Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer.

BACKGROUND: Standard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC. METHODS: In this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival. RESULTS: After a median follow-up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab-combination group and in 68.2% of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs. 6.4%). CONCLUSIONS: In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435 .).

A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high-grade uterine sarcoma after stabilization or response to doxorubicin ± ifosfamide following surgery or in metastatic first line treatment (EORTC62113).

BACKGROUND: Uterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas. PRIMARY OBJECTIVE: To assess the efficacy of maintenance treatment with cabozantinib in patients with high-grade uterine sarcomas who achieved clinical benefit after standard chemotherapy. STUDY HYPOTHESIS: Maintenance treatment with cabozantinib after standard chemotherapy given as an adjuvant treatment after curative surgery, or in locally advanced or metastatic disease, increases progression-free survival compared with placebo TRIAL DESIGN: This is a randomized double blinded phase II trial. MAJOR INCLUSION/EXCLUSION CRITERIA: The study is enrolling adult patients with high-grade undifferentiated uterine sarcomas, high-grade endometrial stromal sarcomas, high-grade leiomyosarcoma, and high-grade adenosarcoma, FIGO (Federation International gynecologue Obstétricien) stage II/III to IV in stable disease or who achieved complete or partial response with doxorubicin ± ifosfamide, who are assigned 1:1 to 60 mg daily cabozantinib (experimental arm) or placebo (control arm), as maintenance therapy. Exclusion criteria include low-grade sarcoma. PRIMARY ENDPOINT: Progression-free survival at 4 months. SAMPLE SIZE: The study plans to enroll 90 patients to allow the randomization of 54 patients to detect an improvement in 4-month progression-free survival from 50% to 80% with 15% significance level and 85% power. Estimated dates for accrual completion: recruitment for the trial started in February 2015, and has currently enrolled 83 patients, of whom 35 patients have been randomized. The end of recruitment is anticipated for December 2020. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT01979393.

MicroRNA-profiling of miR-371~373- and miR-302/367-clusters in serum and cerebrospinal fluid identify patients with intracranial germ cell tumors.

PURPOSE: Intracranial germ cell tumors (iGCT) comprise germinoma and non-germinoma. Their diagnosis predominantly relies on biopsy as only one-fifth of patients present with elevated biomarkers (AFP/ß-HCG) in serum or cerebrospinal fluid (CSF). MicroRNAs (miR/miRNA) have emerged as non-invasive biomarkers in extracranial GCT and may potentially facilitate non-invasive diagnosis in iGCT. METHODS: We analyzed eight miRNAs in serum and CSF from the miR-371~373- and miR-302/367-clusters and four miRNAs differentially expressed in iGCT tissue (miR-142-5p/miR-146a-5p/miR-335-5p/miR-654-3p) from eight iGCT patients (age 10-33 years) and 12 control subjects by pre-amplified RT-qPCR. MiR-30b-5p (serum) and miR-204-5p (CSF) acted as reference genes. ΔCt-values were expressed as [Formula: see text] after standardization against controls. RESULTS: Between iGCT and control patients' serum ΔCt-values of miR-371a-3p (p = 0.0159), miR-372-3p (p= 0.0095, miR-367 (p = 0.0190), miR-302a (p = 0.0381) and miR-302d-3p (p = 0.0159) differed significantly. Discriminatory pattern in CSF was similar to serum as miR-371a (p = 0.0286), miR-372-3p (p = 0.0028), miR-367-3p (p = 0.0167) and miR-302d-3p (p = 0.0061) distinguished between patients and controls. Abundant [Formula: see text] levels of each of these miRNAs were found across all serum and CSF samples including biomarker-negative patients. CONCLUSION: With the largest data set so far, we underline the suitability of miR-371a, miR-372, miR-367 and miR-302d in serum and CSF for diagnosis of iGCT, particularly in biomarker-negative germinoma. Diagnosis of iGCT by miRNA analysis is a feasible and valid approach, particularly as serum can be readily obtained by a less invasive procedure. MiRNA analysis may discriminate iGCT from other tumors with similar radiological findings and may allow to monitor response to therapy as well as early relapse during follow-up.

Diagnostics of autoimmune bullous diseases in German dermatology departments.

BACKGROUND: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments. METHODS: A standardized questionnaire evaluated the available diagnostic methods i. e. direct immunofluorescence microscopy (IFM), indirect IFM, commercial ELISA systems, and non-commercial serological tests as well as the number of samples per year in all 34 university and 39 non-university dermatology departments. RESULTS: The overall return rate was 89 %, 100 % and 79 % for the university and non-university departments, respectively. Direct IFM was the most frequently used method and was applied in 98 % of the responding departments. In 74 % of the responding departments, indirect IFM was used mainly on monkey esophagus and human salt-split skin. Commercial ELISA systems were employed in 58 % of the clinics; all of them used anti-desmoglein ELISA, while anti-BP180 and anti-BP230 ELISA were established in 49 % and 48 % of departments, respectively. Non-commercial analytic methods were only performed in 22 % of the departments. CONCLUSIONS: The high return rate of this survey allows a relatively precise description of the current diagnostic methods used in German dermatology departments. Standard diagnostic tests are available nationwide and in bullous pemphigoid and pemphigus, the antigen-specific detection of autoantibodies is routinely performed in half of the departments. Rare disorders may be diagnosed by cooperation with some specialized centers.

Hypofractionated preoperative radiotherapy for high risk soft tissue sarcomas in a geriatric patient population.

BACKGROUND: Standard therapy for localised, resectable high risk soft tissue sarcomas consists of wide excision and radiotherapy over several weeks. This treatment schedule is hardly feasible in geriatric and frail patients. In order not to withhold radiotherapy from these patients, hypofractionated radiotherapy with 25 Gy in 5 fractions was evaluated in a geriatric patient population. PATIENTS AND METHODS: A retrospective analysis was performed of 18 geriatric patients with resectable high risk soft tissue sarcomas of extremities and thoracic wall. Wound healing and short term oncologic outcome were analysed. In addition, dose constraints for radiotherapy of the extremities were transferred from normofractionated to hypofractionated radiotherapy regimens. RESULTS: Feasibility was good with 17/18 patients completing treatment as planned. Wound healing complication rate was in the range of published data. Two patients developed local and distant recurrence, two patients isolated distant recurrences. No isolated local recurrences were observed. Keeping the constraints was possible in all cases without compromising the coverage of the target volume. CONCLUSIONS: Hypofractionated radiotherapy and surgery was well tolerated even in this specific patient population. With feasibility concerning early wound healing problems and adapted constraints, which allow for the treatment of most resectable extremity tumours, the concept warrants further evaluation in patients unfit for standard radiotherapy.

Morgellons in dermatology.

Delusional parasitosis (DP) is the most frequent delusional disorder in dermatology. In DP there is a fixed belief of a usually skin-related invasion or infestation by a number of alleged infectious species (usually parasites and bacteria), whose identity has varied over the decades. Since 2002 worldwide an increasing number of patients have complained of unverifiable fibers and filaments in or on the skin, associated with numerous nonspecific complaints (arthralgias, altered cognitive function and extreme fatigue). This entity has been named "Morgellons disease" by the patients themselves, although medical evidence for its existence is lacking. As an example, we discuss a 55-year-old woman who complained of Morgellons disease and was treated as if she had DP. Currently the delusional assumption of infestation with Morgellons should be considered as a new type of DP with some kind of inanimate material. We therefore recommend in case of DP including Morgellons the use of the broader term "delusional infestation".

MR Thermometry Data Correlate with Pathological Response for Soft Tissue Sarcoma of the Lower Extremity in a Single Center Analysis of Prospectively Registered Patients.

Background: There is a strong biologic rationale for using locoregional hyperthermia in soft tissue sarcoma and a randomized trial reported significant improvements with hyperthermia. The aim of this study was to describe the opportunities of magnetic resonance (MR)-based thermometry in a cohort of soft tissue sarcoma patients undergoing combined radiotherapy and locoregional hyperthermia. Patients and Methods: For eleven evaluable patients, tumor volume (VTu) and a separate volume for temperature analysis with reliable temperature distribution (Vtherm) were contoured for every hyperthermia treatment (103 therapies). Temperature data were recorded for all tumors and were correlated with clinical features and pathologic response data. Results: Of 48 patients with high-risk soft tissue sarcomas treated with radio(chemo)therapy and locoregional hyperthermia, MR thermometry was possible in 11 (23%) patients. For all patients, the temperature superseded by 90% of VTu (T90(VTu)) and T90 (Vtherm) were in the range of 37-43 °C and 40-45 °C, respectively. Larger tumors tended to reach higher temperatures. For tumors showing a pathologic response in the resection specimen after preoperative treatment, temperature (T90 (Vtherm)) was significantly higher than in tumors without pathologic response. Conclusion: Lower extremity sarcomas undergoing preoperative treatment with locoregional hyperthermia are especially suitable for MR thermometry. MR thermometry is a promising non-invasive way for temperature measurement during locoregional hyperthermia, showing a positive dose-response relationship.

Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up.

Importance: Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients with operable gastrointestinal stromal tumor (GIST), but its influence on overall survival (OS) has remained uncertain. Objective: To evaluate the effect of adjuvant imatinib on OS of patients who have a high estimated risk for GIST recurrence after macroscopically complete surgery. Design, Setting, and Participants: In this open-label, randomized (1:1), multicenter phase 3 clinical trial conducted in Finland, Germany, Norway, and Sweden, 400 patients who had undergone macroscopically complete surgery for GIST with a high estimated risk for recurrence according to the modified National Institutes of Health Consensus Criteria were enrolled between February 2004 and September 2008. Data for this follow-up analysis were analyzed from September to November, 2019. Interventions: Imatinib 400 mg/d administered orally for either 12 months or 36 months after surgery. Main Outcomes And Measures: The primary end point was RFS; the secondary objectives included OS and treatment safety. Results: The intention-to-treat cohort consisted of 397 patients (12-month group, 199; 36-month group, 198; 201 men and 196 women; median [IQR] age, 62 (51-69) years and 60 (51-67) years, during a median follow-up time of 119 months after the date of randomization, 194 RFS events and 96 OS events were recorded in the intention-to-treat population. Five-year and 10-year RFS was 71.4% and 52.5%, respectively, in the 36-month group and 53.0% and 41.8% in the 12-month group (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87; P = .003). In the 36-month group, 5-year OS and 10-year OS rates were 92.0% and 79.0%, respectively, and in the 12-month group 85.5% and 65.3% (HR, 0.55; 95% CI, 0.37-0.83; P = .004). The results were similar in the efficacy population, from which 15 patients who did not have GIST in central pathology review and 24 patients who had intra-abdominal metastases removed at surgery were excluded (36-month group, 10-year OS 81.6%; 12-month group, 66.8%; HR, 0.50; 95% CI, 0.32-0.80; P = .003). No new safety signals were detected. Conclusions and Relevance: Three years of adjuvant imatinib is superior in efficacy compared with 1 year of imatinib. Approximately 50% of deaths may be avoided during the first 10 years of follow-up after surgery with longer adjuvant imatinib treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT00116935.

A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407.

INTRODUCTION: In the randomized KEYNOTE-407 study (ClinicalTrials.gov, NCT02775435), pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC. We report updated efficacy outcomes from the protocol-specified final analysis and, for the first time, progression on next line of treatment. METHODS: Eligible patients were randomized to chemotherapy plus either pembrolizumab (n = 278) or placebo (n = 281). After positive results from the second interim analysis, patients still receiving placebo could cross over to pembrolizumab monotherapy at the time of confirmed progressive disease. The primary end points were OS and PFS. PFS-2 (time from randomization to progression on next-line treatment/death, whichever occurred first) was an exploratory end point. RESULTS: After median (range) follow-up of 14.3 (0.1-31.3) months, pembrolizumab plus chemotherapy continued to exhibit a clinically meaningful improvement over placebo plus chemotherapy in OS (median, 17.1 mo [95% confidence interval (CI): 14.4‒19.9] versus 11.6 mo [95% CI: 10.1‒13.7]; hazard ratio [HR], 0.71 [95% CI: 0.58‒0.88]) and PFS (median, 8.0 mo [95% CI: 6.3‒8.4] versus 5.1 mo [95% CI: 4.3‒6.0]; HR, 0.57 [95% CI: 0.47‒0.69]). PFS-2 was longer for patients randomized to first-line pembrolizumab plus chemotherapy (HR, 0.59 [95% CI: 0.49‒0.72]). Grade 3 to 5 adverse events occurred in 74.1% and 69.6% of patients receiving pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively. CONCLUSIONS: Pembrolizumab plus chemotherapy continued to exhibit substantially improved OS and PFS in patients with metastatic squamous NSCLC. The PFS-2 outcomes support pembrolizumab plus chemotherapy as a standard first-line treatment in patients with metastatic squamous NSCLC.

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer.

PURPOSE: In the phase 3 KEYNOTE-407 study, the addition of pembrolizumab to carboplatin-paclitaxel/nab-paclitaxel significantly improved overall survival, progression-free survival, and objective response rate in patients with previously untreated metastatic squamous non-small-cell lung cancer (NSCLC), with little impact on severe toxicity. We present patient-reported outcomes (PROs) from KEYNOTE-407. METHODS: Patients were randomly assigned to receive 4 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus carboplatin plus paclitaxel or nab-paclitaxel, followed by pembrolizumab or placebo for an additional 31 cycles. Health-related quality of life (HRQoL) was evaluated using the European Organisation for Research and Treatment of Cancer Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Lung Cancer Module 13 (QLQ-LC13). Key PRO endpoints were change from baseline to weeks 9 and 18 (during and after platinum therapy) in the QLQ-C30 global health status/quality of life (GHS/QoL) score and time to deterioration in the composite endpoint of cough, chest pain, or dyspnea from the QLQ-C30 and QLQ-LC13. Two-sided, nominal P values are provided. RESULTS: A total of 554 and 553 patients completed ≥ 1 QLQ-C30 or ≥ 1 QLQ-LC13 assessment, respectively. GHS/QoL score improved for the pembrolizumab-combination group (least squares [LS] mean [95% CI] change from baseline: week 9, 1.8 [-0.9 to 4.4]; week 18, 4.3 [1.7 to 6.9]) and deteriorated in the placebo-combination group (week 9, -1.8 [-4.4 to 0.7]; week 18, -0.57 [-3.3 to 2.2]). Between-group differences were improved for the pembrolizumab-combination group (difference in LS mean scores: week 9, 3.6 [95% CI, 0.3 to 6.9], nominal P = .0337; week 18, 4.9 [1.4 to 8.3], nominal P = .0060). Median time to deterioration in cough, chest pain, or dyspnea was not reached in either group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06]; nominal P = .125). CONCLUSION: Addition of pembrolizumab to chemotherapy maintained or improved HRQoL measurements relative to baseline and improved HRQoL versus chemotherapy alone at weeks 9 and 18. These results support use of pembrolizumab plus chemotherapy as first-line therapy for metastatic squamous NSCLC.

[Lifestyle drugs in medicine]. / Lifestyle-Medikamente in der Medizin.

Lifestyle drugs have become an important new group of medications, which are taken by healthy people to increase the individual well-being and quality of life. Nootropics, psychopharmaceuticals, hormones and "ecodrugs" are today the main groups. The wish for eternal youth, beauty and potency is central, and lifestyle medications are also requested to influence cosmetic findings, which are usually simply a result of the natural aging process. Lifestyle drugs seem to be harmless, but the physician must pay attention to possible abuse, side effects, risks and complications. Additionally, however, lifestyle drugs are also frequently used by patients suffering from emotional disorders such as somatoform disorders. Medicalization of physiological life is then expected to solve psychosocial problems, but without success. The use of lifestyle medications in somatoform disorders is contraindicated and psychotherapy or psychopharmacological treatment come first. With this overview article, we would like to make an update of new lifestyle drugs.

Simultaneous dual-band ultra-high resolution optical coherence tomography.

Ultra-high resolution optical coherence tomography (OCT) imaging is demonstrated simultaneously at 840 nm and 1230 nm central wavelength using an off-the-shelf turn-key supercontinuum light source. Spectral filtering of the light source emission results in a double peak spectrum with average powers exceeding 100 mW and bandwidths exceeding 200 nm for each wavelength band. A free-space OCT setup optimized to support both wavelengths in parallel is introduced. OCT imaging of biological tissue ex vivo and in vivo is demonstrated with axial resolutions measured to be < 2 mum and < 4 mum at 840 nm and 1230 nm, respectively. This measuring scheme is used to extract spectroscopic features with outstanding spatial resolution enabling enhanced image contrast.

Psychosomatic disturbances and cosmetic surgery.

Medical activity in recent years has experienced a marked expansion of possibilities for aesthetic surgery, usually requested by patients. Especially in dermatology, an increasing demand for and use of doctor/medical services by healthy individuals has resulted in a drastic change to cosmetic dermatology. The request for cosmetic surgery is emotionally or psychosocially motivated. Patients with psychological disturbances sometimes push aside possible risks and complications or deny side effects and interactions of the procedures. Subjective impairments of appearance, feelings of inferiority and social pho-bias may be in the background of somatizing disorders. These emotional disorders, such as body dysmorphic disorder, personality disorder or polysurgical addiction, often remain undiscovered but should be excluded in any patient receiving cosmetic procedures.

Short-term inspiratory muscle training potentiates the benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program.

OBJECTIVE: To investigate the efficiency of short-term inspiratory muscle training program associated with combined aerobic and resistance exercise on respiratory muscle strength, functional capacity and quality of life in patients who underwent coronary artery bypass and are in the phase II cardiac rehabilitation program. METHODS: A prospective, quasi-experimental study with 24 patients who underwent coronary artery bypass and were randomly assigned to two groups in the Phase II cardiac rehabilitation program: inspiratory muscle training program associated with combined training (aerobic and resistance) group (GCR + IMT, n=12) and combined training with respiratory exercises group (GCR, n=12), over a period of 12 weeks, with two sessions per week. Before and after intervention, the following measurements were obtained: maximal inspiratory and expiratory pressures (PImax and PEmax), peak oxygen consumption (peak VO2) and quality of life scores. Data were compared between pre- and post-intervention at baseline and the variation between the pre- and post-phase II cardiac rehabilitation program using the Student's t-test, except the categorical variables, which were compared using the Chi-square test. Values of P<0.05 were considered statistically significant. RESULTS: Compared to GCR, the GCR + IMT group showed larger increments in PImax (P<0.001), PEmax (P<0.001), peak VO2 (P<0.001) and quality of life scores (P<0.001). CONCLUSION: The present study demonstrated that the addition of inspiratory muscle training, even when applied for a short period, may potentiate the effects of combined aerobic and resistance training, becoming a simple and inexpensive strategy for patients who underwent coronary artery bypass and are in phase II cardiac rehabilitation.

Short-term inspiratory muscle training potentiates the benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program / Treinamento muscular inspiratório de curto prazo potencializa os benefícios do treinamento aeróbico e resistido em pacientes após CRM na fase II de programa de reabilitação cardíaca

AbstractObjective:To investigate the efficiency of short-term inspiratory muscle training program associated with combined aerobic and resistance exercise on respiratory muscle strength, functional capacity and quality of life in patients who underwent coronary artery bypass and are in the phase II cardiac rehabilitation program.Methods:A prospective, quasi-experimental study with 24 patients who underwent coronary artery bypass and were randomly assigned to two groups in the Phase II cardiac rehabilitation program: inspiratory muscle training program associated with combined training (aerobic and resistance) group (GCR + IMT, n=12) and combined training with respiratory exercises group (GCR, n=12), over a period of 12 weeks, with two sessions per week. Before and after intervention, the following measurements were obtained: maximal inspiratory and expiratory pressures (PImax and PEmax), peak oxygen consumption (peak VO2) and quality of life scores. Data were compared between pre- and post-intervention at baseline and the variation between the pre- and post-phase II cardiac rehabilitation program using the Student's t-test, except the categorical variables, which were compared using the Chi-square test. Values of P<0.05 were considered statistically significant.Results:Compared to GCR, the GCR + IMT group showed larger increments in PImax (P<0.001), PEmax (P<0.001), peak VO2 (P<0.001) and quality of life scores (P<0.001).Conclusion:The present study demonstrated that the addition of inspiratory muscle training, even when applied for a short period, may potentiate the effects of combined aerobic and resistance training, becoming a simple and inexpensive strategy for patients who underwent coronary artery bypass and are in phase II cardiac rehabilitation.

ResumoObjetivo:Avaliar os efeitos de um programa de treinamento muscular inspiratório em curto prazo associado ao exercício aeróbio e resistido na força muscular respiratória, capacidade funcional e qualidade de vida de pacientes submetidos à cirurgia de revascularização do miocárdio, na Fase II da Reabilitação Cardíaca.Métodos:Trata-se de um estudo quase-experimental, prospectivo, com amostra de 24 pacientes submetidos à cirurgia de revascularização do miocárdio alocados aleatoriamente para Fase II da Reabilitação Cardíaca em dois grupos: grupo de treinamento muscular inspiratório associado ao treinamento combinado (aeróbio e resistido) (GRC + TMI, n=12) e grupo treinamento combinado e exercícios respiratórios (GRC, n=12) durante um período de 12 semanas, com 2 sessões semanais. Antes e após a intervenção, as seguintes mensurações foram obtidas: pressão inspiratória e expiratória máxima (PImáx e PEmáx), consumo de oxigênio de pico (VO2pico) e escore de qualidade de vida. Os dados foram comparados entre o momento pré e pós-intervenção na linha de base e a variação entre o pré e pós-programa de reabilitação cardíaca com uso do teste t de Student, exceto as variáveis categóricas, que foram comparadas pelo teste de qui-quadrado. Foi considerado um P<0,05.Resultados:Comparado ao GRC, o GRC + TMI apresentou maior incremento tanto na PImáx (P<0,001) quanto na PEmáx (P<0,001), no VO2pico (P<0,001) e na qualidade de vida (P<0,001).Conclusão:Demonstrou-se que a adição do programa de treinamento muscular inspiratório, mesmo quando aplicada por um curto período, pode complementar os efeitos do exercício aeróbio combinado ao resistido, tornando-se uma estratégia benéfica para pacientes submetidos à cirurgia de revascularização do miocárdio na Fase II da reabilitação cardíaca.

Visualization of the basement membrane zone of the bladder by optical coherence tomography: feasibility of noninvasive evaluation of tumor invasion.

OBJECTIVES: Imaging techniques with high resolution are evolving rapidly for medical applications and may substitute invasive diagnostic techniques. The use of ultrahigh resolution optical coherence tomography (UHR-OCT) to image healthy and morphologically altered bladder tissue with virtual histology is evaluated ex vivo to define parameters necessary for future, diagnostically relevant in vivo systems. Here, special focus is on the visualization of the basement membrane zone. METHODS: Optical coherence tomography examinations were performed by using a modified commercial OCT system comprising a Ti:sapphire femtosecond laser to support an enhanced resolution of 3 microm axial x 10 microm lateral. Tomograms of 142 fresh human bladder tissue samples from cystectomies, radical prostatectomies, and transurethral tumor resections were recorded and referenced to histologic sections using standard hematoxylin and eosin staining. RESULTS: OCT of normal bladder mucosa allows for a clear differentiation of urothelium and lamina propria. The basement membrane zone is identified as a narrow, low-scattering band between these layers. This allows for reliable exclusion of invasion. Healthy urothelial tissue, carcinoma in situ, and transitional cell carcinoma can be differentiated using this imaging technique. Sensitivity of UHR-OCT for malignant bladder tissue could be determined to be 83.8%, and specificity to be 78.1%. CONCLUSIONS: UHR-OCT is considered promising in the attempt to strive for fluorescence cystoscopy-guided virtual histology as a means of supporting therapeutic decisions for bladder neoplasia.

Expression of prothrombin, thrombin and its receptors in human scars.

The coagulation system is thought to play a pivotal role during the initial phase of wound healing, but mechanisms and cells involved are only partly understood. We have therefore examined human scars for the expression of thrombin, its precursor prothrombin and the thrombin receptors, thrombomodulin (TM) and protease-activated receptor-1 (PAR-1), compared with normal skin. Biopsies of scars were obtained from primary excision sites of melanoma patients (n = 20) and were compared with normal skin distant from the scar (n = 10), using immunohistochemistry. In addition, polymerase chain reaction analyses were performed on scar versus normal tissue and on cultured keratinocytes, fibroblasts and endothelial cells before and after stimulation with selected cytokines known to be active in wound healing. Normal epidermis was stained for prothrombin, thrombin, TM and PAR-1, and dermal tissue was stained only for TM and PAR-1. In scar tissue, thrombin and TM were upregulated in the epidermis and all four molecules in the dermis, independent of the age of the scars. In tissue extracts, mRNA expression of PAR-1 and prothrombin expression were, however, unchanged and TM even slightly decreased in scars, compared with normal skin. On analysis of cultured cells, keratinocytes expressed mRNA for PAR-1, TM and prothrombin, endothelial cells for PAR-1 and TM, and fibroblasts for PAR-1. An upregulation of PAR-1 mRNA was induced in fibroblasts on exposure to tumor necrosis factor-alpha (TNF-alpha), while it remained unchanged in endothelial cells in response to TNF-alpha. A downregulation of TM was induced in endothelial cells on exposure to TNF-alpha. These findings, showing a marked modulation of thrombin, PAR-1 and TM even in older human scar tissue, suggest that the coagulation system is not only involved during clotting, but also during the inflammatory and tissue remodelling phases of wound healing.

[Squamous cell carcinoma in lupus vulgaris]. / Carcinoma in lupo.

Lupus vulgaris and carcinoma in lupo have become rare events that take place in the developed countries only under special circumstances. A 53-year-old woman developed such a carcinoma. She suffered from alcoholism, a well known risk factor for tuberculosis. The diagnosis of lupus vulgaris was confirmed by biopsy when an erythematous lesion on her arm that had been present for 25 years enlarged and subsequently ulcerated. Chemotherapy was discontinued because of lack of compliance and the ulcer grew markedly over the following 16 months. Therefore the entire lesion was excised. Histology showed a squamous cell carcinoma within the ulcer. Neither further systemic manifestations of tuberculosis nor metastases of the carcinoma were found. Under continuous combined antituberculous therapy, the patient remained free of symptoms. This case underlines the problems associated with a disease that has been nearly forgotten in the western countries. It also shows that alcoholism is a risk factor for tuberculosis, along with debilitating diseases such as lymphoma and AIDS as well as immunosuppressive therapy.

Novel spot-like pigmentary pattern detected by high-resolution epiluminescence microscopy.

BACKGROUND: Epiluminescence light microscopy (ELM) can be improved with enhanced optical resolution. OBJECTIVE: High-resolution ELM was performed by placing a standard light microscope on the skin surface for visualization of further details. METHODS: 25 melanocytic nevi and 14 melanomas with a globular pattern were investigated and examined histologically. RESULTS: A new spotty substructure was detected, namely individual pigmented spots of 5-10 micro m in diameter located within peripheral brown globules. Clinicopathologic correlation showed these spots to correspond with individual pigmented melanocytes (IPMs) within nests of melanocytes. IPMs were seen in 9/25 melanocytic nevi and in none of 14 melanomas. CONCLUSION: Their origin may be a physiologic, UV-dependent pigment induction suggesting that they may represent a benign ELM pattern.

Detection of a novel pigment network feature in reticulated black solar lentigo by high-resolution epiluminescence microscopy.

Epiluminescence light microscopy (ELM) of pigmented skin lesions has led to a catalog of pigment network (PN) features. The objective of this study was to determine whether high-resolution ELM detects additional pigment structures not seen with conventional ELM. Epiluminescence light microscopy was performed by placing the lens of a standard light microscope directly on the skin surface, with resulting enhanced optical resolution compared with ELM systems currently in general use. Eight reticulated black solar lentigines were studied. All lesions were viewed and analyzed using dermatoscopic criteria for the PN. In addition, they were all photographed, excised, and examined histologically. Two subtypes of black solar lentigines could be distinguished using generally accepted dermatoscopic criteria for the PN. Furthermore, a new pigment structure was detected, namely, pigment spots of equal color, shape, and size, which were regularly superimposed on and juxtaposed to the PN. Clinicopathologic correlation showed these spots to represent individual hyperpigmented corneocytes. Because such cells result from physiologic excessive pigment translocation via the epidermal melanocytic unit, we called them pigmented corneocytes. Pigmented corneocytes were seen in seven of eight black solar lentigines. The ELM technique presented here allows for more detailed analysis and classification of the PN components. Pigmented corneocytes are proposed as an additional dermatoscopic criterion.