Adjuvant Nivolumab for Localized Renal Cell Carcinoma at High Risk of Recurrence After Nephrectomy: Part B of the Randomized, Placebo-Controlled, Phase III CheckMate 914 Trial.

PURPOSE: CheckMate 914 is a two-part, randomized phase III trial evaluating adjuvant nivolumab plus ipilimumab (part A) or adjuvant nivolumab monotherapy (part B) versus placebo in mutually exclusive populations of patients with localized renal cell carcinoma (RCC) at high risk of postnephrectomy recurrence. Part A showed no disease-free survival (DFS) benefit for adjuvant nivolumab plus ipilimumab versus placebo. We report results from part B. METHODS: Patients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point. RESULTS: Overall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively. CONCLUSION: Part B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.

Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial.

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2-20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1-69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7-13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05-0.87). A total of 56.2% (95% CI 41.1-70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).

Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability. METHODS: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary study end point was rate of pathologic response (defined as < ypT2N0). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety and tolerability. RESULTS: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response (95% CI, 49 to 76). A complete pathologic response (ypT0N0) was noted in 11 patients (19%). Fifty-one patients (89%) tolerated at least three complete cycles of split-dose GC, 27 patients (47%) tolerated four complete cycles, and all patients proceeded to surgery. With a median follow up of 3.1 years, 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. Pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95% v 76%, P < .001; 2-year OS 100% and 100% v 80%, P < .001). CONCLUSION: NAC with split-dose GC for high-risk UTUC is a well-tolerated, effective therapy demonstrating evidence of pathologic response that is associated with favorable survival outcomes. Given that these survival outcomes are superior to historical series, these data support the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC.

Routine Application of Lung Ultrasonography in Respiratory Care: Knowledge, Perceptions, and Barriers to Instigate.

Background: Lung Ultrasound (LUS) had proved to be beneficial in detecting respiratory disorders at the bedside. Understanding the important role of Respiratory Therapists (RTs) in the critical care, we aimed to assess their knowledge, perceived relevance of LUS to clinical practice, current skill gaps, and barriers to practice. Methods: A cross-sectional, nationwide survey conducted among the RTs working in the Kingdom of Saudi Arabia. The validated questionnaire included 4 sections; the demographics, knowledge and perceptions, applicability and self-reported proficiency, and barriers to the use of LUS by RTs. Results: A total of 256 RTs across different regions of Saudi Arabia participated in this survey. 71.9% of them were males, and 46.1% of the participants were having <5 years of working experience. Only (18.1%) of the participants used LUS in their clinical practice, and (43%) of them had never received any training. 66% of the participants perceived LUS as an effective tool in the RT practice and immensely valuable in their daily practice (70%). A large proportion of RTs perceived LUS to be ineffective in calculating the lung score (50.4%), assessing the diaphragm (40.2%), and detecting pulmonary edema (38.3%). Calculating lung score has a lower mean score of 2.55 on both skills, and identifying its applicability to clinical practice with a mean score of 2.71 than other indications. Lack of training and curriculum (154/256; 60.2%) remains the top barrier that prevented RTs from using LUS in their clinical practice. Conclusion: While many RTs in Saudi Arabia perceived LUS as an effective tool in the RT practice, considerable competence gap exist, indicating the need for LUS training. There is a need for incorporating LUS into the curriculum of RT schools and promoting competency-based training for the current RT workforce to help improve patient care.

Anesthetic Challenges and Perioperative Factors Affecting Delayed Graft Function in Robotic-Assisted Kidney Transplant: A Review of a Single-Center Experience of 100 Cases.

Background and objective The advent of robot-assisted kidney transplant (RAKT) has ushered in a new set of challenges. In this single-center retrospective observational study, we aimed to highlight the anesthetic challenges and analyze perioperative parameters to identify the risk factors for delayed graft function (DGF) in RAKT. Methods A descriptive analysis of perioperative factors of the first 100 cases of RAKT at our center was performed. Data were retrieved from the hospital's electronic medical records (EMR) of donors and adult patients who underwent RAKT between July 2015 and December 2020. The data analyzed included demographics, preoperative optimization, intraoperative and postoperative management, and complications. DGF was defined as a requirement of dialysis within one week of transplant. The Fisher's exact test, independent sample t-test, and the Mann-Whitney test were used to analyze data. Results Among a total of 193 renal transplants performed during the study period, 100 patients underwent RAKT, which included 27 females and 73 males. Of these, 91 were live while the remaining involved deceased-donor transplants. Pneumoperitoneum and steep Trendelenburg position required various "anesthetic maneuvers" to maintain hemodynamics and respiratory parameters. Optimal fluid management, with frusemide and mannitol, ensured good urine output (UOP) (93%). Post-reperfusion, the release of pneumoperitoneum, maintenance of adequate perfusion pressures, immunosuppression, and regional hypothermia helped in ensuring adequate graft function (93%). The incidence of DGF in our series was 7% and the mortality rate was 3%. Recipient age (p=0.045), dyslipidemia (p=0.021), and diabetes mellitus (p=0.023) were identified as significant risk factors for DGF. Conclusion Advanced recipient age, diabetes, and dyslipidemia were factors significantly associated with DGF in RAKT in our series of 100 cases. However, the duration of the steep Trendelenburg position, docking of robot/pneumoperitoneum (console time), fluid management, warm and cold ischemia times, rewarming time, and type of graft did not influence DGF. Awareness of the systemic involvement in RAKT, proper preoperative optimization, and knowledge of potential problems are essential for the efficient anesthetic management of RAKT.

Immunoscore Is Prognostic in Low-Risk and High-Risk Stage III Colon Carcinomas Treated With Adjuvant Infusional Fluorouracil, Leucovorin, and Oxaliplatin in a Phase III Trial.

PURPOSE: The recommended duration of adjuvant fluoropyrimidine and oxaliplatin chemotherapy for patients with stage III colon cancer is based on tumor classification into clinically low-risk (T1-3 N1) and high-risk (T4 or N2) groups. We determined whether Immunoscore can enhance prognostication within these risk groups. MATERIALS AND METHODS: Patients with stage III colon carcinomas (N = 600) were randomly selected from the infusional fluorouracil, leucovorin, and oxaliplatin arm of adjuvant trial NCCTG N0147 (Alliance for Clinical Trials in Oncology). Tumors were evaluated for Immunoscore that quantifies CD3+ and CD8+ T-cell densities in the tumor center and invasive margin by digital image analysis. Disease-free survival (DFS) by Immunoscore was analyzed using a multivariable Cox regression model in each risk group with adjustment for covariates including KRAS, BRAFV600E, and mismatch repair status. RESULTS: Of 559 cancers with Immunoscore data, 299 (53.5%) were classified as clinically low-risk (T1-3 N1) and 260 (46.5%) as clinically high-risk (T4 and/or N2). Among patients with low-risk tumors, those with Immunoscore-Low versus Immunoscore-High tumors had significantly worse 5-year DFS rates (77.5% v 91.8%; hazard ratio, 1.70; 95% CI, 1.03 to 2.79; P = .037). Among patients with high-risk tumors, those with Immunoscore-Low versus Immunoscore-High tumors also had significantly worse DFS (55.3% v 70.3%; hazard ratio, 1.65; 95% CI, 1.11 to 2.47; P = .013). Tumors that were low-risk/Immunoscore-Low had similar outcomes as did tumors that were high-risk/Immunoscore-High (P = .174). Prognostication was significantly improved in multivariable models where Immunoscore was added to clinical risk parameters and limited biomarkers (likelihood ratio test P = .0003). CONCLUSION: Immunoscore can refine patient prognosis beyond clinical risk group classification, suggesting its potential utility for adjuvant decision making.

Extracorporeal cardiopulmonary resuscitation for an out-of-hospital cardiac arrest.

Extra corporeal membrane oxygenation (ECMO) for refractory out-of-hospital cardiac arrest (OHCA) has been shown to improve outcome in many Western countries. There are no reports of ECMO being used to support OHCA in India till date. We report a case of a young man who developed cardiac arrest (CA) while driving and was given bystander cardiac massage. He was brought to tertiary care center where an ECMO was utilized for refractory CA. The patient subsequently underwent emergency coronary artery stenting and was weaned off ECMO and ventilation. We discuss the case and highlight the role of bystander cardiopulmonary resuscitation.

Multilayer perceptron neural network model development for mechanical ventilator parameters prediction by real time system learning.

BACKGROUND AND OBJECTIVE: In pandemic situations like COVID 19, real time monitoring of patient condition and continuous delivery of inspired oxygen can be made possible only through artificial intelligence-based system modeling. Even now manual control of mechanical ventilator parameters is continuing despite the ever-increasing number of patients in critical epidemic conditions. Here a suggestive multi-layer perceptron neural network model is developed to predict the level of inspired oxygen delivered by the mechanical ventilator along with mode and positive end expiratory pressure (PEEP) changes for reducing the effort of health care professionals. METHODS: The artificial neural network model is developed by Python programming using real time data. Parameter identification for model inputs and outputs is done by in corporating consistent real time patient data including periodical arterial blood gas analysis, continuous pulse oximetry readings and mechanical ventilator settings using statistical pairwise analysis using R programming. RESULTS: Mean square error values and R values of the model are calculated and found to be an average of 0.093 and 0.81 respectively for various data sets. Accuracy loss will be in good fit with validation loss for a comparable number of epochs. CONCLUSIONS: Comparison of the model output is undertaken with physician's prediction using statistical analysis and shows an accuracy error of 4.11 percentages which is permissible for a good predictive system.

Risk stratification after recurrence of human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancer: Secondary analysis of NRG Oncology RTOG 0129 and 0522.

BACKGROUND: No risk-stratification strategies exist for patients with recurrent oropharyngeal cancer (OPC). METHODS: Retrospective analysis using data from prospective NRG Oncology clinical trials RTOG 0129 and 0522. Eligibility criteria included known p16 status and smoking history, and locoregional/distant recurrence. Overall survival (OS) was measured from date of recurrence. Recursive partitioning analysis was performed to produce mutually exclusive risk groups. RESULTS: Hundred and fifty-four patients were included with median follow-up after recurrence of 3.9 years (range 0.04-9.0). The most important factors influencing survival were p16 status and type of recurrence, followed by surgical salvage and smoking history (≤20 vs. >20 pack-years). Three significantly different risk groups were identified. Patients in the low-, intermediate-, and high-risk groups had 2-year OS after recurrence of 81.1% (95%CI 68.5-93.7), 50.2% (95%CI 36.0-64.5), and 20.8% (95%CI 10.5-31.1), respectively. CONCLUSION: Patient and tumor characteristics may be used to stratify patients into risk groups at the time of OPC recurrence.

Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study).

PURPOSE: Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear. METHODS: The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study (NCT03122522) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety. RESULTS: Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity. CONCLUSION: The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi.

Comparison of efficacy of two different doses of tranexamic acid in prevention of post operative blood loss in patients with congenital cyanotic heart disease undergoing cardiac surgery.

Background: The optimal dose of tranexamic acid in minimizing perioperative bleeding is uncertain. We compared efficacy of two different doses of tranexamic acid in reducing post-operative blood loss and its side effects in patients with congenital cyanotic heart disease undergoing cardiac surgery. Settings and Design: Prospective observational study at a pediatric cardiac center in South India. Methods: Consecutive cyanotic patients undergoing cardiac surgery were divided into groups I and II to receive either 10 mg/kg or 25 mg/kg of tranexamic acid administered as triple dose regime after induction, during cardiopulmonary bypass, and after protamine. Post-operative blood loss at 24 hours, blood component utilization, incidence of renal dysfunction and seizures were compared. Results: Totally, 124 patients were recruited, 62 in each group. The pre-operative variables and cardiopulmonary bypass time were comparable. Patients receiving 25 mg/kg had lower post-operative blood loss compared to patients in lower dose group (8.04 ± 8.89 vs 12.41 ± 19.23 ml/kg/24 hours, P = 0.03). There was no difference in the transfused volume of packed red cells (9.21 ± 7.13 ml/kg vs 12.41 ± 9.23 ml/kg, P = 0.712), fresh frozen plasma (13.91 ± 13.38 ml/kg vs 11.02 ± 8.04 ml/kg, P = 0.19), platelets (9.03 ± 6.76 ml/kg vs 10.90 ± 6.9 ml/kg, P = 0.14) or cryoprecipitate (0.66 ± 0.59 ml/kg vs 0.53 ± 0.54 ml/kg, P = 0.5) in group II and I, respectively. Two patients developed renal dysfunction secondary to low cardiac output in lower dose group. There were no seizures. Conclusions: Tranexamic acid administered at a dose of 25 mg/kg as triple dose regime is associated with lower post-operative blood loss compared to a lower dose of 10 mg/kg in cyanotic patients undergoing cardiac surgery without causing major adverse effects.

Critical care as a career for anaesthesiologists.

Anaesthesiologists by virtue of their understanding of physiology, pharmacology and resuscitation skills are best suited to manage critical care units. Armed with this varied knowledge, the anaesthesiologist is 'physician to the surgeon and a surgeon to the physician'. Specialised training helps them to provide extended postoperative and critical care. During the past few months in the battle with coronavirus disease (COVID)-19, anaesthesiologists have stood up to the challenge of caring for critically ill patients, compromising on their operating room responsibilities. The fact from a growing body of literature suggests that an anaesthesiologist as a critical care specialist provides efficient care and better outcomes. With an increasing awareness and need for critical care, government support is going to increase with an increase in avenues for training and research leading to better professional development and earning potential.

Malignant hyperthermia during pediatric kidney transplantation-A medical and ethical quandary.

Malignant hyperthermia (MH) is a rare life-threatening anesthetic complication with high mortality rates. MH during adult kidney transplant has been reported previously. However, the occurrence of MH after multiple previous uneventful anesthetic exposures in a pediatric kidney transplant recipient is rare. To our knowledge, this is the first reported case of MH in a child undergoing a live donor kidney transplant. The approaches for addressing perioperative challenges and ethical dilemmas to ensure successful outcomes are described. The recipient, a 5-year-old male child, weighing 20 kg, with a history of multiple previous uneventful anesthetic exposures, underwent live donor kidney transplant for end-stage renal disease (ESRD). Post-reperfusion he developed fulminant MH with rapidly progressing hyperthermia, hypercarbia, tachycardia, and muscle rigidity, which in addition to complicating the medical management raised several ethical issues as well. MH was successfully managed with dantrolene and other supportive measures. Judicious use of inotropes and fluids helped maintain stable hemodynamics and graft perfusion. Management of MH is complicated in a pediatric patient with ESRD undergoing live donor kidney transplant. Preference for non-depolarizing muscle relaxants instead of succinylcholine during endotracheal intubation can result in delayed onset of clinical manifestations. However, the metabolic complications may be more severe due to preexisting electrolyte and acid-base disturbances. Maintaining optimal graft perfusion while simultaneously combating MH can be very challenging in a child. Since the allograft is a precious commodity, critical decisions regarding the harvesting of the donor kidney need to be well thought out. Early diagnosis and prompt treatment with dantrolene are critical to preserving graft function and the recipient's life.

Contribution of Immunoscore and Molecular Features to Survival Prediction in Stage III Colon Cancer.

BACKGROUND: The American Joint Committee on Cancer staging and other prognostic tools fail to account for stage-independent variability in outcome. We developed a prognostic classifier adding Immunoscore to clinicopathological and molecular features in patients with stage III colon cancer. METHODS: Patient (n = 559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 were used to construct Cox models for predicting disease-free survival (DFS). Variables included age, sex, T stage, positive lymph nodes (+LNs), N stage, performance status, histologic grade, sidedness, KRAS/BRAF, mismatch repair, and Immunoscore (CD3+, CD8+ T-cell densities). After determining optimal functional form (continuous or categorical) and within Cox models, backward selection was performed to analyze all variables as candidate predictors. All statistical tests were two-sided. RESULTS: Poorer DFS was found for tumors that were T4 vs T3 (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.19 to 2.60; P = .004), right- vs left-sided (HR = 1.52, 95% CI = 1.14 to 2.04; P = .005), BRAF V600E (HR = 1.74, 95% CI = 1.26 to 2.40; P < .001), mutant KRAS (HR = 1.66, 95% CI = 1.08 to 2.55; P = .02), and low vs high Immunoscore (HR = 1.69, 95% CI = 1.22 to 2.33; P = .001) (all P < .02). Increasing numbers of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both Ps< .0001). After number of +LNs, T stage, and BRAF/KRAS, Immunoscore was the most informative predictor of DFS shown multivariately. Among T1-3 N1 tumors, Immunoscore was the only variable associated with DFS that achieved statistical significance. A nomogram was generated to determine the likelihood of being recurrence-free at 3 years. CONCLUSIONS: The Immunoscore can enhance the accuracy of survival prediction among patients with stage III colon cancer.

Genetic Variant Associated With Survival of Patients With Stage II-III Colon Cancer.

BACKGROUND & AIMS: Many genetic variants have been associated with colorectal cancer risk, although few have been associated with survival times of patients. Identification of genetic variants associated with survival times might improve our understanding of disease progression and aid in outcome prediction. We performed a genome-wide association study to identify variants associated with colon cancer survival time. METHODS: We performed a post hoc analysis of data from NCCTG N0147 (Alliance), a randomized phase 3 trial of patients with resected stage III colon cancer, and from NSABP C-08 (NRG), a phase 3 trial that compared therapy regimens for patients with resected stage II or III colon cancer. Genotype analyses were performed on DNA from blood samples from 4974 patients. We used Cox proportional hazards regression to evaluate the association of each single nucleotide polymorphism with times of overall survival and disease-free survival, adjusting for age at diagnosis, sex, treatment group, and principal components of genetic ancestry. We performed the analysis for studies N0147 and C-08 separately, and results were combined in a fixed-effects meta-analysis. RESULTS: A locus on chromosome 7p15.2 was significantly associated with overall survival time (P ≤ 5x10-08). The most significant variant at this locus, rs76766811 (P = 1.6x10-08), is common among African Americans (minor allele frequency, approximately 18%) but rare in European Americans (minor allele frequency <0.1%). Within strata of self-reported ancestry, this variant was associated with times of overall survival and disease-free survival in only African Americans (hazard ratio for overall survival, 2.82; 95% CI, 1.88-4.23; P = 5.0x10-07 and hazard ratio for disease-free survival, 2.27; 95% CI, 1.62-3.18; P = 1.8x10-06). CONCLUSIONS: In an analysis of data from 2 trials of patients with stage II or III colon cancer, we identified rs76766811 as a potential prognostic variant in African American patients. This finding should be confirmed in additional study populations. ClinicalTrials.gov Identifiers: NCT00096278 (NSABP C-08) and NCT00079274 (NCCTG N0147).

Comparison of Blood-Conserving and Allogenic Transfusion-Sparing Effects of Antifibrinolytics in Scoliosis Correction Surgery.

BACKGROUND: Intraoperative antifibrinolytic drug administration is a safe and effective method of reducing blood loss and allogenic transfusions in patients undergoing spine deformity correction. AIM: This study aimed to compare the effectiveness of two antifibrinolytic drugs tranexamic acid (TXA) and epsilon amino caproic acid (EACA) in reducing peri-operative blood loss and transfusion requirements against a placebo control in patients with idiopathic scoliosis undergoing correction surgery. SETTING AND DESIGN: This is a prospective, randomized, double-blinded, controlled comparative study. METHODOLOGY: Patients in TXA group received 50 mg.kg-1 bolus and 10 mg.kg-1.h-1 infusion as against 100 mg.kg-1 and 10 mg.kg-1.h-1 infusion in EACA group. The placebo group had saline bolus and infusion. Parameters observed included baseline demographic and deformity data, duration of surgery, total peri-operative blood loss, and allogenic packed red cell transfusion requirements. STATISTICAL ANALYSIS: Mean and standard deviation were used to represent the quantitative continuous data, and percentage was used to represent categorical data. The Student's t-test and ANOVA were used to compare means between groups. Bonferroni's multiple comparison test was used to find out the association between categorical variables. RESULTS: A total of 36 patients were enrolled with 12 patients in each group. Peri-operative blood loss was 50.1% lower in patients receiving TXA and 17.7% lower in patients receiving EACA compared with the placebo group. The volume of total packed red cell transfusion was 66.7% lower in patients receiving TXA and 45.6% lower in patients receiving EACA compared with placebo. CONCLUSION: TXA was more effective in reducing total peri-operative blood loss and allogenic transfusion requirement in idiopathic scoliosis correction surgery compared to EACA.

Common inflammatory markers after cardiac surgery in infants and their relation to blood stream sepsis.

BACKGROUND: Limited information exists on trends of common inflammatory markers after infant heart surgery and their role in identifying post-operative sepsis. METHODS: 275 consecutive infants undergoing cardiac surgery (231 with and 44 without Cardiopulmonary Bypass) were studied prospectively. Daily trends (0-4 day post-operative) of leucocyte counts, platelet counts and C-reactive protein were recorded. Association of these trends with early post-operative bloodstream sepsis, Cardiopulmonary Bypass and surgical outcomes were studied. OBSERVATIONS: Trends of these inflammatory markers were noted. While off-Cardiopulmonary Bypass Surgery, and sepsis were associated with a statisticaly insignificant rise in total leucocyte count peaking on first post-operative day, Cardiopulmonary Bypass exposure was associated with significant decline (p = 0.002), more pronounced with Cardiopulmonary Bypass-exposure exceeding 150 min. Percentage of neutrophils showed a rise (maximum on first post-operative day) but no significant association with sepsis or Cardiopulmonary Bypass.Platelet counts significantly declined after surgery, with nadir on 2nd POD (p < 0.001), the drop being more marked in patients operated on Cardiopulmonary Bypass (p < 0.005). Counts were significantly lower in patients exposed to >150 min Cardiopulmonary Bypass compared to those with shorter Cardiopulmonary Bypass. Septic patients had significantly lower platelet counts than uninfected patients, decline >2 SD from mean pre-operative level strongly associated with sepsis (p < 0.001).C-Reactive Protein levels rose markedly after surgery, peaking on 2nd POD; levels were significantly higher if operated on Cardiopulmonary Bypass. Cardiopulmonary Bypass >150 min was associated with lower mean C-Reactive Protein on first post-operative day, but significantly higher values on third and fourth post-operative days, as compared to Cardiopulmonary Bypass <150 min. Comparison of infected versus non-infected patients showed significantly higher mean C-Reactive Protein in the former group. CONCLUSION: While leucocyte count, platelet count and C-Reactive Protein emerged as useful markers of post-operative inflammatory response and reaction to Cardiopulmonary Bypass, they proved unsatisfactory predictors of early post-operative sepsis.

Analysis of parameters affecting blood oxygen saturation and modeling of fuzzy logic system for inspired oxygen prediction.

BACKGROUND AND OBJECTIVE: Fraction of Inspired Oxygen is one of the arbitrary set ventilator parameters which has critical influence on the concentration of blood oxygen. Normally mechanical ventilators providing respiratory assistance are tuned manually to supply required inspired oxygen to keep the oxygen saturation at the desired level. Maintaining oxygen saturation in the desired limit is so vital since excess supply of inspired oxygen leads to hypercapnia and respiratory acidosis which lead to increased risk in cell damage and death. On the other side a sudden drop in oxygen saturation will lead to severe cardiac arrest and seizure. Hence intelligent real time control of blood oxygen level saturation is highly significant for patients in intensive care units. METHODS: This paper gives statistical pair wise analysis for finding out deeply correlated physiological parameters from clinical data for fixing fuzzy variables. An advisory fuzzy controller using Mamdani model is developed with R programming to predict FiO2 which is to be delivered from the ventilator to maintain SaO2 with in required levels. RESULTS: Fuzzy variables for the fuzzy model is fixed using 75% of the clinical data collected. Remaining 25% of the data is used for checking the system. Compared the predictive output of the system with physicians' decisions and found to be accurate with less than five percentage error. CONCLUSIONS: Based on the comparison the system is proved to be effective and can be used as assist mode for physicians for effective decision making.