Effect of abnormal liver function test on maternal and perinatal outcome in pregnancy: observational study

Background: The present study was conducted with the objective to assess the spectrum of liver disease in pregnancy, and its course and effect on maternal and fetal outcomes.Methods: The present study was conducted as a prospective follow up study in the department of Obstetrics and Gynaecology, J. K. Hospital for a period of 1 year. The pregnant women between the ages of 18-35 years presenting with symptoms suggestive of underlying liver disease were selected. Socio demographic details and clinical history was obtained from all the participants and they were subjected to liver function test (LFT). All patients were followed till 2 weeks post-partum period. The maternal and fetal outcomes were noted.Results: The following results were obtained: pregnancy-induced hypertension (PIH) was the most common cause of abnormal LFT (46.66%), about 57.5% patients delivered at term, 63.3% patients delivered vaginally, mostly cases delivered a term healthy neonate between 2.5-3.0 kg weight with Apgar score >7 at 5 minutes after birth and maternal complications were seen in 10.82% cases.Conclusions: Our study shows that though liver disease is uncommon in Indian pregnant women, but it is associated with high maternal and perinatal morbidity. A high index of suspicion of liver disease, early diagnosis, prompt referral to a higher centre when required, appropriate supportive management, and a proactive policy of early delivery when indicated may improve the maternal and fetal outcomes in pregnant women with liver disease. Thus LFT should be conducted as a routine investigation in all pregnant females during first and second trimester

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The toxic tango: TKI and TCI cardiotoxicities

Abstract Background Immune checkpoint inhibitors (ICI) and Tyrosine kinase inhibitors (TKI) are effective for several types of cancers, but they can have several cardiotoxicity sides effects. We present a case of TKI-ICI toxicity resulting in multiorgan inflammatory syndrome with myocarditis and thrombotic STEMI that were successfully treated with high-dose steroids and PCI. Case presentation Seventy-two year-old man patient treated with on pembrolizumab 200 mg IV every 3 weeks and Axitinib 5 mg PO q12h for the past 5 months complained of acute shortness of breath, altered mental status, and chronic diarrhea. Coronary angiography demonstrated a thrombotic lesion in the right coronary artery (RCA) that was treated successfully with percutaneous coronary intervention (PCI). Despite PCI he continued to complain of shortness of breath further workup with Cardiac MRI (CMR) was obtained showed an ejection fraction of 38%, small pericardial effusion, and delayed gadolinium enhancement (DGE) in the inferior wall suggestive of myocarditis. An empirical trial of high-dose steroids improved all patient symptoms and ejection fraction; therefore, the chemotherapy regimen was changed. Conclusion This case report highlights the potential vasculogenic effects of Axitinib and immune-related myocarditis of pembrolizumab. Cardiologists and oncologists should be vigilant for the cardiotoxic effects of Axitinib and pembrolizumab

Rehab-Net: Deep Learning framework for Arm Movement Classification using Wearable Sensors for Stroke Rehabilitation

In this paper, we present a deep learning framework 'Rehab-Net' for effectively classifying three upper limb movements of the human arm, involving extension, flexion and rotation of the forearm which over the time could provide a measure of rehabilitation progress. The proposed framework, Rehab-Net is formulated with a personalized, light weight and low complex, customized CNN model, using 2-layers of Convolutional neural network (CNN), interleaved with pooling layers, followed by a fully-connected layer that classifies the three movements from tri-axial acceleration input data collected from the wrist. The proposed Rehab-net framework was validated on sensor data collected in two situations-a) seminaturalistic environment involving an archetypal activity of 'making-tea' with 4 stroke survivors and b) natural environment, where 10 stroke survivors were free to perform any desired arm movement for a duration of 120 minutes. We achieve an overall accuracy of 97.89% on semi-naturalistic data and 88.87% on naturalistic data which exceeded state-of-the-art learning algorithms namely, Linear Discriminant Analysis, Support Vector Machines, and k-means clustering with an average accuracy of 48.89%, 44.14% and 27.64%. Subsequently, a computational complexity analysis of the proposed model has been discussed with an eye towards hardware implementation. The clinical significance of this study is to accurately monitor the clinical progress of the rehabilitated subjects under the ambulatory settings