Significant reduction of postoperative pain and opioid analgesics requirement with an Enhanced Recovery After Thoracic Surgery protocol

ObjectiveTo evaluate differences in postoperative pain control and opioids requirement in thoracic surgical patients following implementation of an Enhanced Recovery after Thoracic Surgery protocol with a comprehensive postoperative pain management strategy.Material and MethodsA retrospective analysis of a prospectively maintained database of patients undergoing pulmonary resections by robotic thoracoscopy or thoracotomy from January 1, 2017, to January 31, 2019, was conducted. Multimodal pain management strategy (opioid-sparing analgesics, infiltration of liposomal bupivacaine to intercostal spaces and surgical sites, and elimination of thoracic epidural analgesia use in thoracotomy patients) was implemented as part of Enhanced Recovery after Thoracic Surgery on February 1, 2018. Outcome metrics including patient-reported pain levels, in-hospital and postdischarge opioids use, postoperative complications, and length of stay were compared before and after protocol implementation.ResultsIn total, 310 robotic thoracoscopy and 62 thoracotomy patients met the inclusion criteria. This pain management strategy was associated with significant reduction of postoperative pain in both groups with an overall reduction of postoperative opioids requirement. Median in-hospital opioids use (morphine milligram equivalent per day) was reduced from 30 to 18.36 (P = .009) for the robotic thoracoscopy group and slightly increased from 15.48 to 21.0 (P = .27) in the thoracotomy group. More importantly, median postdischarge opioids prescribed (total morphine milligram equivalent) was significantly reduced from 480.0 to 150.0 (P < .001) and 887.5 to 150.0 (P < .001) for the thoracoscopy and thoracotomy groups, respectively. Similar short-term perioperative outcomes were observed in both groups before and following protocol implementation.ConclusionsImplementation of Enhanced Recovery after Thoracic Surgery allows safe elimination of epidural use, better pain control, and less postoperative opioids use, especially a drastic reduction of postdischarge opioid need, without adversely affecting outcomes.     

GLI inhibitors overcome Erlotinib resistance in human pancreatic cancer cells by modulating E-cadherin

Inhibition of hedgehog (Hh) signalling pathway, including its end effector GLI1, can reverse epithelial-to-mesenchymal transition (EMT) which plays an important role in drug resistance of pancreatic cancer cells to Erlotinib (ETB). This study investigated the effect of GLI inhibitors Forskolin (FSK), GANT-61 (GNT), and Arsenic trioxide (ATX) on suppressing the resistance of pancreatic cancer cells to ETB. The effect of GLI inhibitors was evaluated by measuring mRNA expression levels of EMT factors using quantitative RT-PCR. Immunocytochemistry and flow cytometry were used to assess E-cadherin (E-Cad) and GLI1 protein levels. MTT and apoptosis assays were used to evaluate the synergistic effects for the combination treatment of each GLI inhibitor with ETB. Pancreatic cancer cells PANC-1 treated by GNT showed the highest significant reduction in mRNA levels of GLI1 and other EMT pathway genes. Moreover, GNT was able to upregulate E-Cad and downregulate GLI1 proteins, more than FSK, while ATX had no effect. Apoptosis levels of PANC-1 cells following treatment with LD30 concentrations of FSK, GNT, or ATX, showed 57%, 62% and 67%, respectively, in comparison to ETB (～48%). Importantly, combination treatments of ETB with either FSK, GNT, or ATX demonstrated a significant increase in apoptotic cells reaching 61% (ETB?+?FSK), 80% (ETB?+?GNT) or 88% (ETB?+?ATX). FSK did not have much effect on the drug resistance of PANC-1 cells to ETB. However, GNT, but more effectively ATX, were able to reduce the drug resistance of this cell line to ETB.     

Berberine ameliorates experimental varicocele‐induced damages at testis and sperm levels; evidences for oxidative stress and inflammation

The present study was performed to show the ameliorative effect of berberine (BBR), as an antioxidant and anti‐inflammatory agent, against experimental varicocele (VCL)‐induced molecular and histological damages. For this purpose, 50 mature Wistar rats were divided into control, control‐sham, VCL‐sole, 50 mg/kg and 100 mg/kg BBR‐treated VCL‐induced groups. The tissue levels of interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α), nitric oxide (NO), total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD) and gluthatione peroxidase (GSH‐px) as well as the mRNA levels of testicular CuZn SOD, MnSOD, EC‐SOD and GSH‐px were evaluated. The serum concentration of testosterone and germ cells mRNA damage were analysed. Finally, the sperm viability, motility, DNA integrity and chromatin condensation were analysed. Observations revealed that, the BBR significantly downregulated VCL‐increased IL‐6, TNF‐α and NO levels, upregulated the CuZn SOD, MnSOD, EC‐SOD and GSH‐px mRNA level, decreased testicular MDA content, enhanced serum testosterone level and ameliorated testicular TAC, SOD and GSH‐px levels. The animals in BBR‐treated groups exhibited diminished mRNA damage versus non‐treated VCL‐induced group. The BBR has significantly (p < 0.05) improved sperm parameters. In conclusion, the BBR by promoting testicular antioxidant potential and by downregulating inflammatory reactions fairly promotes spermatogenesis and upregulates the sperm quality.     

Current status of simulation-based training in pediatric surgery: A systematic review

BackgroundSimulation based training enables pediatric surgical trainees to attain proficiency in surgical skills. This study aims to identify the currently available simulators for pediatric surgery, assess their validation and strength of evidence supporting each model.MethodsBoth Medline and EMBASE were searched for English language articles either describing or validating simulation models for pediatric surgery. A level of evidence (LoE) followed by a level of recommendation (LoR) was assigned to each validation study and simulator, based on a modified Oxford Centre for Evidence-Based Medicine classification for educational studies.ResultsForty-nine articles were identified describing 44 training models and courses. Of these articles, 44 were validation studies. Face validity was evaluated by 20 studies, 28 for content, 24 demonstrated construct validity and 1 showed predictive validity. Of the validated models, 3 were given an LoR of 2, 21 an LoR of 3 and 12 an LoR of 4. None reached the highest LoR.ConclusionsThere are a growing number of simulators specific to pediatric surgery. However, these simulators have limited LoE and LoR in current studies. The lack of NoTSS training is also apparent. We advocate more randomized trials to validate these models, and attempts to determine predictive validity.Type of studyOriginal / systematic review.Level of evidence1.     

The use of CMVIg rescue therapy in cardiothoracic transplantation: A single‐center experience over 6 years (2011‐2017)

Cytomegalovirus (CMV) is the most important infectious agent in solid organ transplant recipients and has a major impact on morbidity and mortality. Most cases are well managed with antiviral agents, but CMV hyperimmune globulin (CMVIg) can be used alongside antiviral therapy for prophylaxis in high‐risk thoracic organ recipients and to treat life‐threatening CMV infection or disease. CMVIg may also improve antiviral host defences when genetic resistance to antivirals or unwanted side effects occur. In this single‐center, retrospective study, we reviewed the CMVIg use to supplement antiviral therapy as a “rescue therapy” in cardiothoracic transplant recipients. These comprised 12 single lung, 11 double lung, and 12 heart transplant recipients. Patients received a median of 2 doses of CMVIg, most often in combination with ganciclovir or valganciclovir, and reduced immunosuppression. One week after rescue therapy was initiated, CMV DNA levels were significantly reduced, and after four weeks, CMV DNA was undetectable in 73% patients. Only one patient died as a result of CMV‐related disease. No significant adverse effects were observed. We conclude that CMVIg rescue therapy is safe, well tolerated, and effective at controlling viral replication in cardiothoracic transplant recipients.     

Contribution of Fc fragment of monoclonal antibodies to tetanus toxin neutralization

Neurotoxicity Research - Monoclonal antibodies (MAbs) against neurotoxin of Clostridium tetani are considered as a novel source of immunoglobulins for passive immunotherapy of tetanus. Toxin...