Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study.

(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation (ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse < 12 months from upfront therapy (15%), ≥2 lines of salvage therapy (73%), extranodal disease (65%). Nineteen patients (73%) had ≥3 of these factors. In addition, 16 patients (61%) also displayed PET-positive (Deauville ≥ 4) disease before ASCT. Treatment-related adverse events (TRAEs), never graded > 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6−30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients' subsets more likely to benefit from this approach.

Ultra-Fast-Track Extubation in Adult Congenital Heart Surgery.

Background In pediatric cardiac surgery, perioperative management has evolved from slow weaning of mechanical ventilation in the intensive care unit to "ultra-fast-track" anesthesia with early extubation (EE) in theater to promote a faster recovery. The strategy of EE has not been assessed in adults with congenital heart disease, a growing population of patients who often require surgery. Methods And Results Data were collected retrospectively on all patients >16 years of age who underwent adult congenital heart surgery in our tertiary center between December 2012 and January 2020. Coarsened exact matching was performed for relevant baseline variables. Overall, 711 procedures were performed: 133 (18.7%) patients underwent EE and 578 (81.3%) patients received conventional extubation. After matching, patients who received EE required less inotropic or vasopressor support in the early postoperative period (median Vasoactive-inotropic score 0.5 [0.0-2.0] versus 2.0 [0.0-3.5]; P<0.0001) and had a lower total net fluid balance than patients after conventional extubation (1168±723 versus 847±733 mL; P=0.0002). The overall reintubation rate was low at 0.3%. EE was associated with a significantly shorter postoperative length of stay in higher dependency care units before a "step-down" to ward-based care (48 [45-50] versus 50 [47-69] hours; P=0.004). Lower combined intensive care unit and high dependency unit costs were incurred by patients who received EE compared with patients who received conventional extubation (£3949 [3430-4222] versus £4166 [3893-5603]; P<0.0001). Conclusions In adult patients undergoing surgery for congenital heart disease, EE is associated with a reduced need for postoperative hemodynamic support, a shorter intensive care unit stay, and lower health-care-related costs.

Overview of Current Targeted Anti-Cancer Drugs for Therapy in Onco-Hematology.

The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells' inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy.

Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas.

The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis and the discovery of the critical role of tumor microenvironments have enabled the design of new drugs against cell targets and pathways. The Food and Drug Administration (FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) for targeted therapy in hematology. This review focuses on the efficacy results of the currently available targeted agents and recaps the main ongoing trials in the setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the different classes of novel agents approved for mature B-cell lymphomas, to describe in synoptic tables the results they achieved and, finally, to draw future scenarios as we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation (CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for improving survival outcome in lymphoid neoplasms, as well as the trade-offs between efficacy and toxicity. The hope for clinical advantages should carefully be coupled with mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes severe, toxicities.

A multicenter audit of the use of bronchoscopy during open and thoracoscopic repair of esophageal atresia with tracheoesophageal fistula.

BACKGROUND: Esophageal atresia (EA) with tracheoesophageal fistula is usually repaired in the neonatal period. Preferential ventilation through the fistula can lead to gastric distension. Bronchoscopy has a role in defining the site and size of the fistula, and may be carried out by the surgeon or the anesthetist. The use of bronchoscopy varies across different institutions. METHODS: This is a multicenter case note review of infants with EA with tracheoesophageal fistula who underwent surgery between January 2010 and December 2015. This retrospective audit aims primarily to document the use of bronchoscopy during open and thoracoscopic repair at a selection of United Kingdom centers. Respiratory complications, that is relating to airway management, the respiratory system, and difficulty with ventilation, at induction and during surgery, are recorded. The range of techniques for anesthesia and analgesia in these centers is noted. RESULTS: Bronchoscopy was carried out in 52% of cases. The incidence of respiratory complications was 7% at induction and 21% during surgery. Thoracoscopic repair usually took longer. One center used high-frequency oscillatory ventilation, on an elective basis during thoracoscopic repair, to facilitate surgical access and address concerns about hypoxemia and hypercarbia. CONCLUSION: The use of bronchoscopy varies considerably between institutions. Infants undergoing tracheoesophageal fistula repair are at risk of perioperative respiratory morbidity. The advent of thoracoscopic repair has introduced further variation.

Anaerobic metabolism during cardiopulmonary bypass: predictive value of carbon dioxide derived parameters.

BACKGROUND: Hyperlactatemia during cardiopulmonary bypass (CPB) is a common event and is associated to a high morbidity and mortality after cardiac operations. The present study is aimed to identify the possible predictors of hyperlactatemia during CPB among a series of oxygen and carbon dioxide derived parameters measured during CPB. METHODS: This is a prospective observational study on 54 patients undergoing cardiac surgery with CPB. Hyperlactatemia was defined as an arterial lactate concentration higher than 3 mMol/L. Serial blood lactate assays have been performed during CPB, and their association to a number of oxygen and carbon dioxide derived parameters was explored. RESULTS: Arterial blood lactate concentration was positively correlated to the CPB duration, the carbon dioxide elimination, and the respiratory quotient, and negatively correlated to the presence of the aortic cross-clamping, the body surface area, the ratio between the oxygen delivery and the carbon dioxide production, and the arterial oxygen saturation. Predictors of hyperlactatemia during CPB are a carbon dioxide production higher than 60 mL.min(-1).m(-2), a respiratory quotient higher than 0.9, and a ratio between oxygen delivery and carbon dioxide production lower than 5. CONCLUSIONS: Carbon dioxide derived parameters are representative of hyperlactatemia during CPB, as a result of the carbon dioxide produced under anaerobic conditions through the buffering of protons by the bicarbonate system. The carbon dioxide elimination rate measured at the exhaled site of the oxygenator may be used for an indirect assessment of the metabolic state of the patient.