases of evaluation.