Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis / Controle intensivo da glicose em adultos em estado grave: um protocolo de revisão sistemática e metanálise de dados individuais de pacientes

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?' Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869

RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869

Management of intrathoracic phosphaturic mesenchymal tumor by nonintubated uniportal video-assisted thoracic surgery in a fragile patient.

BACKGROUND: Phosphaturic mesenchymal tumors are rare neoplasms, frequently presenting with osteomalacia. These neoplasms usually grow at a slow rate and are associated with unspecific symptoms. CASE: In this study, we present the case of a 70-year-old woman who had been suffering from musculoskeletal pain, hypophosphatemia, and spontaneous fractures. Positron emission tomography with Gallium showed increase uptake in a subpleural lesion. CONCLUSION: The patient underwent surgical excision of the subpleural lesion with a non-intubated uniportal video-assisted thoracoscopic surgery approach.

Heparin-Free Lung Transplantation on Venovenous Extracorporeal Membrane Oxygenation Bridge.

Extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation (LuTX) exposes the patients to a high risk of perioperative bleeding secondary to systemic anticoagulation and coagulation factors deficiency. With this case series, we propose innovative "no-heparin" management of ECMO-bridge support during LuTX, based upon 1) control heparin resistance with antithrombin III in the preoperative period; 2) relying upon a fully functional, brand new heparinized ECMO circuit; 3) completely avoiding perioperative heparin; 4) hampering fibrinolysis with tranexamic acid; and 5) limiting venoarterial (VA) ECMO escalation, and the following need for full anticoagulation. Following the application of this new approach, we carried out three challenging clinical cases of bilateral ECMO-bridged LuTX effectively, with limited intraoperative blood requirement and no major postoperative bleeding or thromboembolic events. Of note, two of them had an extremely high risk for hemorrhage due to complete right lung anatomic derangement in case number 2 and surgical adhesion following first LuTX in case number 3, while for the case number 1, no blood products were administered during surgery. Despite the limited patient population, such an approach relies on a strong rationale and may be beneficial for managing ECMO bridging to LuTX. Prospective studies are necessary to confirm the validity of our strategy.

Percutaneous lung microwave ablation versus lung resection in high-risk patients. A monocentric experience.

BACKGROUND AND AIM OF WORK: Lung microwave ablation (MWA) is considered an alternative treatment in high-risk patients, not suitable for surgery. The aim of our study is to compare MWA and pulmonary lobectomy in high-risk, lung cancer patients. METHODS: This was a single-center, propensity score--weighted cohort study. All adult patients who underwent CT guided MWA for stage I NSCLC between June 2009-October 2014 were included in the study and were compared with a cohort of patients submitted to lung lobectomy in the same period of time. Outcomes were overall survival (OS) and disease-free survival (DFS). RESULTS: 32 patients underwent MWA, and 35 high-risk patients submitted to lung lobectomy in the same period were selected. Median follow-up time was 51.1 months (95% CI: 43.8-62.3). Overall survival was 43.8 (95% CI: 26.1-55) and 55.8 months (95% CI: 49.9-76.8) in the MWA group and Lobectomy group, respectively. Negative prognostic factors were MWA procedure (HR:2.25, 95% CI: 1.20-4.21, p= 0.0109) and nodule diameter (HR: 1.04, 95% CI: 1.01-1.07; p= 0.007) for OS, while MWA procedure (HR: 5.2; 95% CI: 2.1-12.8: p < 0.001), ECOG 3 (HR: 5.0; 95% CI: 1.6-15.6; p = 0.006) and nodule diameter (HR: 1.1; 95% CI: 1.0-1.1; p = 0.003) for DFS. CONCLUSIONS: Our study demonstrated a high percentage of local relapse in the MWA group but a comparable overall survival. Although lung lobectomy remains the gold standard treatment for stage I NSCLC, we can consider the MWA procedure as valid alternative local treatment in high-risk patients for stage I NSCLC.

Intraoperative extracorporeal membrane oxygenation for lung transplantation in cystic fibrosis patients: Predictors and impact on outcome.

BACKGROUND: Predictors and outcomes of intraoperative extracorporeal membrane oxygenation (ECMO) during lung transplantation (LUTX) for cystic fibrosis (CF) are unknown. METHODS: We retrospectively collected the clinical data at enlistment of the CF patients who underwent double LUTX from January 2013 to December 2018 at an Italian tertiary referral center. We compared blood transfusions, incidence of primary graft dysfunction (PGD), duration of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS and survival of ECMO and non-ECMO patients. Chi-square, Kruskal-Wallis, and log-rank tests were used. RESULTS: Twenty-eight (40%) of the 70 included patients needed intraoperative central veno-arterial ECMO with postoperative veno-venous prolongation in 6 subjects. Lower right ventricle ejection fraction (p = 0.013, OR 0.92(0.86-0.98)), higher oxygen requirement (p = 0.026, OR 1.39(1.01-1.90)), lower body surface area (p = 0.044, OR 0.05(0.00-1.03)), and CF-related diabetes (p = 0.044, OR 2.81(1.03-7.66)) were associated with intraoperative ECMO. Compared to non-ECMO patients, ECMO patients needed almost fivefold intraoperative transfusion (2227 mL vs. 570 mL, p<0.001) and had PGD grade > 0 at 72 h more frequently (16/57% vs. 12/28%, p = 0.017, OR 3.33(1.22-9.09)). Mechanical ventilation, ICU LOS and hospital LOS were significantly longer in ECMO patients. Survival at follow-up (651(326-1277) days) of ECMO and non-ECMO patients was 78% vs. 83%, respectively (OR 0.73 (0.21-2.46), p = 0.616, log-rank test p = 0.498). CONCLUSION: Pre-operative risk assessment and clinical planning should be done according to the predictors above. While undeniably useful as a life-saving procedure, ECMO during LUTX for CF is associated with worsened short-term outcomes. ECMO should be implemented weighing its risk and benefits.

Oxygenation during general anesthesia and thoracic surgery in a patient with Titusville low-oxygen affinity hemoglobin.

The purpose of this case study is to describe the physiological characteristics of a patient with the low-oxygen affinity Titusville hemoglobin variant. A 46-yr-old man with exertional dyspnea was diagnosed with a mediastinal lymphadenopathy of unknown origin and, to obtain definitive diagnosis by biopsy, underwent endobronchial ultrasound-guided transbronchial needle aspirate under sedation and video-assisted thoracoscopy under general anesthesia. High inspired fraction of oxygen ( FIO2 ) was used to guarantee adequate oxygenation even during the one-lung ventilation needed for thoracoscopy. Following radial and pulmonary arterial catheterization, continuous mixed-venous oxygen saturation ( SVO2 ), cardiac output, oxygen delivery (DO2), oxygen consumption (V̇o2), and oxygen extraction ratio (ERO2) were measured. Serial blood gas analyses were obtained at different FIO2 . Anesthesia and surgery were carried out safely. Data obtained during the clinical case were utilized to 1) construct an in vivo Titusville hemoglobin dissociation curve and 2) describe oxygen delivery and consumption of a human with Titusville mutation. Titusville hemoglobin showed relatively high P50 (i.e., 30 vs. normal of 27) and very low cooperativity (Hill coefficient of 1.45 vs. normal 2.27), which was compensated in our patient by increases in cardiac output, rather than by augmenting oxygen extraction.