Search

Background: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation and infiltration of histiocytic cells., Methods: This review focused on the main aspects associated with LCH., Results: LCH can involve single or multiple organs and systems, with bone and skin being the most commonly affected sites. Regarding skeletal manifestations, the jawbones are involved in about 20%-30% of all cases. Such lesions may present as unilocular or multilocular images mainly affecting the posterior mandible. Oral soft tissue lesions may also occur, with the gingiva and hard palate being the most frequently affected sites., Conclusion: The diagnosis and management of LCH are challenging, requiring a multidisciplinary approach, with dentists playing a central role since oral manifestations can be the first sign of the condition., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The scant data about non-cystic fibrosis bronchiectasis, including tuberculosis sequelae and impairment of lung function, can bias the preoperative physiological assessment. Our goal was to evaluate the changes in lung function and exercise capacity following pulmonary resection in these patients; we also looked for outcome predictors., Methods: We performed a non-randomized prospective study evaluating lung function changes in patients with non-cystic fibrosis bronchiectasis treated with pulmonary resection. Patients performed lung function tests and cardiopulmonary exercise tests preoperatively and 3 and 9 months after the operation. Demographic data, comorbidities, surgical data and complications were collected., Results: Forty-four patients were evaluated for lung function. After resection, the patients had slightly lower values for spirometry: forced expiratory volume in 1 s preoperatively: 2.21 l ± 0.8; at 3 months: 1.9 l ± 0.8 and at 9 months: 2.0 l ± 0.8, but the relationship between the forced expiratory volume in 1 s and the forced vital capacity remained. The gas diffusion measured by diffusing capacity for carbon monoxide did not change: preoperative value: 23.2 ml/min/mmHg ± 7.4; at 3 months: 21.5 ml/min/mmHg ± 5.6; and at 9 months: 21.7 ml/min/mmHg ± 8.2. The performance of general exercise did not change; peak oxygen consumption preoperatively was 20.9 ml/kg/min ± 7.4; at 3 months: 19.3 ml/kg/min ± 6.4; and at 9 months: 20.2 ml/kg/min ± 8.0. Forty-six patients were included for analysis of complications. We had 13 complications with 2 deaths. To test the capacity of the predicted postoperative (PPO) values to forecast complications, we performed several multivariate and univariate analyses; none of them was a significant predictor of complications. When we analysed other variables, only bronchoalveolar lavage with positive culture was significant for postoperative complications (P = 0.0023). Patients who had a pneumonectomy had a longer stay in the intensive care unit (P = 0.0348)., Conclusions: The calculated PPO forced expiratory volume in 1 s had an excellent correlation with the measurements at 3 and 9 months; but the calculated PPO capacity for carbon monoxide and the PPO peak oxygen consumption slightly underestimated the 3- and 9-month values. However, none of them was a predictor for complications. Better tools to predict postoperative complications for patients with bronchiectasis who are candidates for lung resection are needed., Clinical Trial Registration Number: Clinicaltrials.gov: NCT01268475., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Lung cancer is a type of neoplasia with one of the highest incidences worldwide and is the largest cause of mortality due to cancer in the world today. It is classified according to its histological and biological characteristics, which will determine its treatment and prognosis. Non-small cell lung cancer accounts for 85% of the cases, and these are the cases that surgeons mostly deal with. Small cell lung cancer accounts for the remaining 15%. Surgery is the main method for treating early stage lung cancer, and lobectomy is the preferred procedure for treating primary lung cancer, while sublobar resection is an alternative for patients with poor reserve or with very small tumors. Surgeons need to be trained to use the resources and techniques available for lung resection, including less invasive approaches such as video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS), and need to be familiar with new oncological approaches, including curative, adjuvant or palliative treatments for patients with lung cancer.

Objective: in Latin America, especially Brazil, the use of a robotic platform for thoracic surgery is gradually increasing in recent years. However, despite tuberculosis and inflammatory pulmonary diseases are endemic in our country, there is a lack of studies describing the results of robotic surgical treatment of bronchiectasis. This study aims to evaluate the surgical outcomes of robotic surgery for inflammatory and infective diseases by determining the extent of resection, postoperative complications, operative time, and length of hospital stay., Methods: retrospective study from a database involving patients diagnosed with bronchiectasis and undergoing robotic thoracic surgery at three hospitals in Brazil between January of 2017 and January of 2020., Results: a total of 7 patients were included. The mean age was 47 + 18.3 years (range, 18-70 years). Most patients had non-cystic fibrosis bronchiectasis (n=5), followed by tuberculosis bronchiectasis (n=1) and lung abscess (n=1). The performed surgeries were lobectomy (n=3), anatomic segmentectomy (n=3), and bilobectomy (n=1). The median console time was 147 minutes (range 61-288 min.) and there was no need for conversion to open thoracotomy. There were no major complications. Postoperative complications occurred in one patient and it was a case of constipation with the need for an intestinal lavage. The median for chest tube time and hospital stay, in days, was 1 (range, 1-6 days) and 5 (range, 2-14 days) respectively., Conclusions: robotic thoracic surgery for inflammatory and infective diseases is a feasible and safe procedure, with a low risk of complications and morbidity.

Optimizing the quality of referral letters could be the first step to a correct clinical approach for patients. Referral letters should be legible and contain the necessary information to avoid delaying the patient's diagnosis and treatment. However, to date, few studies have been conducted on how referrals are performed in Brazil. Knowledge regarding the quality of referral letters can provide information to better guide health care professionals. This study was aimed at analyzing all referrals received by a single oral medicine service in Brazil. Referral letters were classified into poor, regular, good, and excellent based on key items concerning the primary morphology of the lesion, location, diagnostic hypothesis, symptomatology, time of evolution, consistency, size, and limits. A total of 500 referral letters were evaluated, including 271 (54.2%) from a private service and 229 (45.8%) from a public service. Dentists and physicians had written 475 (95%) and 25 (5%) referral letters, respectively. Among the 500 referrals analyzed in this study, the number of regular, poor, good, and excellent referrals was 236 (47.2%), 203 (40.6%), 58 (11.6%), and one (0.6%), respectively, showing a lack of important clinical information in referrals.

Background/purpose: The aim of the study was to evaluate the postoperative quality of life (QoL) of patients who underwent minimally invasive repair of pectus excavatum (MIRPE) with a newly designed bar and bar stabilizers., Methods: We conducted a prospective randomized study in which patients were operated either with standard perpendicular stabilizers (control group) or with the newly designed oblique stabilizers (intervention group). All patients were evaluated 6 months after the operation with the Pectus Excavatum Evaluation Questionnaire (PEEQ)., Results: There were 16 patients in the control group and 14 in the intervention group. Mean age was 17 (SD: 3.3, range 14-27) years. There were no demographic differences between groups. Two patients in the control group and one in the intervention group were repaired with two bars instead of one. There was one reoperation in each group. There was a significant difference between the pre- and postoperative scores, in both groups, in the patient body image domain (control group: 9.5 to 3; p < 0.01; intervention group 10 to 3; p < 0.01), as well as in the psychosocial domain (control group: 13.5 to 24, p < 0.01; intervention group: 15 to 24, p < 0.01). With regards to the patients' perception of physical difficulties before and after MIRPE, the difference between pre- and postoperative scores was greater in the intervention group (8 to 12, p < 0.01) than in the control group (10 to 11, p = 0.04). The mean length of stay was 4.5 and 5 days in the intervention group and the control group, respectively., Conclusion: Our study showed that patients who underwent MIRPE with the newly designed bars and stabilizers had non-inferior outcomes than patients reported in the literature who underwent MIRPE with standard bars and stabilizers. We found slightly better outcomes in patients in the intervention group compared to the control group, but larger studies will be needed to confirm if those differences are statistically significant., Level of Evidence: II., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases.

Objective: To evaluate the evolution of clinical and epidemiological data, as well as data related to diagnosis, staging, treatment, and survival, among patients undergoing curative surgery for lung cancer at a tertiary referral center in the city of São Paulo, Brazil., Methods: This was a retrospective study of cases in the International Association for the Study of Lung Cancer database. We selected only cases of patients undergoing curative surgery between January of 2011 and April of 2018. We determined overall and disease-free survival at 36 months and compared the data between two periods (2011-2014 and 2015-2018)., Results: Comparing the two periods (N = 437 cases), we observed trends toward increases in the number of female patients, as well as in the proportions of former smokers (44.09% vs. 53.59%), of patients diagnosed with adenocarcinoma (52.21% vs. 59.72%), and of patients diagnosed at an earlier pathological stage, together with a decrease in 30-day mortality (4.05% vs. 2.39%). There were significant increases in the proportions of cases diagnosed at an earlier clinical stage (p = 0.002) or incidentally (p = 0.003). Although lobectomy was the main surgical technique employed, there was a proportional increase in segmentectomies (2.67% vs. 7.11%; p = 0.026). Overall and disease-free survival rates were 79.4% (95% CI: 74.0-83.9%) and 75.1% (95% CI: 69.1-80.1%), respectively. The difference in overall survival between the periods lost statistical significance when adjusted for pathological stage, the only factor that affected survival (log-rank: p = 0.038 to p = 0.079)., Conclusions: The clinical and epidemiological evolution presented in this study corroborates global trends. The decrease in 30-day mortality was probably due to better patient selection and improved surgical techniques.

6-Phosphofructokinase-1-kinase (PFK) tetramers catalyse the phosphorylation of fructose 6-phosphate (F6P) to fructose 1,6-bisphosphate (F16BP). Vertebrates have three PFK isoforms (PFK-M, PFK-L, and PFK-P). This study is the first to compare the kinetics, structures, and transcript levels of recombinant human PFK isoforms. Under the conditions tested PFK-M has the highest affinities for F6P and ATP (K0.5ATP 152 µM; K0.5F6P 147 µM), PFK-P the lowest affinities (K0.5ATP 276 µM; K0.5F6P 1333 µM), and PFK-L demonstrates a mixed picture of high ATP affinity and low F6P affinity (K0.5ATP 160 µM; K0.5F6P 1360 µM). PFK-M is more resistant to ATP inhibition compared with PFK-L and PFK-P (respectively, 23%, 31%, 50% decreases in specificity constants). GTP is an alternate phospho donor. Interface 2, which regulates the inactive dimer to active tetramer equilibrium, differs between isoforms, resulting in varying tetrameric stability. Under the conditions tested PFK-M is less sensitive to fructose 2,6-bisphosphate (F26BP) allosteric modulation than PFK-L or PFK-P (allosteric constants [K0.5ATP+F26BP/K0.5ATP] 1.10, 0.92, 0.54, respectively). Structural analysis of two allosteric sites reveals one may be specialised for AMP/ADP and the other for smaller/flexible regulators (citrate or phosphoenolpyruvate). Correlations between PFK-L and PFK-P transcript levels indicate that simultaneous expression may expand metabolic capacity for F16BP production whilst preserving regulatory capabilities. Analysis of cancer samples reveals intriguing parallels between PFK-P and PKM2 (pyruvate kinase M2), and simultaneous increases in PFK-P and PFKFB3 (responsible for F26BP production) transcript levels, suggesting prioritisation of metabolic flexibility in cancers. Our results describe the kinetic and transcript level differences between the three PFK isoforms, explaining how each isoform may be optimised for distinct roles., (© 2020 The Author(s).)

Background : The impact of the coronavirus disease 2019 (COVID-19) pandemic on people with multiple sclerosis (MS) is a major current concern, in particular the risk of death. Here we describe the impact of the first wave of COVID-19 infections (Mar 2020-July 2020) on the Scottish MS Register (SMSR) population, a cohort of 4702 individuals with MS, all newly diagnosed in the past decade. Methods : We established a clinician alert system, linking the SMSR with the Electronic Communication of Surveillance in Scotland (ECOSS). This allows identification of patients within this cohort who had a positive SARS-CoV-2 PCR test. The SMSR was also linked to death records from National Records Scotland. Results : Of 4702 people with MS, 246 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR tests were performed, of which 17 were positive. The proportion of positive tests were similar to the general Scotland population (Observed PCR confirmed cases = 17, expected = 17.5, O/E = 0.97, 95% CI: 0.60 - 1.56, p =.90). Between 1 st March - 31 st July 2020 12 individuals on the SMSR died, 5 of which were linked to COVID-19 (1 PCR confirmed, 4 clinical diagnoses without PCR confirmation). This number of COVID-19-related deaths was higher than expected (observed deaths = 5, expected deaths = 1.2, O/E = 4.03, 95% CI = 1.48 - 8.94, p =.01). All COVID-19-related deaths in the SMSR occurred in individuals with advanced disability (Expanded Disability Status Scale ≥7), and no deaths occurred in patients receiving disease modifying therapy (DMT) therapies. Conclusion : In this nationally comprehensive cohort of MS patients diagnosed in Scotland within the past 10 years, we observed similar rates of PCR-confirmed SARS-CoV-2 infection compared to the general Scottish population, but a small number of excess COVID-19 related deaths. These deaths occurred in individuals with advanced disability who were not receiving DMTs., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Fernandes PM et al.)

Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.

Objective: To evaluate the contribution that unilateral thoracic sympathectomy in dominant side or two-stage bilateral thoracic sympathectomy can have as strategies to reduce the incidence of compensatory sweating after sympathectomy for palmar hyperhidrosis., Methods: This is a prospective, controlled, randomized multicenter trial of 200 participants with palmar hyperhidrosis, which will be randomized into two arms: (a) one-stage bilateral thoracic sympathectomy (control arm); or (b) unilateral thoracic sympathectomy in dominant side (intervention arm). At six months the participants submitted to unilateral procedure can make the contralateral surgery if they wanted it, creating a third group called two-stage bilateral sympathectomy. Participants will be evaluated for the degree of sweating by the Hyperhidrosis Disease Severity Scale (HDSS) and of quality of life questionnaires., Results: 96 participants out of the 200 proposed have been included so far, with 48 participants randomized to each arm. From the sample 61 (63.5%) are female, with a mean age of 24 (20-32) years. There were exclusive palmar hiperhydrosis in 14 cases (14.5%), palmar and plantar hyperhidrosis in 36 (37.5%) cases, palmar and axillar hyperhidrosis in 12 (12,5%) cases and palmar-axillary-plantar hyperhidrosis in 34 (35,4%) cases. The age at the beginning of the disease was childhood (78%), with mean of time of disease 15 (11-22) years., Conclusions: If one or both hypothesis: (a) unilateral sympathectomy in dominant hand is a satisfactory treatment; b) two-stage bilateral sympathectomy causes less compensatory sweating than in one stage are confirmed there is a chance that surgical therapy for palmar hyperhidrosis can be changed for better., Competing Interests: The authors declared no conflict of interest., (© 2020 Published by Elsevier Inc.)

Progressive multifocal leukoencephalopathy is a rare demyelinating disorder of the CNS, caused by John Cunningham virus, that occurs in those with impaired immune systems. Existing treatment options are ineffective or unproven. This article reviews research into novel therapies: immune checkpoint-blocking antibodies (nivolumab and pembrolizumab), allogenic BK virus-specific T cell treatment and filgrastim. Results for these therapies in small clinical trials are promising, but further research is required to assess efficacy fully.

Background: Malignant pleural effusion (MPE) is an important sign of advanced disease in metastatic cancer. Pleurodesis is one option to treat recurrent MPE. The Inflammatory response after pleurodesis may lead to important adverse events (AE) in a set of very ill patients., Methods: Retrospective analysis of patients submitted to pleurodesis (2009-2013). Clinical and laboratory data were collected. We compare the values in the day of pleurodesis, 2 nd , 5 th and 10 th days after., Results: One hundred fourteen patients were undergone to pleurodesis with silver nitrate (46%), iodine (52%) and talc (2%). Female was the most frequent (86%) and the breast cancer was the most common primary site. The most frequent adverse event was low hemoglobin account (37), followed by pain (31). 68% of patients presented AEs and 28% had at least one AE with grade 3 or higher. The most altered was CRP that peaked in the 5 th day after pleurodesis. Changes in CRP curve were less severe with the use of iodine when compared with the other two agents., Conclusions: Pleurodesis leads to important systemic inflammatory response detected by different serum markers. The occurrence of adverse events in this set of patients was great number of events with being marked as grade 3 or higher., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-19-3850). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Trypanosomatids possess glycosome organelles that contain much of the glycolytic machinery, including phosphofructokinase (PFK). We present kinetic and structural data for PFK from three human pathogenic trypanosomatids, illustrating intriguing differences that may reflect evolutionary adaptations to differing ecological niches. The activity of Leishmania PFK - to a much larger extent than Trypanosoma PFK - is reliant on AMP for activity regulation, with 1 mm AMP increasing the L. infantum PFK (LiPFK) kcat/K 0.5 F6P value by 10-fold, compared to only a 1.3- and 1.4-fold increase for T. cruzi and T. brucei PFK, respectively. We also show that Leishmania PFK melts at a significantly lower (> 15 °C) temperature than Trypanosoma PFKs and that addition of either AMP or ATP results in a marked stabilization of the protein. Sequence comparisons of Trypanosoma spp. and Leishmania spp. show that divergence of the two genera involved amino acid substitutions that occur in the enzyme's 'reaching arms' and 'embracing arms' that determine tetramer stability. The dramatic effects of AMP on Leishmania activity compared with the Trypanosoma PFKs may be explained by differences between the T-to-R equilibria for the two families, with the low-melting Leishmania PFK favouring the flexible inactive T-state in the absence of AMP. Sequence comparisons along with the enzymatic and structural data presented here also suggest there was a loss of AMP-dependent regulation in Trypanosoma species rather than gain of this characteristic in Leishmania species and that AMP acts as a key regulator in Leishmania governing the balance between glycolysis and gluconeogenesis., (© 2019 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The COVID-19 Pandemic has resulted in a high number of hospital admissions and some of those patients need ventilatory support in intensive care units. The viral pneumonia secondary to Sars-cov-2 infection may lead to acute respiratory distress syndrome (ARDS) and longer mechanical ventilation needs, resulting in a higher demand for tracheostomies. Due to the high aerosolization potential of such procedure, and the associated risks of staff and envoirenment contamination, it is necesseray to develop a specific standardization of the of the whole process involving tracheostomies. This manuscript aims to demonstrate the main steps of the standardization created by a tracheostomy team in a tertiary hospital dedicated to providing care for patients with COVID-19.

Kartagener syndrome (KS) is a rare congenital disorder related to bronchiectasis, chronic sinusitis, and situs inversus, predisposing patients to recurrent respiratory infections that can evolve to end-stage lung disease; lung transplantation (LTx) is one of the therapeutic options. This study highlights some concerns in this group of patients, mainly related to the difficulty of performing the transplantation in recipients with suppurative disease and situs inversus. We conducted a retrospective analysis of all KS patients who underwent LTx at 2 national reference centers by the same LTx team. During 29 years of analysis, we performed 12 cases of bilateral sequential LTx in KS patients, representing 2.4% of all Ltx that we performed. Special perioperative care is needed, including vascular access sites and lung isolation techniques; operative concerns include the arteriotomy and bronchotomy during the back table preparation of the graft and concern about the length of the arterial and bronchial anastomosis. We found a higher incidence of bronchial complications is this group that had not been previously reported. Bilateral sequential orthotopic LTx is feasible in this group of patients, and more studies are needed to understand possible reasons for the apparent higher incidence of bronchial complications., (Copyright © 2020. Published by Elsevier Inc.)

Background: The aim of this work was to evaluate the microscopic characteristics through polarized light microscopy, scanning electron microscopy and the mineral content of circumpulpal dentin of irradiated (IT) and non-irradiated teeth (NIT), with deep caries that reached the root canal., Material and Methods: A total of 25 IT were analyzed macroscopically, and radiographed. 5 NIT were used as controls. Two 100-μm-thick sections, per specimen, were evaluated in a polarized light microscopy and a scanning electron microscope. Demographics and clinical data were collected., Results: The results did not demonstrate distinct morphology of the IT compared with NIT. Mineral content values by weight percentage of Ca and P were also similar, corresponding to 66.65% and 33.21% in the IT and 66.60% and 33.29% in the NIT. The Ca/P ratio did not show statistical differences between groups being respectively 2.74 and 2.72, in the IT and NIT ( p > 0.05)., Conclusions: Radiotherapy does not change morphology and mineral content of circumpulpal dentin in IT. Key words: Root canal, radiation-related caries, polarization microscopy, scanning electron microscopy, radiotherapy, oral neoplasms, dentin., Competing Interests: Conflicts of interest The authors deny any conflict of interest., (Copyright: © 2020 Medicina Oral S.L.)

Objective: To report initial experience from the use of extracorporeal membrane oxygenation (ECMO) in patients who received lung transplantation., Methods: Retrospective study of a single tertiary center in the Brazilian state of São Paulo, a national reference in lung transplantation, based on the prospective collection of data from electronic medical records. The period analyzed extended from January 2009 (beginning of the program) until December 2018., Results: A total of 75 lung transplants were performed, with ECMO used in 8 (10.7%) cases. Of the patients, 4 (50%) were female. The mean age was 46.4±14.3 years. The causes of the end-stage lung disease that led to transplantation were pulmonary arterial hypertension in 3 (37.5%) patients, bronchiectasis in 2 (25%) patients, pulmonary fibrosis in 2 (25%) patients, and pulmonary emphysema in 1 (12.5%) patient. In our series, 7 (87.5%) cases were sequential bilateral transplantations. Prioritization was necessary in 4 (50%) patients, and in 1 patient, ECMO was used as a bridge to transplantation. The ECMO route was central in 4 (50%), peripheral venovenous in 2 (25%) and peripheral venoarterial in 2 (25%) patients. The mean length of the intensive care unit (ICU) stay was 14±7.5 days and of the hospital stay was 34.1±34.2 days. The mean ECMO duration was 9.3±6.6 days with a 50% decannulation rate. Three patients were discharged (37.5%)., Conclusion: Lung transplantation requires complex treatment, and ECMO has allowed extending the indications for transplantation and provided adjuvant support in the clinical management of these patients.

Benign airway stenosis is a multifactorial and heterogeneous disease often occurring after tracheal intubation. Despite the frequent finding of pathological gastroesophageal reflux (GER) in benign tracheal stenosis, the cause-and-effect relationship between these two entities and its impact on the outcome of the stenosis itself have not been established. The altered ventilatory dynamics caused by an increased thoracoabdominal pressure gradient in such patients has been proposed as a central cause. The presence of GER in a setting of microaspiration can also induce changes in the local collagen proliferation response, as well as in the local microbiome of the tracheal stenosis site, which may potentially cause and enhance the harm imposed to the already diseased tracheal wall. Diagnosis of GER remains underestimated in the general population, thus making its accurate detection and treatment in central airway stenosis a matter of investigation. The high prevalence of GER in tracheal stenosis patients often occurs in the absence of typical upper digestive signs and symptoms, therefore requiring an objective assessment using a 24-hour ambulatory esophageal pH/impedance study that has shown abnormal results in more than half the patients. The impact of the treatment of GER in patients with benign tracheal has been scarcely reported. Our group showed recently that the surgical control of GER through laparoscopic fundoplication in selected patients with tracheal stenosis can improve substantially the chance of resolution of the tracheal stenosis as opposed to the medical management with high dose proton pump inhibitors. This chapter describes the impact of GER in the pathogenesis of tracheal stenosis with a focus on its mechanisms, diagnosis and treatment strategy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2020.03.24). The series “Recent Developments in Benign Tracheal Stenosis” was commissioned by the editorial office without any funding or sponsorship. BJB and PFGC served as the unpaid Guest Editors of the series. The authors have no other conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Objective: To describe the morbidity, mortality, and rate of complete resection associated with robotic surgery for the treatment of non-small cell lung cancer in Brazil, as well as to report the rates of overall survival and disease-free survival in patients so treated., Methods: This was a retrospective study of patients diagnosed with non-small cell lung carcinoma and undergoing resection by robotic surgery at one of six hospitals in Brazil between February of 2015 and July of 2018. Data were collected retrospectively from the electronic medical records., Results: A total of 154 patients were included. The mean age was 65 ± 9.5 years (range, 30-85 years). The main histological diagnosis was adenocarcinoma, which was identified in 128 patients (81.5%), followed by epidermoid carcinoma, identified in 14 (9.0%). Lobectomy was performed in 133 patients (86.3%), and segmentectomy was performed in 21 (13.7%). The mean operative time was 209 ± 80 min. Postoperative complications occurred in 32 patients (20.4%). The main complication was air leak, which occurred in 15 patients (9.5%). The median (interquartile range) values for hospital stay and drainage time were 4 days (3-6 days) and 2 days (2-4 days), respectively. There was one death in the immediate postoperative period (30-day mortality rate, 0.5%). The mean follow-up period was 326 ± 274 days (range, 3-1,110 days). Complete resection was achieved in 97.4% of the cases. Overall mortality was 1.5% (3 deaths), and overall survival was 97.5%., Conclusions: Robotic pulmonary resection proved to be a safe treatment for lung cancer. Longer follow-up periods are required in order to assess long-term survival.

Objective: To evaluate the results of resection of tumors of the thymus by robotic thoracic surgery, analyzing the extent of resection, postoperative complications, time of surgery, and length of stay., Methods: Retrospective study from a database involving patients diagnosed with a tumor of the thymus and undergoing robotic thoracic surgery at one of seven hospitals in Brazil between October of 2015 and June of 2018., Results: During the study period, there were 18 cases of resection of tumors of the thymus: thymoma, in 12; carcinoma, in 2; and carcinoid tumor, in 1; high-grade sarcoma, in 1; teratoma, in 1; and thymolipoma, in 1. The mean lesion size was 60.1 ± 32.0 mm. Tumors of the thymus were resected with tumor-free margins in 17 cases. The median (interquartile range) for pleural drain time and hospital stay, in days, was 1 (1-3) and 2 (2-4), respectively. There was no need for surgical conversion, and there were no major complications., Conclusions: Robotic thoracic surgery for resection of tumors of the thymus has been shown to be feasible and safe, with a low risk of complications and with postoperative outcomes comparable to those of other techniques.

Objective: This study focuses on the impact of antireflux surgery in the outcome of tracheal stenosis., Methods: We performed a retrospective study including patients with benign tracheal stenosis who underwent esophageal manometry and dual-probe 24-hour ambulatory esophageal pH study. Patients with an abnormal pH study were managed with laparoscopic modified Nissen fundoplication or medically (omeprazole 80 mg/d, orally). Patients with normal pH study results were observed. After a 24-month follow-up, the outcome was considered satisfactory if tracheal stenosis could be managed by resection and there was no need for further dilatation or definitive decannulation. The management groups were compared using propensity score matching., Results: A total of 175 patients were included. Abnormal pH study results were found in 74 patients (42.3%), and 12.6% of patients had typical gastroesophageal reflux symptoms. Follow-up was completed in 124 patients (20 had fundoplication, 32 received omeprazole, and 72 were observed). After propensity score matching, the outcome of tracheal stenosis in the fundoplication group was similar to that of the observation group (odds ratio, 1; P = .99) and better than that of the omeprazole group (odds ratio, 5.31; P = .03). The observation (no gastroesophageal reflux) group had a better outcome of stenosis than those treated with omeprazole (odds ratio, 3.54; P = .02)., Conclusions: The outcome of the airway stenosis was superior after laparoscopic fundoplication compared with medical treatment with omeprazole and was similar to the outcome of patients without gastroesophageal reflux. A prospective randomized trial is warranted., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: In the last decade, robotic video-assisted thoracic surgery (R-VATS) has grown significantly and consolidated as an alternative to video-assisted thoracic surgery. The objective of this study is to present the implementation as well as the experience with R-VATS accumulated by 2 Brazilian groups. We also compared the outcomes of procedures performed during the learning curve and after a more mature experience., Methods: Retrospective cohort study included all R-VATS procedures performed since April 2015 until April 2018. We describe the process of implantation of robotic surgery, highlighting the peculiarities and difficulties found in a developing country. Moreover, we reported our descriptive results and compared the first 60 patients to the subsequent cases., Results: Two hundred and five patients included 101 females/104 males. Mean age was 61.7 years. There were hundred and sixty-four pulmonary resections, 39 resections of mediastinal lesions, 1 diaphragmatic plication, and 1 resection of a hilar tumor. Median operative times were 205 min for lung resections and 129 min for mediastinal. There was no conversion to VATS or thoracotomy or major intraoperative complications. Median length of stay was 3 days for pulmonary resections and 1 day for mediastinal. Postoperative complications occurred in 35 cases (17.0%)-prolonged air leak was the most common (17 cases). One fatality occurred in an elderly patient with pneumonia and sepsis (0.4%). Comparison of the first 60 patients (learning curve) with subsequent 145 patients (consolidated experience) showed significant differences in surgical and ICU time, both favoring consolidated experience., Conclusions: Our results were comparable to the literature. Robotic thoracic surgery can be safely and successfully implemented in tertiary hospitals in emerging countries provided that all stakeholders are involved and compromised with the implementation process.

Objective: to report our initial experience with pulmonary robotic segmentectomy, describing the surgical technique, the preferred positioning of portals, initial results and outcomes., Methods: we collected data, from a prospective robotic surgery database, on patients undergoing robotic segmentectomy between January 2017 and December 2018. All patients had lung cancer, primary or secondary, or benign diseases, and were operated on with the Da Vinci system, by the three portals technique plus one utilitarian incision of 3cm. We dissected the hilar structures individually and performed the ligatures of the arterial and venous branches, of the segmental bronchi, as well as a parenchymal transection, with endoscopic staplers. We carried out systematic dissection of mediastinal lymph nodes for non-small cell lung cancer (NSCLC) cases., Results: forty-nine patients, of whom 33 were women, underwent robotic segmentectomy. The average age was of 68 years. Most patients had NSCLC (n=34), followed by metastatic disease (n=11) and benign disease (n=4). There was no conversion to laparoscopic or open surgery, or to lobectomy. The median total operative time was 160 minutes, and the median console time, 117 minutes. Postoperative complications occurred in nine patients (18.3%), of whom seven (14.2%) had prolonged hospitalization (>7 days) due to persistent air fistula (n=4; 8.1%) or abdominal complications (n=2.4%)., Conclusion: robotic segmentectomy is a safe and viable procedure, offering a short period of hospitalization and low morbidity.

To evaluate the feasibility of a 980-nm contact diode laser (CDL) as a method for creating a posterior laryngofissure in live pigs. Twenty-eight Landrace pigs (15-20 kg) were anesthetized, intubated, ventilated, and submitted to a cervical tracheostomy. An anterior and posterior midline longitudinal laryngofissure incision was created according to randomization-control (n = 4), posterior laryngofissure with a scalpel blade; electrocautery (n = 12), posterior laryngofissure by electrocautery (10, 15, 20, 25 W powers); CDL (n = 12), posterior laryngofissure by the CDL (10, 15, 20, 25 W peak powers in pulsed mode). Larynx and proximal trachea were excised, prepared for histopathology, and digital morphometric analysis. Measurements in and within each group were analyzed (Kruskal-Wallis and Dunn test) with a level of significance of p < 0.05. Incision width was not different between the groups, as well as in the powers used in CDL (p = 0.161) and electrocautery group (p = 0.319). The depth of the incisions was smaller in the Laser group compared to control (p = 0.007), and in the electrocautery compared to control (p = 0.026). Incision area was smaller in CDL compared with the control (p = 0.027), and not different between laser and electrocautery groups (p = 0.199). The lateral thermal damage produced by electrocautery was the largest, with a significant difference between laser and electrocautery (p = 0.018), and between electrocautery and control (p = 0.004), whereas the comparison between laser and control showed no significant differences (p = 0.588). The posterior laryngofissure incision using a 980-nm CDL is feasible resulting in smaller incisional area and less lateral thermal damage.

Objective: To assess the feasibility and impact of ex vivo lung perfusion with hyperoncotic solution (Steen Solution™) in the utilization of these organs in Brazil., Methods: In this prospective study, we subjected five lungs considered to be high risk for transplantation to 4 hours of ex vivo lung perfusion, with evaluation of oxygenation capacity. High-risk donor lungs were defined by specific criteria, including inflammatory infiltrates, pulmonary edema and partial pressure of arterial oxygen less than 300mmHg (inspired oxygen fraction of 100%)., Results: During reperfusion, the mean partial pressure of arterial oxygen (inspired oxygen fraction of 100%) of the lungs did not change significantly (p=0.315). In the first hour, the mean partial pressure of arterial oxygen was 302.7mmHg (±127.66mmHg); in the second hour, 214.2mmHg (±94.12mmHg); in the third hour, 214.4mmHg (±99.70mmHg); and in the fourth hour, 217.7mmHg (±73.93mmHg). Plasma levels of lactate and glucose remained stable during perfusion, with no statistical difference between the moments studied (p=0.216)., Conclusion: Ex vivo lung perfusion was reproduced in our center and ensured the preservation of lungs during the study period, which was 4 hours. The technique did not provide enough improvement for indicating organs for transplantation; therefore, it did not impact on use of these organs.

Introduction/objective: Tracheal resection with primary reconstruction is the definitive treatment for many tracheal benign and malignant diseases. When primary resection is not deemed feasible as a result of the length of the stenosis, airway transplantation may become a solution. Tissue engineering offers an alternative way for creating tracheal substitutes. The development of tracheal allograft transplantation includes the decellularized tracheal scaffolds made of extracellular matrix that are seeded with the receptor's cells. Many protocols are used to obtain a decellularized scaffold. Most of them consist of cyclical physical-chemical steps with enzymes. This study proposes a protocol for decellularization based only in physical-chemical steps., Methods: Decellularization of pig tracheal segments was carried out using a standardized protocol consisting of freezing and thawing, 10 cycles of agitation, exposure to sodium deoxycholate, and washing. The degree of decellularization was determined by quantifying residual DNA. We also analyzed the morphology under hematoxylin and eosin staining., Results: Fourteen porcine tracheal segments were decellularized. All scaffolds obtained showed less than 2% of residual DNA (mean 20 ± 8 ng/mg) when compared to the fresh samples (mean 850 ± 123 ng/mg), P = .001. Morphological analysis showed that the epithelium and mixed glands were completely removed. It was possible to identify residual nuclei inside the cartilaginous rings (73.7 ± 12 × 26 ± 8 nuclei/field, P < .001)., Conclusion: The protocol tested was able to provide effective decellularization of porcine tracheas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Eucalypts, especially blue gum (Eucalyptus globulus), have been extensively planted in Portugal and nowadays dominate most of its forest landscapes. Large-scale forestation programs can intensify fire activity, and blue gum plantations are often viewed as highly flammable due to the nature and structure of the fuel complex. The role of eucalypt plantations in the fire regime of Mediterranean climate regions is increasingly debated following the recent catastrophic wildfires in Portugal and elsewhere. In this study we examined the effects of eucalypt forestation on burned area (BA), fire size, and fire severity in Portugal. This was based on fire and vegetation mapping and statistics, fire weather data, satellite imagery, and national forest inventory data. Eucalypt BA comprised an average of 12.5% of total BA (1980-2017) and did not increase over time and with eucalypt expansion. Eucalypt metrics did not explain interannual BA variability after accounting for the effects of other variables. Forest fires started within eucalypt stands were the least likely to become large, and large fire size was irresponsive to forest composition. Likewise, forest type was a generally minor influence in mega-fire severity and accounted for just 1.4-8.6% of surface fuel-hazard metrics variation. In general, large-scale conversion of maritime pine to eucalypt stands (1970-2015) implied lower fuel accumulation. Fire activity results are consistent with fuel hazard results and express trade-offs between short-rotation forestry and fire behaviour in blue gum stands, with high spotting potential versus modest crown fire likelihood. We found no support for the contention of a modified fire regime as a result of eucalypt forestation in Portugal, but the rising undermanaged and abandoned blue gum estate, especially after large-fire seasons, is a concern for the future. However, it remains to be determined whether post-fire eucalypt regrowth is a higher fire threat than native vegetation in the same context., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Minimally invasive repair of pectus excavatum (MIRPE) is a surgical treatment for PE. During the procedure, a specialized introducer is used to tunnel across the mediastinum for thoracoscopic insertion of a metal bar. There have been reported cases of cardiac perforation during this risky step. The large introducer can be a dangerous lever in unskilled hands. We set out to determine the safety and feasibility of using regular instruments (i.e., not relying on special devices or tools) to create the retrosternal tunnel during MIRPE., Methods: This was a preliminary study of MIRPE with regular instruments (MIRPERI), involving 28 patients with PE. We recorded basic patient demographics, chest measurements, and surgical details, as well as intraoperative and postoperative complications., Results: Patients undergoing MIRPERI had Haller index values ranging from 2.58 to 5.56. No intraoperative complications occurred. Postoperative complications included nausea/vomiting in 8 patients, pruritus in 2, and dizziness in 2, as well as atelectasis, pneumothorax with thoracic drainage, pleural effusion, and dyspnea in 1 patient each., Conclusions: In this preliminary study, the rate of complications associated with MIRPERI was comparable to that reported in the literature for MIRPE. The MIRPERI approach has the potential to improve the safety of PE repair, particularly for surgeons that do not have access to certain special instruments or have not been trained in their use.

Rhabdomyolysis is the combination of symptoms (myalgia, weakness and muscle swelling) and a substantial rise in serum creatine kinase (CK) >50 000 IU/L; there are many causes, but here we specifically address exertional rhabdomyolysis. The consequences of this condition can be severe, including acute kidney injury and requirement for higher level care with organ support. Most patients have 'physiological' exertional rhabdomyolysis with no underlying disease; they do not need investigation and should be advised to return to normal activities in a graded fashion. Rarely, exertional rhabdomyolysis may be the initial presentation of underlying muscle disease, and we review how to identify this much smaller group of patients, who do require investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)