Prognosis of polymerase epsilon (POLE) mutation in high-grade endometrioid endometrial cancer: Systematic review and meta-analysis.

BACKGROUND: POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior. OBJECTIVES: To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models. RESULTS: This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I2 = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I2 = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I2 = 68%, 18 studies). CONCLUSION: POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.

Correlation between chest computed tomography findings and pulmonary function test results in the post-recovery phase of COVID-19.

OBJECTIVE: The radiological and functional lung sequelae in COVID-19 survivors remain unclear. We compared the chest computed tomography findings of COVID-19 patients with normal and abnormal pulmonary function test results in the post-recovery phase. METHODS: The data of consecutive patients who underwent pulmonary function tests and chest computed tomography within 14 days after recovery from COVID-19 at two medical centers between May and October 2020 were collected retrospectively. Two thoracic radiologists who were blinded to the clinical information and pulmonary function test results classified the patients according to the computed tomography features, evidence of fibrotic-like changes, and semi-quantitative quantification of the extent of pulmonary abnormalities. The clinical characteristics and computed tomography findings of patients with normal pulmonary function test results were compared with those of patients with abnormal results. RESULTS: A total of 101 COVID-19 survivors, comprising 48 ambulatory and 53 hospitalized patients, were included at a median of 95 days from initial symptom onset. Computed tomography revealed fibrotic-like changes in 10.9% of patients. A reduction in the diffusion capacity of carbon monoxide was the most common lung function abnormality (19.8%). Abnormal diffusion capacity of carbon monoxide was associated with the presence and extension of lung opacities on chest computed tomography scans and fibrotic pulmonary abnormalities. The sensitivity, specificity, and accuracy of reduced diffusion capacity of carbon monoxide for detecting fibrotic-like pulmonary changes on chest computed tomography scans were 72.7%, 87.8%, and 86.1%, respectively. CONCLUSION: Our study suggests that the presence of an abnormal diffusion capacity of carbon monoxide in the post-recovery phase of COVID-19 is associated with a greater risk of long-term parenchymal lung disease, as evidenced by the presence of fibrotic-like changes on chest computed tomography scans, such as traction bronchiectasis and architectural distortion.

Correlation between chest computed tomography findings and pulmonary function test results in the post-recovery phase of COVID-19

ABSTRACT Objective The radiological and functional lung sequelae in COVID-19 survivors remain unclear. We compared the chest computed tomography findings of COVID-19 patients with normal and abnormal pulmonary function test results in the post-recovery phase. Methods The data of consecutive patients who underwent pulmonary function tests and chest computed tomography within 14 days after recovery from COVID-19 at two medical centers between May and October 2020 were collected retrospectively. Two thoracic radiologists who were blinded to the clinical information and pulmonary function test results classified the patients according to the computed tomography features, evidence of fibrotic-like changes, and semi-quantitative quantification of the extent of pulmonary abnormalities. The clinical characteristics and computed tomography findings of patients with normal pulmonary function test results were compared with those of patients with abnormal results. Results A total of 101 COVID-19 survivors, comprising 48 ambulatory and 53 hospitalized patients, were included at a median of 95 days from initial symptom onset. Computed tomography revealed fibrotic-like changes in 10.9% of patients. A reduction in the diffusion capacity of carbon monoxide was the most common lung function abnormality (19.8%). Abnormal diffusion capacity of carbon monoxide was associated with the presence and extension of lung opacities on chest computed tomography scans and fibrotic pulmonary abnormalities. The sensitivity, specificity, and accuracy of reduced diffusion capacity of carbon monoxide for detecting fibrotic-like pulmonary changes on chest computed tomography scans were 72.7%, 87.8%, and 86.1%, respectively. Conclusion Our study suggests that the presence of an abnormal diffusion capacity of carbon monoxide in the post-recovery phase of COVID-19 is associated with a greater risk of long-term parenchymal lung disease, as evidenced by the presence of fibrotic-like changes on chest computed tomography scans, such as traction bronchiectasis and architectural distortion.

A risk score for predicting death in COVID-19 in-hospital infection: A Brazilian single-center study.

BACKGROUND: There is a paucity of information about Brazilian COVID-19 in-hospital mortality probability of death combining risk factors. OBJECTIVE: We aimed to correlate COVID-19 Brazilian in-hospital patients' mortality to demographic aspects, biomarkers, tomographic, echocardiographic findings, and clinical events. METHODS: A prospective study, single tertiary center in Brazil, consecutive patients hospitalized with COVID-19. We analyzed the data from 111 patients from March to August 2020, performed a complete transthoracic echocardiogram, chest thoracic tomographic (CT) studies, collected biomarkers and correlated to in-hospital mortality. RESULTS: Mean age of the patients: 67 ± 17 years old, 65 (58.5%) men, 29 (26%) presented with systemic arterial hypertension, 18 (16%) with diabetes, 11 (9.9%) with chronic obstructive pulmonary disease. There was need for intubation and mechanical ventilation of 48 (43%) patients, death occurred in 21/111 (18.9%) patients. Multiple logistic regression models correlated variables with mortality: age (OR: 1.07; 95% CI 1.02-1.12; p: 0.012; age >74 YO AUC ROC curve: 0.725), intubation need (OR: 23.35; 95% CI 4.39-124.36; p < 0.001), D dimer (OR: 1.39; 95% CI 1.02-1.89; p: 0.036; value >1928.5 ug/L AUC ROC curve: 0.731), C-reactive protein (OR: 1.18; 95% CI 1.05-1.32; p < 0.005; value >29.35 mg/dl AUC ROC curve: 0.836). A risk score was created to predict intrahospital probability of death, by the equation: 3.6 (age >75 YO) + 66 (intubation need) + 28 (C-reactive protein >29) + 2.2 (D dimer >1900). CONCLUSIONS: A novel and original risk score were developed to predict the probability of death in Covid 19 in-hospital patients concerning combined risk factors.

Robot-assisted brachytherapy of the bladder with long distance support using video conferencing.

PURPOSE: The frontline treatment for localized muscle-invasive bladder carcinoma (MIBC) is radical cystectomy. However, a significant percentage of this population is elderly with either severe co-morbidities or suboptimal general health, increasing the per- and post-operative risk when undergoing a radical cystectomy. Conservative treatment options have been implemented such as robot-assisted laparoscopic brachytherapy (RALB), a minimally invasive therapeutic approach ensuring excellent results in terms of local control, survival, and low morbidity. The treatment was supported successfully long distance using videoconferencing by an expert group from the Netherlands. MATERIAL AND METHODS: An 81-year-old man was treated with RALB. The patient was submitted to external beam radiotherapy (EBRT) in a total dose of 40 Gy in 20 fractions. A partial cystectomy followed by implantation of three catheters along the scar and brachytherapy was completed. A total dose of 25 Gy in 10 fractions was administered with dose points calculated at 5 mm from the catheters. RESULTS: Dose planning was characterized by an homogeneity index of 62.3% and overdose index of 19.7%. Other conformity indexes were analyzed. Patient was discharged at the fourth day after the procedure. The clinical response after 6 months was documented. CONCLUSIONS: The previously reported good rates of tumor control and survival, and the excellent tolerance and low morbidity support RALB as a promising approach for selected groups of patients with localized MIBC. This case illustrates the ability to expand efficiently this technique, particularly among inexperienced medical teams.

Incidence of asthma symptoms and decreased pulmonary function in young amateur swimmers.

OBJECTIVE: To investigate the incidence of asthma symptoms in young amateur swimmers, and to describe the clinical treatment of the children with asthma in a private sports club in the city of São Paulo, Brazil. METHODS: The study included 171 amateur swimmers, ranging from 6 to14 years of age. All of the participants or their legal guardians were asked to complete the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and 119 were submitted to pulmonary function testing at rest. RESULTS: The overall incidence of asthma symptoms (ISAAC score > 6) among the swimmers was 16.8%. Of the 119 swimmers submitted to spirometry, 39 (32.7%) presented spirometric alterations (FEV1/FVC < 0.75). Among those with an ISAAC score > 6, there were 10 (31.2%) who stated that they were receiving no asthma treatment. Of those who reported receiving pharmacological treatment, 24% made use of bronchodilators but not of corticosteroids. CONCLUSIONS: The incidence of asthma symptoms and pulmonary function alterations among amateur swimmers within the 6-14 age bracket was high. In addition, a relevant proportion of these athletes were receiving no treatment.

Interaction between intra-abdominal pressure and positive-end expiratory pressure.

OBJECTIVE: The aim of this study was to quantify the interaction between increased intra-abdominal pressure and Positive-End Expiratory Pressure. METHODS: In 30 mechanically ventilated ICU patients with a fixed tidal volume, respiratory system plateau and abdominal pressure were measured at a Positive-End Expiratory Pressure level of zero and 10 cm H2O. The measurements were repeated after placing a 5 kg weight on the patients' belly. RESULTS: After the addition of 5 kg to the patients' belly at zero Positive-End Expiratory Pressure, both intra-abdominal pressure (p<0.001) and plateau pressures (p=0.005) increased significantly. Increasing the Positive-End Expiratory Pressure levels from zero to 10 cm H2O without weight on the belly did not result in any increase in intra-abdominal pressure (p=0.165). However, plateau pressures increased significantly (p< 0.001). Increasing Positive-End Expiratory Pressure from zero to 10 cm H2O and adding 5 kg to the belly increased intra-abdominal pressure from 8.7 to 16.8 (p<0.001) and plateau pressure from 18.26 to 27.2 (p<0.001). Maintaining Positive-End Expiratory Pressure at 10 cm H2O and placing 5 kg on the belly increased intra-abdominal pressure from 12.3 +/- 1.7 to 16.8 +/- 1.7 (p<0.001) but did not increase plateau pressure (26.6+/-1.2 to 27.2 +/-1.1 -p=0.83). CONCLUSIONS: The addition of a 5 kg weight onto the abdomen significantly increased both IAP and the airway plateau pressure, confirming that intra-abdominal hypertension elevates the plateau pressure. However, plateau pressure alone cannot be considered a good indicator for the detection of elevated intra-abdominal pressure in patients under mechanical ventilation using PEEP. In these patients, the intra-abdominal pressure must also be measured.

Interaction between intra-abdominal pressure and positive-end expiratory pressure

OBJECTIVE: The aim of this study was to quantify the interaction between increased intra-abdominal pressure and Positive-End Expiratory Pressure. METHODS: In 30 mechanically ventilated ICU patients with a fixed tidal volume, respiratory system plateau and abdominal pressure were measured at a Positive-End Expiratory Pressure level of zero and 10 cm H2O. The measurements were repeated after placing a 5 kg weight on the patients' belly. RESULTS: After the addition of 5 kg to the patients' belly at zero Positive-End Expiratory Pressure, both intra-abdominal pressure (p<0.001) and plateau pressures (p=0.005) increased significantly. Increasing the Positive-End Expiratory Pressure levels from zero to 10 cm H2O without weight on the belly did not result in any increase in intra-abdominal pressure (p=0.165). However, plateau pressures increased significantly (p< 0.001). Increasing Positive-End Expiratory Pressure from zero to 10 cm H2O and adding 5 kg to the belly increased intra-abdominal pressure from 8.7 to 16.8 (p<0.001) and plateau pressure from 18.26 to 27.2 (p<0.001). Maintaining Positive-End Expiratory Pressure at 10 cm H2O and placing 5 kg on the belly increased intra-abdominal pressure from 12.3 +/- 1.7 to 16.8 +/- 1.7 (p<0.001) but did not increase plateau pressure (26.6+/-1.2 to 27.2 +/-1.1 -p=0.83). CONCLUSIONS: The addition of a 5kg weight onto the abdomen significantly increased both IAP and the airway plateau pressure, confirming that intra-abdominal hypertension elevates the plateau pressure. However, plateau pressure alone cannot be considered a good indicator for the detection of elevated intra-abdominal pressure in patients under mechanical ventilation using PEEP. In these patients, the intra-abdominal pressure must also be measured.

[Pulmonary involvement in Behcet's disease: a positive single-center experience with the use of immunosuppressive therapy]. / Acometimento pulmonar na doença de Behçet: uma boa experiência com o uso de imunossupressores.

OBJECTIVE: Behcet's syndrome, or Behcet's disease (BD), is a multisystem pathology, and survival is related to pulmonary involvement. However, it appears that different treatments correlate with different prognoses. The aim of this study was to evaluate clinical and tomographic evolution, as well as the survival, of patients with BD-related pulmonary involvement. METHODS: A retrospective review of our experience with pulmonary manifestations in patients with BD treated at our institution between January 1, 1988 and April 30, 2006. The clinical, radiological, treatment and survival data were obtained from medical charts. RESULTS: We identified 9 patients with BD-related pulmonary involvement. The mean age was 34 +/- 11.5 years, and 7 of the patients were male. The radiological findings were as follows: pulmonary artery aneurysm (PAA) in 8 patients; pulmonary embolism in 3 (translating to an incidence of 5.11 cases/100 patient-years); alveolar hemorrhage in one; and pulmonary hypertension in one. The treatment consisted of immunosuppression with prednisone plus chlorambucil (or cyclophosphamide or mycophenolate mofetil) in all patients, with partial or complete resolution of the PAAs. One patient with a PAA and pulmonary hypertension also received sildenafil and warfarin, with good clinical and tomographic response (the first report in the English literature). In our sample, the mean duration of the follow-up period was 6.52 years. The three-year survival rate was 88.8%, as was the five-year survival rate. CONCLUSIONS: Patients with BD-related pulmonary involvement can present good survival with immunosuppressive therapy, and BD should be borne in mind as a possible cause of pulmonary hypertension and alveolar hemorrhage.

Acometimento pulmonar na doença de Behçet: uma boa experiência com o uso de imunossupressores / Pulmonary involvement in Behcet's disease: a positive single-center experience with the use of immunosuppressive therapy

OBJETIVO: A doença de Behçet (DB) representa uma patologia sistêmica, cuja sobrevida se relaciona com a presença de acometimento pulmonar. Entretanto, sugere-se que pacientes com diferentes tratamentos podem apresentar diferentes prognósticos. O objetivo deste estudo foi avaliar a evolução clínica e tomográfica, bem como a sobrevida deste pacientes com acometimento pulmonar relacionado à DB acompanhados em nosso serviço. MÉTODOS: Uma análise retrospectiva de nossa experiência com pacientes com acometimento pulmonar relaionado a DB acompanhados de 1 de Janeiro de 1988 a 30 de Abril de 2006. Os dados clínicos, radiológicos, terapêuticos e de sobrevida foram obtidos dos prontuários médicos. RESULTADOS: Foram identificados 9 pacientes, com idade média de 34 ± 11,5 anos, sendo 7 deles do sexo masculino. Os achados radiológicos foram aneurisma de artéria pulmonar (AAP) em 8 pacientes, embolia pulmonar em 3 (resultando em uma incidencia de 5,11 casos/100 paciente-anos), hemorragia alveolar em 1 e hipertensão pulmonar em 1 de 9 doentes. O tratamento consistiu-se de prednisona mais clorambucil (ou ciclofosfamida ou micofenolato de mofetil) em todos os 9 pacientes, com resolução total ou parcial dos AAP. O paciente com AAP e hipertensão pulmonar também recebeu sildenafil e warfarina, com boa resposta clínica e tomográfica. A sobrevida de nossos pacientes foi de 88,8 por cento em 3 e 5 anos, com acompanhamento médio de 6,52 anos. CONCLUSÕES: Pacientes com acometimento pulmonar relacionado à DB podem apresentar boa sobrevida com tratamento imunossupressor, e a DB deve ser lembrada como uma possível causa de hipertensão pulmonar e hemorragia alveolar.

OBJECTIVE: Behcet's syndrome, or Behcet's disease (BD), is a multisystem pathology, and survival is related to pulmonary involvement. However, it appears that different treatments correlate with different prognoses. The aim of this study was to evaluate clinical and tomographic evolution, as well as the survival, of patients with BD-related pulmonary involvement. METHODS: A retrospective review of our experience with pulmonary manifestations in patients with BD treated at our institution between January 1, 1988 and April 30, 2006. The clinical, radiological, treatment and survival data were obtained from medical charts. RESULTS: We identified 9 patients with BD-related pulmonary involvement. The mean age was 34 ± 11.5 years, and 7 of the patients were male. The radiological findings were as follows: pulmonary artery aneurysm (PAA) in 8 patients; pulmonary embolism in 3 (translating to an incidence of 5.11 cases/100 patient-years); alveolar hemorrhage in one; and pulmonary hypertension in one. The treatment consisted of immunosuppression with prednisone plus chlorambucil (or cyclophosphamide or mycophenolate mofetil) in all patients, with partial or complete resolution of the PAAs. One patient with a PAA and pulmonary hypertension also received sildenafil and warfarin, with good clinical and tomographic response (the first report in the English literature). In our sample, the mean duration of the follow-up period was 6.52 years. The three-year survival rate was 88.8 percent, as was the five-year survival rate. CONCLUSIONS: Patients with BD-related pulmonary involvement can present good survival with immunosuppressive therapy, and BD should be borne in mind as a possible cause of pulmonary hypertension and alveolar hemorrhage.

Vasculites pulmonares: quando suspeitar e como fazer o diagnóstico / Pulmonary vasculitis: when suspicion equal diagnosis

As vasculites pulmonares primárias são caracterizadas por processo inflamatório na parede dos vasos pulmonares que leva a isquemia e hemorragia pulmonar com as conseqüentes expressões clínicas e radiológicas. As vasculites pulmonares primárias são acompanhadas de expressão sistêmicas cutâneas, em nervos periféricos, rins, seios da face, olhos e ouvidos, além do trato gastrintestinal, e sistemas cardíaco e nervoso central. O diagnóstico é feito através da associação das informações clínicas, radiológicas e anatomopatológicas. O tratamento com corticosteróides e imunossupressores deve ser instituído precocemente e apresenta altas taxas de remissão.

Granulomatose de Wegener / Wegener's granulomatosis

A granulomatose de Wegener caracteriza-se por vasculite necrosante granulomatosa que acomete preferencialmente vias aéreas superiores, inferiores e rins. Seu diagnóstico é feito associando-se as manifestações clínicas, radiológicas (multiplos nódulos escavados) e os achados anatomopatológicos e o anticorpo anticitoplasma de neutrófilos positivo. O tratamento com corticosteróides e ciclofosfamida leva a 90 por cento de remissão da doença em 1 ano.

Síndrome de Churg-Strauss / Churg-Strauss syndrome

A síndrome de Churg-Strauss caracteriza-se por asma, eosinofilia e graus variados de vasculite sistêmica. As formas mais graves com acometimento cardíaco, gastrintestinal, sistema nervoso central e renal requerem ciclofosfamida para seu tratamento.

Mechanical ventilation in acute respiratory failure: recruitment and high positive end-expiratory pressure are necessary.

PURPOSE OF REVIEW: To review as best the critical care clinicians can recruit the acute respiratory distress syndrome (ARDS) lungs and keep the lungs opened, assuring homogeneous ventilation, and to present the experimental and clinical results of these mechanical ventilation strategies, along with possible improvements in patient outcome based on selected published medical literature from 1972 to 2004 (highlighting the period from June 2003 to June 2004 and recent results of the authors' group research). RECENT FINDINGS: In the experimental setting, repeated derecruitments accentuate lung injury during mechanical ventilation, whereas open lung concept strategies can attenuate lung injury. In the clinical setting, recruitment maneuvers improve short-term oxygenation in ARDS patients. A recent prospective clinical trial showed that low versus intermediate positive end-expiratory pressure (PEEP) levels (8 vs 13 cm H2O) associated with low tidal ventilation had the same effect on ARDS patient survival. Nevertheless, both conventional and electrical impedance thoracic tomography studies indicate that stepwise PEEP recruitment maneuvers increase lung volume and the recruitment percentage of lung tissue, and higher levels of PEEP (18-26 cm H2O) are necessary to keep the ARDS lungs opened and assure a more homogeneous low tidal ventilation. SUMMARY: Stepwise PEEP recruitment maneuvers can open collapsed ARDS lungs. Higher levels of PEEP are necessary to maintain the lungs open and assure homogenous ventilation in ARDS. In the near future, thoracic CT associated with high-performance monitoring of regional ventilation (electrical impedance tomography) may be used at the bedside to determine the optimal mechanical ventilation of ARDS patients.

Estudo da apoptose na granulomatose de Wegener / Study of apoptosis in Wegener’s granulomatosis

Foram analisados 50 pacientes com diagnóstico de granulomatose de Wegener (GW) atendidos no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, entre 1985 e 2000, de acordo com sexo e idade, sinais e sintomas. Destes 50 pacientes, 14 foram selecionados com material adequado para análise histológica, ensaio de TUNEL e imunohistoquímica para CD34. Como controles, biópsias de pacientes com vasculite leucocitoclástica e tuberculose. Apoptose foi positiva em 11 das 14 amostras dos pacientes com GW e ausente nos controles. As células foram confirmadas como endotélio pela imunohistoquímica para CD34. Apoptose pode ter um papel na patogênese da granulomatose de Wegener / We analyzed 50 patients with the diagnosis of Wegener’s granulomatosis (WG) from Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, from 1985 to 2000 regarding clinical presentation, sites of involvement and diagnostic procedures. Fourteen patients were selected with adequate tissue samples for histological analysis, TUNEL assay and CD34-immunohistochemistry. Biopsies from patients with leukocytoclastic vasculitis and tuberculosis were used as controls. Apoptosis was present in 11 of 14 patients with WG and in none of the controls, confirmed as endothelium by immunohistochemistry for CD34. Apoptosis may play a role in the pathogenesis of Wegener’s granulomatosis...