Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

At present, the main therapies for ß-thalassemia patients include regular blood transfusion and iron chelation, associating with a number of limitations. Thalidomide, a fetal hemoglobin (HbF) inducer that promotes γ-globin gene expression, has been reported to be effective for ß-thalassemia. Thus, this meta-analysis was conducted to assess the efficacy and safety of thalidomide for treating patients with ß-thalassemia. We searched the related studies from eight databases published from inception until December 1, 2021. The R 4.0.5 language programming was used to perform meta-analysis. After screening of retrieved articles, 12 articles were included that enrolled a total of 451 patients. The Cochrane Collaboration risk assessment tool was used to evaluate the quality and the bias risk of the randomized controlled trials (RCTs), and non randomized trials were assessed using Newcastle-Ottawa Scale (NOS). After treatment with thalidomide, the pooled overall response rate (ORR) was 85% (95% confidence interval (CI): 80–90%), and the pooled complete response rate (CRR) was 54% (95% confidence interval: 31–76%). Compared with the placebo group, the thalidomide group had higher odds of overall response rate (odds ratio = 20.4; 95% CI: 6.75–61.64) and complete response rate (odds ratio = 20.4; 95% CI: 6.75–61.64). A statistically significant increase in hemoglobin level and HbF level after treatment, while there was no statistically significant difference in adult hemoglobin (HbA) level, spleen size, and serum ferritin. According to the results of ORR and CRR, transfusion-dependent thalassemia (TDT) patients showed remarkable efficacy of thalidomide, 83 and 52% respectively. So we analyzed 30 transfusion-dependent thalassemia patients from three studies and found that the most frequent ß-globin gene mutations were CD41-42 (-TCTT), while response to thalidomide did not show any statistically significant relationship with XmnI polymorphism or CD41-42 (-TCTT) mutation. About 30% of patients experienced mild adverse effects of thalidomide. Collectively, thalidomide is a relatively safe and effective therapy to reduce the blood transfusion requirements and to increase Hb level in patients with ß-thalassemia.

CONSIDERATION AND UTILIZE OF LIBRARY WEB RESOURCES BY FACULTY OF ENGINEERING COLLEGE IN EAST GODAVARI DISTRICT, ANDHRA PRADESH: A STUDY

Digital information resources are fetching more and more imperative for the academic community. The increase of technical colleges in Andhra Pradesh are quiet noteworthy and in advance of various states of India. Digital resources are measured as imperative resources of teaching, research and training. Consequently, digital resources play a important role in academic libraries as they are mostly jingle for the support of academic brilliancy and research. For these research questionnaires were distributed to the faculty members of 10 selected engineering colleges in East Godavari district of Andhra Pradesh. Accordingly, 400 questionnaire distributed amongst the faculty members of 10 engineering colleges. Out of 400, only 336 questionnaires were received back that is the overall response rate is 84%.. 27.98% of the faculties are utilize digital resources for bring up to date Knowledge. It is also found from the study that preponderance of the faculty members were satisfied with available digital resources.

Stereotactic Radiation and Dual Human Epidermal Growth Factor Receptor 2 Blockade with Trastuzumab and Pertuzumab in the Treatment of Breast Cancer Brain Metastases: A Single Institution Series

(1) Background: This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and pertuzumab–trastuzumab (PT) in patients with breast cancer brain metastases (BCBM). (2) Methods: Patients with HER2+ BCBM who received FSRT from 2015 to 2019 were identified. Patients were included if they were treated with fSRT within 21 days of receiving PT. All lesions were treated with LINAC-based fSRT to a total dose of 27 Gy delivered in three consecutive fractions. All patients received concurrent PT. Patients were evaluated 4–6 weeks after SRS and subsequently every 2–3 months with MRI re-imaging (3) Results: A total of 49 patients with HER2+ brain metastases were identified. Of these patients, a total of 10 patients with 32 HER2+ BCBM were treated with concurrent SRT and PT and included in the analysis. No local progression was observed. Overall response rate was 68.7%. Only one patient developed asymptomatic radionecrosis. Median time to BM occurrence was 15.6 (range: 1–40.5 months). Distant intracranial failure occurred in 4/10 patients (40.0%). Overall BCBM median survival was 33.9 months (95%CI 24.1–43.6). Mean duration of PT treatment was 27.9 months (range: 10.1–53.7 months). (4) Conclusions: In our single institution experience, fSRT and PT showed to be a safe treatment for patients with BCBM with an adequate overall response rate.

FOLFIRINOX as First-line Chemotherapy in Japanese Patients Suffering from Metastatic Pancreatic Cancer (KOBE FOLFIRINOX Study)

Background/Aim: FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin) combination chemotherapy is the gold-standard therapy for advanced pancreatic cancer. In this study, FOLFIRINOX dosages for Japanese patients were established enabling FOLFIRINOX therapy optimization for efficient use. Patients and Methods: Patients with advanced pancreatic cancer were treated with varying doses of FOLFIRINOX to determine the optimum dosage for highest remission outcomes with the least post-chemotherapy toxicities. Results: Patients given 180 mg of irinotecan and a 400 mg bolus of 5-fluorouracil (5-FU) showed a marked difference in outcome when compared to irinotecan 180 mg given without the 5-FU bolus, with the overall response rate being 28%, a survival time of 6.4 months and progression-free survival time of 4.5 months. Conclusion: The optimum dose of FOLFIRINOX was a dosage combination of oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, l-leucovorin 400 mg/m2 and 5-FU 2,400 mg/m2, administered as a continuous 46-h infusion.

Percutaneous Hepatic Perfusion (PHP) with Melphalan in Liver-Dominant Metastatic Uveal Melanoma: The German Experience

Percutaneous hepatic perfusion (PHP) delivers high-dose melphalan to the liver while minimizing systemic toxicity via filtration of the venous hepatic blood. This two-center study aimed to examine the safety, response to therapy, and survival of patients with hepatic-dominant metastatic uveal melanoma (UM) treated with PHP. A total of 66 patients with liver-dominant metastasized uveal melanoma, treated with 145 PHP between April 2014 and May 2020, were retrospectively analyzed with regard to adverse events (AEs; CTCAE v5.0), response (overall response rate (ORR)), and disease control rate (DCR) according to RECIST1.1, as well as progression-free and overall survival (PFS and OS). With an ORR of 59% and a DCR of 93.4%, the response was encouraging. After initial PHP, median hepatic PFS was 12.4 (confidence interval (CI) 4–18.4) months and median OS was 18.4 (CI 7–24.6) months. Hematologic toxicity was the most frequent AE (grade 3 or 4 thrombocytopenia after 24.8% of the procedures); less frequent was grade 3 or 4 hepatic toxicity (increased aspartate transaminase (AST) and alanine transaminase (ALT) after 7.6% and 6.9% of the interventions, respectively). Cardiovascular events included four cases of ischemic stroke (2.8%) and one patient with central pulmonary embolism (0.7%). In conclusion, PHP is a safe and effective salvage treatment for liver-dominant metastatic uveal melanoma. Serious AEs—though rare—demand careful patient selection.

TACE Plus Lenvatinib Versus TACE Plus Sorafenib for Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Prospective Cohort Study

Background and ObjectivesThis study aimed to compare the efficacy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S) to TACE plus lenvatinib (TACE-L) for the treatment of HCC with portal vein tumor thrombus (PVTT).MethodsThis cohort study recruited patients from September 2017 to September 2020. A total of 59 and 57 consecutive patients were treated with TACE-L and TACE-S, respectively.ResultsBefore propensity score matching (PSM), comparing TACE-L to TACE-S, the median overall survival (OS) time was 16.4 months and 12.7 months, respectively [hazard ratio (HR) 1.34; 95% confidence interval (CI): 0.81–2.20; p = 0.25]. The median progression-free survival (PFS) time was 8.4 months and 7.43 months, respectively (HR 1.54; 95% CI: 0.98–2.41; p = 0.081). After PSM, the median OS time was 18.97 months and 10.77 months, respectively (HR 2.21; 95% CI: 1.12–4.38; p = 0.022); the median PFS time was 10.6 months (95% CI: 6.6–18.0 months) and 5.4 months (95% CI: 4.2–8.1 months), respectively (HR 2.62; 95% CI: 1.43–4.80; p = 0.002). After PSM, the overall response rate (ORR) was 66.8% vs. 33.3% [odds ratio (OR) 0.85; 1.05–6.90; p = 0.037].ConclusionBoth TACE-L and TACE-S are safe, well-tolerated treatments for HCC with PVTT. In HCC with PVTT, TACE-L was significantly superior to TACE-S with respect to OS, PFS, and ORR. A larger-scale randomized clinical trial is needed.

Effect of Prior Antibiotic or Chemotherapy Treatment on Immunotherapy Response in Non-small Cell Lung Cancer

Background Treatment outcomes of advanced non-small cell lung cancer (NSCLC) have substantially improved with immune checkpoint inhibitors (ICI), although only approximately 19% of patients respond to immunotherapy alone, increasing to 58% with the addition of chemotherapy. The gut microbiome has been recognized as a modulator of ICI response via its priming effect on the host immune response. Antibiotics as well as chemotherapy reduce gut microbial diversity, hence altering composition and function of the gut microbiome. Since the gut microbiome may modify ICI efficacy, we conducted a retrospective study evaluating the effects of prior antibiotic or chemotherapy use on NSCLC patient response to ICI.Methods We retrospectively evaluated 256 NSCLC patients treated between 2011-2017 at Moffitt Cancer Center with ICI ± chemotherapy, examining the associations between prior antibiotic or chemotherapy use, overall response rate and survival. Relative risk regression using a log-link with combinatorial expectation maximization algorithm was performed to analyze differences in response between patients treated with antibiotics or chemotherapy versus patients who didn’t receive antibiotics or chemotherapy. Cox proportional hazards models were constructed to evaluate associations between risk factors and overall survival. Results Only 46 (18% of 256) patients used antibiotics prior to and/or during ICI treatment, and 146 (57%) had prior chemotherapy. Antibiotic users were 8% more likely to have worse overall response rate (RR:1.08; CI:0.93-1.26; p=0.321), as well as a 35% worse overall survival (HR:1.35; CI:0.91-2.02; p=0.145), although results were not statistically significant. However, prior use of chemotherapy was significantly associated with poor ICI response (RR:1.24; CI:1.05-1.47; p=0.013) and worse overall survival (HR:1.47; CI:1.07-2.03; p=0.018). Conclusions Patients receiving antibiotics prior to and/or during ICI therapy might experience worse treatment outcomes and survival than unexposed patients, although these associations were not statistically significant and hence warrant further prospective study. Prior chemotherapy significantly reduced ICI response and overall survival. Antibiotic or chemotherapy exposure may negatively impact ICI response, perhaps through disruption of the eubiotic gut microbiome.

Perception of Dental Students towards the usage of Online Assessment during COVID -19 Pandemic

Background: The COVID-19 pandemic have forced educational institutions to shift rapidly to distance and online learning. This study aims to explore attitude and perception of dental students towards online assessment during pandemic. Objective: To assess student’s perception, attitudes, and readiness toward online assessment. Methodology: A self constructed questionnaire including 10 questions was designed with 5 specialists, to improve the design ambiguity. The study was conducted through electronic media. Results: A total of 270 dental students answered the survey. The overall response rate was 70.68%. More than 50% students are well versed with online assessment. One fourth of the participants found convenience as the advantage while 64.7% students encountered technical issue as the limitation of online assessment. There was overall positive attitude towards usage of online assessment. Conclusions: This study showed acceptable levels of individual characteristics and system ability levels as well as the perceived importance of using online tools in dental education among the participants.

Does Early Neonatal Thrombocytopenia Affect Ductal Therapeutic Respose to Acetaminophen in Preterm Neonates?

Perinatal thrombocytopenia has been shown to affect responsiveness to therapeutic ductal closure with cyclo-oxygenase inhibitors. This has not been studied in responsiveness to acetaminophen, which has less effect on platelet function. Objective: To evaluate whether thrombocytopenia affects ductal responsiveness to acetaminophen. Study Design: Retrospective review of preterm neonates <1500 gm. Echocardiograms were performed within the first week of life; if ductal status was found to be hemodynamically significant, infants were treated with acetaminophen. Results: We studied 254 infants. Fifty seven of these (22%) had a hemodynamically significant PDA (hsPDA) and were treated with acetaminophen. Forty (70%) of those treated responded with ductal closure after 1-2 courses of acetaminophen. Seventeen infants were considered non-responsive, requiring the addition of ibuprofen and/or surgical ligation. Sixty-seven of the 254 infants (26%) developed moderate thrombocytopenia [platelets <100,000] within the first ten days of life, more within the hsPDA group (54% vs. 18% p<0.001); however, no differences in platelet related parameters were observed when comparing infants with hsPDA who did or did not respond to acetaminophen treatment. Twenty-six of the 67 thrombocytopenic were already thrombocytopenic prior to acetaminophen treatment; and 19 of these 26 (73%) with pre-treatment thrombocytopenia responded to acetaminophen treatment – similar to the overall response rate of 70% . Conclusions: This study is the first to document that, in contrast to the cyclo-oxygenase inhibitors, there is no association between early neonatal thrombocytopenia and ductal therapeutic responsiveness to acetaminophen.

Demystifying performance difference between local and foreign contractors through organisational culture

PurposeThis research aimed to investigate the extent to which organisational culture is practised in local and foreign contractors in grade one and two categories and how it affects their performance.Design/methodology/approachThe approach for this research was positivist in nature adopting a mono-method of data collection through a survey using self-administered questionnaires. A total of 138 questionnaires were distributed among public clients and large-scale contractors registered in the stated grades, and 112 questionnaires were returned for analysis representing an overall response rate of 81% for contractors and clients.FindingsFindings revealed that in organisational culture, significant differences were found for management style and dominant characteristics of the organisation between local and foreign contractors. Differences were not found for leadership styles, measures of success and organisational glue. Results suggest that for local contractors to perform better, significant changes are needed to their management style and dominant characteristics of their organisations.Originality/valueForeign contractors in the Zambian construction industry are reportedly outperforming local contractors making them preferred contractors on larger public projects accounting for 85% of construction projects by value of works. This study presents the differences in organisational culture between foreign and local firms. It further demonstrates that organisational culture plays a key role in determining performance of a contracting firm. The study presents areas that local contractors can improve in organisational culture in order to remain competitive.