Biologically effective dose (BED) value lower than 120 Gy improve outcomes in lung SBRT.

BACKGROUND: Lung SBRT has a well-defined role in the treatment of patients with early stage non-small cell lung cancer who are not surgical candidates or refuse surgery. Biologically effective dose (BED) of greater than or equal to 100 Gy has been recommended. However, optimal fractionation remains unclear. Our objective was analyze patients treated with lung SBRT in our institution and evaluate outcomes according prescribed dose. PATIENTS AND METHODS: One hundred nine patients with early non-small cell lung cancer and treated with lung SBRT were retrospectively analyzed. Differences between dose received, local control, and survival were evaluated. For comparison of BEDs, the prescribed dose for SBRT was stratified according to two groups: high (BED > 120 Gy) and low (BED < 120 Gy). RESULTS: A relationship between mortality and total dose (54.7 Gy ± 4.8) was observed. Significantly worse survival was observed for patients with higher total doses (p < 0.003). It was found that patients receiving BED > 120 had increased mortality compared to patients receiving BED < 120 (p = 0.021). It was observed mean dose/fraction 12.6 Gy/f was a protective factor and decreased the probability of death. CONCLUSION: Our data suggest that mean total dose lower 54 and a calculated BED < 120 Gy is the optimal. Further prospective data are needed to confirm these results and determine the optimal dose fractionation scheme as a function of tumor size and location of volume.

Lung and diaphragm ultrasound as predictors of success in weaning from mechanical ventilation.

BACKGROUND: Lung and diaphragm ultrasound methods have recently been introduced to predict the outcome of weaning from mechanical ventilation (MV). The aim of this study is to assess the reliability and accuracy of these techniques for predicting successful weaning in critically ill adults. METHODS: We conducted two studies: a cross-sectional interobserver agreement study between two sonographers and a prospective cohort study to assess the accuracy of lung and diaphragm ultrasound for predicting weaning and extubation outcome. For the interobserver agreement study, we included 50 general critical care patients who were consecutively admitted to the ICU. For the predictive accuracy study, we included consecutively 69 patients on MV who were ready for weaning. We assessed interobserver agreement of ultrasound measurements, using the weighted kappa coefficient for LUSm score (modified lung ultrasound score) and the intraclass correlation coefficient (ICC) and Bland-Altman method for TI (diaphragm thickening index). We assessed the predictive value of LUSm and TI in weaning outcome by plotting the corresponding ROC curves. RESULTS: We found adequate interobserver agreement for both LUSm (weighted kappa 0.95) and TI (ICC 0.78, difference according to Bland-Altman analysis ± 12.5%). LUSm showed good-moderate discriminative power for successful weaning and extubation (area under the ROC curve (AUC) for successful weaning 0.80, and sensitivity and specificity at optimal cut-off point 0.76 and 0.73, respectively; AUC for successful extubation 0.78, and optimal sensitivity and specificity 0.76 and 0.47, respectively. TI was more sensitive but less specific for predicting successful weaning (AUC 0.71, optimal sensitivity and specificity 0.93 and 0.48) and successful extubation (AUC 0.76, optimal sensitivity and specificity 0.93 and 0.58). The area under the ROC curve for predicting weaning success was 0.83 for both ultrasound measurements together. CONCLUSIONS: Interobserver agreement was excellent for LUSm and moderate-good for TI. A low TI value or high LUSm value indicates high risk of weaning failure.

Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide.

OBJECTIVES: To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. MATERIAL AND METHODS: Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O2-) and H2O2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time. Hif-1α, SOD1, SOD2 and NQO1 were determined by immunolabeling. Catalase activity was measured by classic enzymatic assay. Glutathione levels and total antioxidant capacity were quantified using commercial kits. RESULTS: CoQ did not affect oxygen consumption but reduced the level of O2- and H2O2 while shifted to a pro-oxidant cell status mainly due to a decrease in catalase activity and SOD2 level. Hif-1α was dampened, echoed by a decrease lactate and several key metabolites involved in glutathione synthesis. CoQ-treated cells were twofold more sensitive than control to radiation-induced DNA damage and apoptosis in short and long-term clonogenic assays, potentiating TMZ-induced cytotoxicity, without affecting non-transformed astrocytes. CONCLUSIONS: CoQ acts as sensitizer for cytotoxic therapies, disarming GBM cells, but not normal astrocytes, against further pro-oxidant injuries, being potentially useful in clinical practice for this fatal pathology.

Diaphragm and Lung Ultrasound to Predict Weaning Outcome: Systematic Review and Meta-Analysis.

BACKGROUND: Deciding the optimal timing for extubation in patients who are mechanically ventilated can be challenging, and traditional weaning predictor tools are not very accurate. The aim of this systematic review and meta-analysis was to assess the accuracy of lung and diaphragm ultrasound for predicting weaning outcomes in critically ill adults. METHODS: MEDLINE, the Cochrane Library, Web of Science, Scopus, LILACS, Teseo, Tesis Doctorales en Red, and OpenGrey were searched, and the bibliographies of relevant studies were reviewed. Two researchers independently selected studies that met the inclusion criteria and assessed study quality in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The summary receiver-operating characteristic curve and pooled diagnostic OR (DOR) were estimated by using a bivariate random effects analysis. Sources of heterogeneity were explored by using predefined subgroup analyses and bivariate meta-regression. RESULTS: Nineteen studies involving 1,071 people were included in the study. For diaphragm thickening fraction, the area under the summary receiver-operating characteristic curve was 0.87, and DOR was 21 (95% CI, 11-40). Regarding diaphragmatic excursion, pooled sensitivity was 75% (95% CI, 65-85); pooled specificity, 75% (95% CI, 60-85); and DOR, 10 (95% CI, 4-24). For lung ultrasound, the area under the summary receiver-operating characteristic curve was 0.77, and DOR was 38 (95% CI, 7-198). Based on bivariate meta-regression analysis, a significantly higher specificity for diaphragm thickening fraction and higher sensitivity for diaphragmatic excursion was detected in studies with applicability concerns. CONCLUSIONS: Lung and diaphragm ultrasound can help predict weaning outcome, but its accuracy may vary depending on the patient subpopulation.

Accuracy of Lung Ultrasonography in the Diagnosis of Pneumonia in Adults: Systematic Review and Meta-Analysis.

BACKGROUND: Some studies suggest that lung ultrasonography could be useful for diagnosing pneumonia; moreover, it has a more favorable safety profile and lower cost than chest radiography and CT. The aim of this study was to assess the accuracy of bedside lung ultrasonography for diagnosing pneumonia in adults through a systematic review and meta-analysis. METHODS: We searched MEDLINE, Scopus, The Cochrane Library, Web of Science, DARE, HTA Database, Google Scholar, LILACS, ClinicalTrials.gov, TESEO, and OpenGrey. In addition, we reviewed the bibliographies of relevant studies. Two researchers independently selected studies that met the inclusion criteria. Quality of the studies was assessed in accordance with the Quality Assessment of Diagnostic Accuracy Studies tool. The summary receiver operating characteristic (SROC) curve and a pooled estimation of the diagnostic odds ratio (DOR) was estimated using a bivariate random-effects analysis. The sources of heterogeneity were explored using predefined subgroup analyses and bivariate meta-regression. RESULTS: Sixteen studies (2,359 participants) were included. There was significant heterogeneity of both sensitivity and specificity according to the Q test, without clear evidence of threshold effect. The area under the SROC curve was 0.93, with a DOR at the optimal cutpoint of 50 (95% CI, 21-120). A tendency toward a higher area under the SROC curve in high-quality studies was detected; however, these differences were not significant after applying the bivariate meta-regression. CONCLUSIONS: Lung ultrasonography can help accurately diagnose pneumonia, and it may be promising as an adjuvant resource to traditional approaches.

Correction of systematic set-up error in breast and head and neck irradiation through a no-action level (NAL) protocol.

PURPOSE: To quantify systematic and random patient set-up errors in breast and head and neck conventional irradiation and to evaluate a no-action level (NAL) protocol for systematic set-up error off-line correction in head and neck cancer and breast cancer patients. MATERIAL AND METHODS: Verification electronic portal images of orthogonal set-up fields were obtained daily for the initial four consecutive fractions for 20 patients treated for breast cancer and for 20 head and neck cancer patients. The calculated systematic error was used to shift the isocentre accordingly on the fifth treatment day. From then until the end of the treatment course, pair orthogonal portal images of set-up fields were obtained weekly. To assess the impact of the protocol, pre- and post-correction systematic errors were compared and PTV margins were estimated before and after correction using published margin recipes. RESULTS: Population systematic set-up error decreased in the breast cancer patient group after the implementation of NAL protocol from 4.0 to 1.7 mm on the x-axis, from 4.7 to 2.1 mm on the y-axis and from 2.8 to 0.9 mm on the z axis. The percentage of patients with individual systematic set-up error reduction was 80%, 90% and 80% on the x-, y and z-axes respectively. Population systematic set-up error decreased also in the head and neck cancer patient group from 2.3 to 1.1 mm on the x-axis, from 1.6 to 1.4 mm on the y-axis and from 1.7 to 0.7 mm on the z-axis. The percentage of patients with individual systematic set-up error reduction was 70%, 65% and 85% on the x-, y- and z-axes respectively. Margin reduction achievable with NAL protocol implementation on the x-, y- and z-axes was 6.3, 7.2 and 4.8 mm for breast cancer patients and 3.3, 0.6 and 2.8 mm for head and neck cancer patients. CONCLUSION: NAL off-line protocol is useful for systematic set-up error correction and PTV margin reduction in conventional breast and head and neck irradiation.

Autoimmune thyroiditis presenting as palmoplantar keratoderma.

Palmoplantar keratoderma is a heterogeneous group of hereditary and acquired disorders characterized by abnormal thickening of palms and soles. Hypothyroidism is an unusual cause of palmoplantar keratoderma, rarely reported in the literature. We report a case of a 43-year-old woman presented with a 3-month history of a diffuse palmoplantar hyperkeratosis unresponsive to topical keratolytics and corticosteroids. Her past medical and family histories were unremarkable. She complained of recent asthenia, mood changes and constipation. Laboratory evaluation revealed an autoimmune thyroiditis with hypothyroidism. Other causes of acquired palmoplantar keratoderma were excluded. After hormonal replacement therapy institution, a gradual improvement of skin condition was observed. The diagnosis of underlying causes for acquired palmoplantar keratoderma can be a difficult task; however its recognition is essential for successful treatment results. Although a very rare association, hypothyroidism must be suspected in patients with acquired palmoplantar keratoderma, particularly when it occurs in association with systemic symptoms.