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1.
Eur Respir J ; 63(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38806203

RESUMO

BACKGROUND: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.


Assuntos
Pneumotórax , Humanos , Pneumotórax/terapia , Adulto , Pleurodese , Medicina Baseada em Evidências , Tubos Torácicos , Sociedades Médicas , Recidiva , Europa (Continente)
2.
Langenbecks Arch Surg ; 409(1): 137, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653917

RESUMO

PURPOSE: Minimal-invasive liver surgery (MILS) reduces surgical trauma and is associated with fewer postoperative complications. To amplify these benefits, perioperative multimodal concepts like Enhanced Recovery after Surgery (ERAS), can play a crucial role. We aimed to evaluate the cost-effectiveness for MILS in an ERAS program, considering the necessary additional workforce and associated expenses. METHODS: A prospective observational study comparing surgical approach in patients within an ERAS program compared to standard care from 2018-2022 at the Charité - Universitätsmedizin Berlin. Cost data were provided by the medical controlling office. ERAS items were applied according to the ERAS society recommendations. RESULTS: 537 patients underwent liver surgery (46% laparoscopic, 26% robotic assisted, 28% open surgery) and 487 were managed by the ERAS protocol. Implementation of ERAS reduced overall postoperative complications in the MILS group (18% vs. 32%, p = 0.048). Complications greater than Clavien-Dindo grade II incurred the highest costs (€ 31,093) compared to minor (€ 17,510) and no complications (€13,893; p < 0.001). In the event of major complications, profit margins were reduced by a median of € 6,640. CONCLUSIONS: Embracing the ERAS society recommendations in liver surgery leads to a significant reduction of complications. This outcome justifies the higher cost associated with a well-structured ERAS protocol, as it effectively offsets the expenses of complications.


Assuntos
Análise Custo-Benefício , Recuperação Pós-Cirúrgica Melhorada , Hepatectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias , Humanos , Estudos Prospectivos , Masculino , Feminino , Hepatectomia/economia , Hepatectomia/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/prevenção & controle , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos/economia , Laparoscopia/economia , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/efeitos adversos
3.
Zentralbl Chir ; 2024 Apr 11.
Artigo em Alemão | MEDLINE | ID: mdl-38604234

RESUMO

This manuscript provides an overview of the principles and requirements for implementing the ERAS program in thoracic surgery.The ERAS program optimises perioperative management of elective lung resection procedures and is based on the ERAS Guidelines for Thoracic Surgery of the ERAS Society. The clinical measures are described as in the current literature, with a focus on postoperative outcome. There are currently 45 enhanced recovery items covering four perioperative phases: from the prehospital admission phase (patient education, screening and treatment of potential risk factors such as anaemia, malnutrition, cessation of nicotine or alcohol abuse, prehabilitation, carbohydrate loading) to the immediate preoperative phase (shortened fasting period, non-sedating premedication, prophylaxis of PONV and thromboembolic complications), the intraoperative measures (antibiotic prophylaxis, standardised anaesthesia, normothermia, targeted fluid therapy, minimally invasive surgery, avoidance of catheters and probes) through to the postoperative measures (early mobilisation, early nutrition, removal of a urinary catheter, hyperglycaemia control). Most of these measures are based on scientific studies, with a high level of evidence and aim to reduce general postoperative complications.The ERAS program is an optimised perioperative treatment approach aiming to improve the postoperative recovery in patients after elective lung resection by reducing the overall complication rates and overall morbidity.

4.
Eur J Nucl Med Mol Imaging ; 50(7): 2140-2151, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36820890

RESUMO

BACKGROUND: In patients with non-small cell lung cancer (NSCLC), accuracy of [18F]FDG-PET/CT for pretherapeutic lymph node (LN) staging is limited by false positive findings. Our aim was to evaluate machine learning with routinely obtainable variables to improve accuracy over standard visual image assessment. METHODS: Monocentric retrospective analysis of pretherapeutic [18F]FDG-PET/CT in 491 consecutive patients with NSCLC using an analog PET/CT scanner (training + test cohort, n = 385) or digital scanner (validation, n = 106). Forty clinical variables, tumor characteristics, and image variables (e.g., primary tumor and LN SUVmax and size) were collected. Different combinations of machine learning methods for feature selection and classification of N0/1 vs. N2/3 disease were compared. Ten-fold nested cross-validation was used to derive the mean area under the ROC curve of the ten test folds ("test AUC") and AUC in the validation cohort. Reference standard was the final N stage from interdisciplinary consensus (histological results for N2/3 LNs in 96%). RESULTS: N2/3 disease was present in 190 patients (39%; training + test, 37%; validation, 46%; p = 0.09). A gradient boosting classifier (GBM) with 10 features was selected as the final model based on test AUC of 0.91 (95% confidence interval, 0.87-0.94). Validation AUC was 0.94 (0.89-0.98). At a target sensitivity of approx. 90%, test/validation accuracy of the GBM was 0.78/0.87. This was significantly higher than the accuracy based on "mediastinal LN uptake > mediastinum" (0.7/0.75; each p < 0.05) or combined PET/CT criteria (PET positive and/or LN short axis diameter > 10 mm; 0.68/0.75; each p < 0.001). Harmonization of PET images between the two scanners affected SUVmax and visual assessment of the LNs but did not diminish the AUC of the GBM. CONCLUSIONS: A machine learning model based on routinely available variables from [18F]FDG-PET/CT improved accuracy in mediastinal LN staging compared to established visual assessment criteria. A web application implementing this model was made available.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Mediastino/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Estudos Retrospectivos , Linfonodos/patologia , Estadiamento de Neoplasias
5.
Zentralbl Chir ; 148(1): 93-104, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36822185

RESUMO

Thoracic trauma is a frequent injury pattern with high patient morbidity and mortality. Preclinical and clinical emergency treatment is consented in a national S3-guideline. Following emergency therapy one third of patients may develop lung lacerations, pleural fistulation and persisting pneumothorax. An interdisciplinary working group of the German Society for Thoracic Surgery and the German Society for Traumatology reviewed the published medical literature on treatment of those injuries and assessed the existing evidence according to consensus recommendations. An inconsistent classification of those subsequent lung injuries was found. Evidence for diagnostic and therapeutic recommendations is small.


Assuntos
Fístula , Lacerações , Lesão Pulmonar , Doenças Pleurais , Pneumotórax , Traumatismos Torácicos , Humanos , Pneumotórax/terapia , Pulmão , Traumatismos Torácicos/cirurgia
6.
Zentralbl Chir ; 148(1): 74-84, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36470290

RESUMO

Since the early 1990s, video-assisted thoracoscopy (VATS) has been increasingly established for a variety of indications in the treatment of patients with thoracic trauma. During this time, one premise for the use of thoracoscopy has not changed. Its use is consistently recommended only for trauma patients with stable circulation and respiration. To define the indications of VATS for use in thoracic trauma, the Pulmonary Injury Group - as part of the Working Committee for Thoracic Trauma of the German Society for Thoracic Surgery (DGT) and the German Society for Trauma Surgery (DGU) - has developed treatment recommendations based on a current literature review (based on the PRISMA Checklist/here: MEDLINE via PubMed from 1993 to 2022). In the present study, after reviewing the available literature, the indications for VATS in the care of thoracic trauma were identified, in order to formulate clinical recommendations for the use of VATS in thoracic trauma. The analysis of 1679 references identified a total of 4 randomised controlled trials (RCTs), 4 clinical trials, and 5 meta-analyses or systematic reviews and 39 reviews, which do not allow a higher level of recommendation than consensual recommendations, due to the low evidence of the available literature. Over the past 30 years, stabilisation options in the care of trauma patients have improved significantly, allowing expansion of indications for the use of VATS. Moreover, the recommendation for more than 50 years to thoracotomise trauma patients in case of an initial blood loss ≥ 1500 ml via the inserted chest drainage or in case of continuous blood loss ≥ 250 ml/h over 4 h is now only relative with today's better stabilisation measures. For unstable/non-stabilisable patients with a thoracic injury requiring emergency treatment, thoracotomy remains the method of choice, while VATS is recommended for a wide range of indications in the diagnosis and treatment of stable patients with a penetrating or blunt thoracic trauma. The indications for VATS are persistent haemothorax, treatment of injuries and haemorrhages to the lung, diaphragm, thoracic wall and other organ injuries, and in the secondary phase, treatment of thoracic sequelae of injury (empyema, persistent pulmonary fistula, infected atelectasis, etc.).


Assuntos
Traumatismos Torácicos , Ferimentos não Penetrantes , Humanos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento , Traumatismos Torácicos/cirurgia , Hemotórax/diagnóstico , Toracotomia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/cirurgia , Tórax
7.
Int J Cancer ; 150(12): 2058-2071, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35262195

RESUMO

Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single-cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno- and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single-cell level are yet completely unknown. To study the cellular composition and single-cell gene expression profiles in lung carcinoids, we applied single-cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single-cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in noninflammatory monocyte-derived myeloid cells. Tumor-associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer-associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFß and JAK/STAT signaling. Moreover, single-cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data. Here, we provide first comprehensive insights into the cellular composition and single-cell gene expression profiles in lung carcinoids, demonstrating the noninflammatory and vessel-rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets.


Assuntos
Tumor Carcinoide , Carcinoma Neuroendócrino , Neoplasias Pulmonares , Tumores Neuroendócrinos , Tumor Carcinoide/genética , Tumor Carcinoide/metabolismo , Tumor Carcinoide/patologia , Carcinoma Neuroendócrino/patologia , Células Endoteliais/metabolismo , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Tumores Neuroendócrinos/patologia , Prognóstico , Microambiente Tumoral/genética
8.
Eur Respir J ; 60(6)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35728978

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive. METHODS: Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied to infected human lung explants and adult stem cell derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and Middle East respiratory syndrome coronavirus (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used to validate ex vivo results. RESULTS: We provide evidence that alveolar ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation and virus-induced tissue damage in the human alveolus. Instead, ex vivo infected human lungs and COVID-19 autopsy samples showed that alveolar macrophages were frequently positive for SARS-CoV-2. Single-cell/-nucleus transcriptomics further revealed nonproductive virus uptake and a related inflammatory and anti-viral activation, especially in "inflammatory alveolar macrophages", comparable to those induced by SARS-CoV and MERS-CoV, but different from NL63 or influenza virus infection. CONCLUSIONS: Collectively, our findings indicate that severe lung injury in COVID-19 probably results from a macrophage-triggered immune activation rather than direct viral damage of the alveolar compartment.


Assuntos
COVID-19 , Influenza Humana , Adulto , Humanos , Enzima de Conversão de Angiotensina 2 , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Peptidil Dipeptidase A/metabolismo , SARS-CoV-2 , Tropismo Viral
9.
Zentralbl Chir ; 147(S 01): S21-S28, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-35235992

RESUMO

BACKGROUND, OBJECTIVES: In recent years, ERAS treatment pathways have found their way into many surgical fields, as they reduce complications and accelerate postoperative recovery. For thoracic surgery, the first ERAS guidelines were published by the ERAS Society and the European Society of Thoracic Surgeons (ESTS) in 2019. We have now evaluated how ERAS-items are implemented in clinical practice by using an online survey. MATERIAL AND METHODS: An online survey was conducted from 12/5/2021 until 1/6/2021. The survey consisted of 22 questions focusing on the key elements of an ERAS program according to the published ERAS guidelines. Results were summarised, descriptively analysed and put into context with the current literature. RESULTS: Of 155 thoracic surgeons, 32 responded to the survey. In 28.1% (n = 9) of the hospitals, an ERAS core unit was established, and a database to record the ERAS items existed in 15.6% (n = 5). Only 3.1% (n = 1) kept an ERAS-diary preoperatively. A so-called Carboloading was conducted at 15.6% (n = 5) of surgeons. Standard PONV prophylaxis was administered to 59.4% (n = 19) of the patients. In most cases (84.4%, n = 29), a single drain was inserted into the pleural cavity during anatomic resections. In 3% (n = 1) of the centres two drains, in 12.5% (n = 4) no drainage was placed. The most commonly applied initial suction was -10 cmH2O (75%, n = 24). Suction ≤ 2 cmH2O was used by only two of those interviewed. Drainage removal took place in 50% (n = 16) of cases between the 1st or 2nd POD, in 34.4% of cases (n = 11) between the 3rd and 4th POD and in 9.4% (n = 3) the drain remained longer than the 4th POD. The first postoperative mobilisation took place in 71.9% (n = 23) of the centres on the day of the operation. CONCLUSIONS: The implementation of ERAS guidelines varies in Germany between centres. Certain perioperative processes are covered sufficiently, but the implementation of key features of ERAS is yet to be fully established in clinical practice. The first steps in this direction have already been taken and lay the foundation for cooperation across centres.


Assuntos
Cirurgiões , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Alemanha , Humanos , Tempo de Internação , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Inquéritos e Questionários , Procedimentos Cirúrgicos Torácicos/efeitos adversos
10.
Zentralbl Chir ; 146(1): e1-e6, 2021 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-32785899

RESUMO

BACKGROUND: The new COVID-19 pandemic has an impact on routine thoracic surgery. Various concepts and recommendations are being pursued to protect patients and hospital staff. However, the implementation of these recommendations may depend on the existing infrastructure, local conditions and in-house procedural instructions. MATERIAL AND METHOD: Between 11th May and 26th May 2020, an anonymous online survey on the topic of COVID-19 was conducted among thoracic surgeons in Germany. The survey consisted of 16 questions on the local COVID-19 case numbers, protective measures, procedural instructions and treatment concepts. The results were summarised, descriptively analysed and discussed. RESULTS: The response rate of 42.6% (n = 66), included replies from 23 (34.8%) specialised hospitals, 18 (27.3%) maximum care hospitals and 14 (21.2%) university clinics. COVID-19-positive patients were treated in 65 (99%) clinics and 37.9% of the clinics also performed surgery on COVID-19-positive patients. Nasopharyngeal swabs were the main instrument for COVID-19 patient testing (in 95.4% of the clinics). Test results influenced decisions on treatment in 71.2% of the clinics. In 59.1% of clinics, safety equipment was supplemented with FFP2 masks and eye protection during thoracic surgeries due to the COVID-19 pandemic. DISCUSSION: Almost all thoracic surgeons reported that they had treated patients with COVID-19 and half of them also had performed surgery on COVID-19-positive patients. The applied procedural instructions as well as the effects of COVID-19 on treatment decisions and patient-doctor contact differed between the reporting clinics.


Assuntos
COVID-19 , Cirurgia Torácica , Alemanha , Humanos , Pandemias , SARS-CoV-2
11.
Ann Surg ; 272(6): 950-960, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31800490

RESUMO

OBJECTIVES: PORTAS-3 was designed to compare the frequency of pneumothorax or haemothorax in a primary open versus closed strategy for port implantation. BACKGROUND DATA: The implantation strategy for totally implantable venous access ports with the optimal benefit/risk ratio remains unclear. METHODS: PORTAS-3 was a multicentre, randomized, controlled, parallel-group superiority trial. Adult patients with oncological disease scheduled for elective port implantation were randomized to a primary open or closed strategy. Primary endpoint was the rate of pneumothorax or haemothorax. Assuming a difference of 2.5% between the 2 groups, a sample size of 1154 patients was needed to prove superiority of the open group. A logistic regression model after the intention-to-treat principle was applied for analysis of the primary endpoint. RESULTS: Between November 9, 2014 and September 5, 2016, 1205 patients were randomized. Of these, 1159 (open n = 583; closed n = 576) were finally analyzed. The rate of pneumothorax or haemothorax was significantly reduced with the open strategy [odds ratio 0.27, 95% confidence interval (CI) 0.09-0.88; P = 0.029]. Operation time was shorter for the closed strategy. Primary success rates, tolerability, morbidity, dose rate of radiation, and 30-day mortality did not differ significantly between the groups. CONCLUSION: A primary open strategy by cut-down of the cephalic vein, if necessary enhanced by a modified Seldinger technique, reduces the frequency of pneumothorax or haemothorax after central venous port implantation significantly compared with a closed strategy by primary puncture of the subclavian vein without routine sonographic guidance. Therefore, open surgical cut-down should be the reference standard for port implantation in comparable cohorts. TRIAL REGISTRATION: German Clinical Trials Register DRKS 00004900.


Assuntos
Hemotórax/epidemiologia , Pneumotórax/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Implantação de Prótese/métodos , Dispositivos de Acesso Vascular , Idoso , Antineoplásicos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico
12.
BMC Surg ; 18(1): 90, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373596

RESUMO

BACKGROUND: One of the most important aspects of designing a clinical trial is selecting appropriate outcomes. Patient-reported outcomes (PROs) can provide a personal assessment of the burden and impact of a malignant disease and its treatment. PROs comprise a wide range of outcomes including basic clinical symptom scores and complex metrics such as health-related quality of life (HRQoL). There is limited data on how postoperative complications following cancer surgery affect symptoms and HRQoL. For this reason the primary aim of the PATRONUS study is to investigate how perioperative complications affect cancer-related symptoms and HRQoL in patients undergoing abdominal cancer surgery. The PATRONUS study is designed and will be initiated and conducted by medical students under the direct supervision of clinician scientists based on the concept of inquiry-based learning. METHODS: PATRONUS is a non-interventional prospective multicentre cohort study. Patients undergoing elective oncological abdominal surgery will be recruited at regional centres of the clinical network of the German Surgical Society (CHIR-Net) and associated hospitals. A core set of 12 cancer associated symptoms will be assessed via the PRO version of the Common Terminology Criteria for Adverse Events. The cancer-specific HRQoL will be measured via the computerised adaptive testing version of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. PROs will be measured eight times over a period of six months. The short-term clinical outcome measure is the rate of postoperative complications (grade II to V) within 30 days according to the Clavien-Dindo classification. The long-term clinical outcome is overall survival within six months postoperative. DISCUSSION: PATRONUS will provide essential insights into the patients' assessment of their well-being and quality of life in direct relation to clinical outcome parameters following abdominal cancer surgery. Furthermore, PATRONUS will investigate the feasibility of multicentre student-led clinical research. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00013035 (registered on October 26, 2017). Universal Trial Number (UTN): U1111-1202-8863.


Assuntos
Abdome/cirurgia , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Estudos de Coortes , Procedimentos Cirúrgicos Eletivos/métodos , Humanos , Auditoria Médica , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Estudantes de Medicina
13.
Eur Respir J ; 50(1)2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28705941

RESUMO

The severity and lethality of influenza A virus (IAV) infections is frequently aggravated by secondary bacterial pneumonia. However, the mechanisms in human lung tissue that provoke this increase in fatality are unknown and therapeutic immune modulatory options are lacking.We established a human lung ex vivo co-infection model to investigate innate immune related mechanisms contributing to the susceptibility of secondary pneumococcal pneumonia.We revealed that type I and III interferon (IFN) inhibits Streptococcus pneumoniae-induced interleukin (IL)-1ß release. The lack of IL-1ß resulted in the repression of bacterially induced granulocyte-macrophage colony-stimulating factor (GM-CSF) liberation. Specific inhibition of IFN receptor I and III-associated tyrosine kinase 2 (Tyk2) completely restored the S. pneumoniae-induced IL-1ß-GM-CSF axis, leading to a reduction of bacterial growth. A preceding IAV infection of the human alveolus leads to a type I and III IFN-dependent blockade of the early cytokines IL-1ß and GM-CSF, which are key for orchestrating an adequate innate immune response against bacteria. Their virally induced suppression may result in impaired bacterial clearance and alveolar repair.Pharmacological inhibition of Tyk2 might be a new treatment option to sustain beneficial endogenous GM-CSF levels in IAV-associated secondary bacterial pneumonia.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Influenza Humana/tratamento farmacológico , Interferons/farmacologia , Pneumonia Bacteriana/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , TYK2 Quinase/antagonistas & inibidores , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos , Vírus da Influenza A , Influenza Humana/imunologia , Interleucina-1beta/metabolismo , Pulmão/efeitos dos fármacos , Pneumonia Bacteriana/imunologia , Infecções Estafilocócicas/imunologia , TYK2 Quinase/metabolismo
14.
Histochem Cell Biol ; 147(6): 707-719, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28247028

RESUMO

Loss of alveolar barrier function with subsequent respiratory failure is a hallmark of severe pneumonia. Although junctions between endo- and epithelial cells regulate paracellular fluid flux, little is known about their composition and regulation in the human alveolar compartment. High autofluorescence of human lung tissue in particular complicates the determination of subcellular protein localization. By comparing conventional channel mode confocal imaging with spectral imaging and linear unmixing, we demonstrate that background fluorescent spectra and fluorophore signals could be rigorously separated resulting in complete recovery of the specific signal at a high signal-to-noise ratio. Using this technique and Western blotting, we show the expression patterns of tight junction proteins occludin, ZO-1 as well as claudin-3, -4, -5 and -18 and adherence junction protein VE-cadherin in naive or Streptococcus pneumoniae-infected human lung tissue. In uninfected tissues, occludin and ZO-1 formed band-like structures in alveolar epithelial cells type I (AEC I), alveolar epithelial cells type II (AEC II) and lung capillaries, whereas claudin-3, -4 and -18 were visualised in AEC II. Claudin-5 was detected in the endothelium only. Claudin-3, -5, -18 displayed continuous band-like structures, while claudin-4 showed a dot-like expression. Pneumococcal infection reduced alveolar occludin, ZO-1, claudin-5 and VE-cadherin but did not change the presence of claudin-3, -4 and -18. Spectral confocal microscopy allows for the subcellular structural analysis of proteins in highly autofluorescent human lung tissue. The thereby observed deterioration of lung alveolar junctional organisation gives a structural explanation for alveolar barrier disruption in severe pneumococcal pneumonia.


Assuntos
Caderinas/metabolismo , Síndrome da Persistência do Padrão de Circulação Fetal/metabolismo , Infecções Pneumocócicas/metabolismo , Alvéolos Pulmonares/anormalidades , Humanos , Síndrome da Persistência do Padrão de Circulação Fetal/microbiologia , Infecções Pneumocócicas/microbiologia , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/microbiologia , Streptococcus pneumoniae
15.
Ann Surg ; 264(5): 745-753, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27741007

RESUMO

OBJECTIVE: This randomized controlled multicenter pilot trial was conducted to find robust estimates for the rates of recurrence of 2 surgical strategies for secondary hyperparathyroidism (SHPT) within 36 months of follow-up. BACKGROUND: SHPT is a frequent consequence of chronic renal failure. Total parathyroidectomy with autotransplantation (TPTX+AT) and subtotal parathyroidectomy (SPTX) are the standard surgical procedures. Total parathyroidectomy alone (TPTX) might be a good alternative, as morbidity and recurrence rates are low according to small-scale retrospective studies. METHODS: The trial was performed as a nonconfirmatory randomized controlled pilot trial with 100 patients on long-term dialysis with otherwise uncontrollable SHPT to generate data on the rate of recurrent disease within a 3-year follow-up period after TPTX or TPTX+AT. Parathyroid hormone (PTH) and calcium levels, recurrent or persistent hyperparathyroidism, parathyroid reoperations, morbidity, and mortality were evaluated during a 3-year follow-up. RESULTS: A total of 52 patients underwent TPTX and 48 TPTX+AT. Patient characteristics, preoperative baseline data, duration of surgery (02:29 vs 02:47 hrs, P = 0.17) and mean hospital stay (10 ± 7.1 vs 8 ± 3.7 days, P = 0.11) did not differ significantly. Persistent SHPT developed in 1 TPTX and 2 TPTX+AT patients. None of the TPTX patients required delayed parathyroid AT to treat permanent hypoparathyroidism. Serum-calcium values were similar (2.1 ± 0.3 vs 2.1 ± 0.2, P = 0.95) whereas PTH rose by time in the TPTX+AT group and was significantly higher at the end of follow-up when compared with the TPTX group (31.7 ± 43.6 vs 98.2 ± 156.8, P = 0.02). Recurrent SHPT developed in 4 TPTX+AT and none of the TPTX patients. CONCLUSIONS: TPTX+AT and TPTX seem to be safe and equally effective for the treatment of otherwise uncontrollable SHPT. TPTX seems to suppress PTH more effectively and showed no recurrences after 3 years. The hypothesis that TPTX is superior to TPTX+AT referring to the rate of recurrent SHPT has to be tested in a large-scale confirmatory trial. Nevertheless, TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of SHPT.


Assuntos
Hiperparatireoidismo Secundário/cirurgia , Glândulas Paratireoides/transplante , Paratireoidectomia , Timectomia , Adulto , Idoso , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Falência Renal Crônica/complicações , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Recidiva , Transplante Autólogo , Resultado do Tratamento
18.
Lancet ; 384(9938): 142-52, 2014 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-24718270

RESUMO

BACKGROUND: Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery, and triclosan-coated sutures were developed to reduce their occurrence. The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure, compared with non-coated PDS II sutures, in the prevention of surgical site infections. METHODS: This multicentre, randomised controlled group-sequential superiority trial was done in 24 German hospitals. Adult patients (aged ≥18 years) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion. Exclusion criteria were impaired mental state, language problems, and participation in another intervention trial that interfered with the intervention or outcome of this trial. A central web-based randomisation tool was used to randomly assign eligible participants by permuted block randomisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures (PDS Plus) or uncoated sutures (PDS II) for abdominal fascia closure. The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation. Patients, surgeons, and the outcome assessors were masked to group assignment. Interim and final analyses were by modified intention to treat. This trial is registered with the German Clinical Trials Register, number DRKS00000390. FINDINGS: Between April 7, 2010, and Oct 19, 2012, 1224 patients were randomly assigned to intervention groups (607 to PDS Plus, and 617 to PDS II), of whom 1185 (587 PDS Plus and 598 PDS II) were analysed by intention to treat. The study groups were well balanced in terms of patient and procedure characteristics. The occurrence of surgical site infections did not differ between the PDS Plus group (87 [14·8%] of 587) and the PDS II group (96 [16·1%] of 598; OR 0·91, 95% CI 0·66-1·25; p=0·64). Serious adverse events also did not differ between the groups-146 of 583 (25·0%) patients treated with PDS Plus had at least one serious adverse event, compared with 138 of 602 (22·9%) patients treated with PDS II; p=0·39). INTERPRETATION: Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy. Innovative, multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections. FUNDING: Johnson & Johnson Medical Limited.


Assuntos
Técnicas de Fechamento de Ferimentos Abdominais/efeitos adversos , Anti-Infecciosos Locais/administração & dosagem , Infecção da Ferida Cirúrgica/prevenção & controle , Suturas , Triclosan/administração & dosagem , Parede Abdominal , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
19.
BJS Open ; 8(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38242574

RESUMO

BACKGROUND: Adherence to enhanced recovery after surgery (ERAS) protocols is crucial for successful liver surgery. The aim of this study was to assess the impact of minimally invasive liver surgery complexity on adherence after implementing an ERAS protocol. METHODS: Between July 2018 and August 2021, a prospective observational study involving minimally invasive liver surgery patients was conducted. Perioperative treatment followed ERAS guidelines and was recorded in the ERAS interactive audit system. Kruskal-Wallis and ANOVA tests were used for analysis, and pairwise comparisons utilized Wilcoxon rank sum and Welch's t-tests, adjusted using Bonferroni correction. RESULTS: A total of 243 patients were enrolled and categorized into four groups based on the Iwate criteria: low (n = 17), intermediate (n = 81), advanced (n = 74) and expert difficulty (n = 71). Complexity correlated with increased overall and major morbidity rate, as well as longer length of stay (all P < 0.001; standardized mean difference = 0.036, 0.451, 0.543 respectively). Adherence to ERAS measures decreased with higher complexity (P < 0.001). Overall adherence was 65.4%. Medical staff-centred adherence was 79.9%, while patient-centred adherence was 38.9% (P < 0.001). Complexity significantly affected patient-centred adherence (P < 0.001; standardized mean difference (SMD) = 0.420), but not medical staff-centred adherence (P = 0.098; SMD = 0.315). Postoperative phase adherence showed major differences among complexity groups (P < 0.001, SMD = 0.376), with mobilization measures adhered to less in higher complexity cases. CONCLUSION: The complexity of minimally invasive liver surgery procedures impacts ERAS protocol adherence for each patient. This can be addressed using complexity-adjusted cut-offs and 'gradual adherence' based on the relative proportion of cut-off values achieved.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Fígado , Humanos , Fígado/cirurgia , Estudos Prospectivos
20.
Eur J Cardiothorac Surg ; 65(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38804185

RESUMO

OBJECTIVES: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading, Recommendation, Assessment, Development and Evaluation). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made. SHAREABLE ABSTRACT: This update of an ERS Task Force statement from 2015 provides a concise comprehensive update of the literature base. 24 evidence-based recommendations were made for management of pneumothorax, balancing clinical priorities and patient views.https://bit.ly/3TKGp9e.


Assuntos
Pneumotórax , Humanos , Pneumotórax/terapia , Adulto
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