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Heidi Chwan Ko,1,* RJ Seager,2,* Sarabjot Pabla,2 Maria-Fernanda Senosain,2 Erik Van Roey,2 Shuang Gao,2 Kyle C Strickland,1,3 Rebecca Ann Previs,1,4 Michelle F Green,1 Maureen Cooper,1 Mary K Nesline,1 Stephanie B Hastings,1 Kobina Agyaful Amoah,1 Shengle Zhang,2 Jeffrey M Conroy,2 Taylor J Jensen,1 Marcia Eisenberg,5 Brian Caveney,5 Eric A Severson,1 Shakti Ramkissoon,1,6 Shipra Gandhi7 1Labcorp Oncology, Durham, NC, USA; 2Labcorp Oncology, Buffalo, NY, USA; 3Department of Pathology, Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA; 4Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA; 5Labcorp, Burlington, NC, USA; 6Department of Pathology, Wake Forest Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA; 7Department of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA*These authors contributed equally to this workCorrespondence: Heidi Chwan Ko, Email Heidi.ko@labcorp.comBackground: The understanding of molecular characteristics of HER2-low breast cancer is evolving since the establishment of trastuzumab deruxtecan. Here, we explore the differences in expression patterns of immune-related genes in the tumor immune microenvironment (TME) and survival between HER2-low and HER2-zero breast cancers.Methods: Comprehensive genomic and immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on FFPE samples from 129 patients with advanced HER2-negative (immunohistochemistry (IHC) 0, 1+ or 2+ with negative ERBB2 amplification by in-situ hybridization) breast cancer. Both estrogen receptor (ER) and HER2 statuses were obtained from available pathology reports. mRNA expressions of immune biomarkers, except for PD-L1 IHC and TMB, were derived from RNA-seq. Statistical comparisons were performed using the Kruskal–Wallis or Wilcoxon Rank-Sum test or the two-sample test for equality of proportions with continuity correction (p≤ 0.05 for significance). Survival differences were calculated using Kaplan-Meier analysis (p≤ 0.05 for significance).Results: There were no significant differences in mRNA expressions of immune-related genes between HER2-low and HER2-zero breast cancers. However, HER2-low breast cancers were associated with a higher proportion of ER-positivity. When ER was analyzed along with HER2, we observed a significantly higher tumor immunogenic signature (TIGS) expression in HER2-zero/ER-negative tumors than in HER2-low/ER-positive tumors (p=0.0088). Similarly, lower expression of PD-L1 and T cell immunoglobulin and ITIM domain (TIGIT) mRNA was observed in HER2-low/ER-positive tumors when compared to HER2-zero/ER-negative tumors (p=0.014 and 0.012, respectively). Patients with HER2-low tumors had a longer median OS than those with HER2-zero tumors (94 months vs 42 months, p=0.0044).Conclusion: Patients with HER2-low breast cancer have longer survivals yet display no differences in immune-related gene expression when compared to those with HER2-zero cancers. The differences in survival can be attributed to the higher rate of ER-positivity seen in HER2-low breast cancers, compared to HER2-zero tumors.Keywords: HER2-low breast cancer, estrogen receptor, tumor immune microenvironment, immune checkpoint biomarkers, gene expression profiling, immune profiling

Background The Scientific Registry for Transplant Recipients (SRTR) publishes outcomes of all transplant centres in the USA two times a year. The outcomes are publicly available and used by insurance payers and patients to assess the performance of a programme. Poor performance can result in temporary suspension or termination of a transplant programme. The estimated 1-year survival hazard ratio (EHR) is an important metric publicly reported by the SRTR.Problem The EHR at our institution was 1.13, indicating a graft loss rate that was 13% higher than the national average.Methods/INTERVENTION We defined an improvement in this metric as achieving an EHR of

This article seeks to highlight an aspect of the illegal pharmaceutical trade in the Caribbean. With the advent of COVID-19 there has been a shortage of a number of drugs in the formal sector. This is largely due to restrictions on foreign exchange, importation delays and sensationalized reporting of unrecommended drugs having a curative effect on COVID-19 patients. This article examines the issue of “the informal suitcase trading” of these drugs. It posits a need for a collaborative and multi-sectoral approach to mitigate the negative effects of the practice on health, trade and national security.

IntroductionMatching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics.MethodsIn this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC.ResultsTesting revealed distinct genomic profiles of lung adenocarcinoma and squamous cell carcinomas and detected variants with a current targeted therapy or clinical trial in >72% of patient tumors. Known associations between genomic alterations and immunotherapy markers were observed including significantly lower TMB levels in tumors with therapy-associated alterations and significantly higher PD-L1 levels in tumors with ALK, MET, BRAF, or ROS1 driver mutations. Co-occurrence analysis followed by network analysis with gene module detection revealed known and novel co-occurrences between genomic alterations. Further, certain modules of genes with co-occurring genomic alterations had dose-dependent relationships with histology and increasing or decreasing levels of PD-L1 and TMB, suggesting a complex relationship between PD-L1, TMB, and genomic alterations in these gene modules.DiscussionThis study is the largest clinical study to date utilizing the TSO 500. It provides an opportunity to further characterize the landscape of NSCLC using this newer technology and show its clinical utility in detecting known and novel facets of NSCLC to inform treatment decision-making.

Clinical management of non-small cell lung cancer (NSCLC) requires accurate identification of tumor-specific genetic alterations to inform treatment options. Historically, providers have relied on single-gene testing (SGT) for actionable variants due to a perception of cost-effectiveness and/or efficient turnaround time compared to next-generation sequencing (NGS). However, not all actionable variants may be evaluated through SGT modalities, and an SGT approach can exhaust valuable tissue needed for more comprehensive analyses. In contrast, comprehensive genomic profiling (CGP) tests employ NGS to sequence megabases of DNA and RNA to evaluate all relevant molecular alterations, providing a broader genetic profile to identify actionable alterations that SGT may not accurately or efficiently assess. Here, we briefly describe four cases from a large reference laboratory in which actionable alterations were identified by CGP but not SGT. The discussion highlights the utility and advantages of using CGP to provide complete and timely treatment options and clinical trial opportunities for patients with NSCLC.

Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic disorder that develops in patients exposed to heparin products. Diagnosis is associated with significant morbidity and mortality. The mainstay of treatment for HIT involves discontinuing all heparin products and administering non-heparin anticoagulants. Since the publication of the American Society of Hematology (ASH) guidelines in 2018, factor Xa inhibitors have become an attractive alternative. We systematically reviewed the literature to determine the efficacy and safety of factor Xa inhibitors in managing HIT. We included any case series, retrospective, or prospective study that evaluated the efficacy of factor Xa inhibitors. We searched PubMed, Ovid, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar from inception to September 2023. Three reviewers independently reviewed titles, abstracts, and full-text articles to determine eligibility using prespecified inclusion and exclusion criteria. Disagreements were resolved by discussion and consensus. Nine hundred sixty-four articles were screened against title and abstract, and 75 studies were selected for full-text review. Fifteen studies eventually met the inclusion criteria. Two hundred eighty-five patients across 15 studies were treated with factor Xa inhibitor. Across all study arms combined, HIT thrombosis-associated mortality was 0 % (n = 0), recurrent thrombosis was 4.56 % (n = 13), and major bleeding was 2.80 % (n = 8). Factor Xa inhibitors showed positive outcomes in HIT in terms of both safety and efficacy. Major limitation of this review is that the studies included are primarily retrospective and, thus, are subject to inherent limitations of observational study design. More randomized controlled trials (RCT) or prospective studies examining non-inferiority or superiority of transitioning to direct oral anticoagulant (DOAC) vs primary treatment with DOAC are needed.

With the advent of e-learning, advocates use the term interactivity instead of interaction among students, and between the teacher and the students. Many universities use Moodle for online teaching and learning. This paper explores the perceptions and experiences of students in three Higher Education Institutions (HEIs) in Mauritius. A mixed-methods approach was used, with an online survey questionnaire administered to 600 students and focus group discussions were conducted with 15 students from these institutions. It was found that 68.4% of respondents used WhatsApp compared to only 23.6% of them who used the e-learning platform, Moodle. There were no associations between the use or frequency of using WhatsApp or Facebook and the types of HEI to which the students belonged. Students preferred WhatsApp due to its facility for knowledge sharing and construction, its interactivity, its usability, respect for privacy and instant communication. From the findings, it is recommended that HEIs bring a shift in their approaches to teaching and learning from cognitivism to socio-constructivism, connectivism and heutagogy.

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.

IntroductionYounger patients with non-small cell lung cancer (NSCLC) (

There is an emerging view that remittances improve health outcomes in developing countries, though less is known about the conditions under which they may be effective. This study investigates whether and how the impact of remittances on child mortality depends on the level of mortality itself. Using a sample of 134 developing countries over the period 1990 to 2018, we estimate unconditional quantile treatment effects with an endogenous treatment variable, on aggregate child mortality and the three leading cause-specific child mortality rates: mortality from neonatal disorders, lower respiratory infections, and diarrheal diseases. We find that the impact of remittances differs systematically across the mortality distribution and across mortality indicators. Remittances appear less effective at reducing child mortality at the lowest and highest mortality rates than at the average.

BackgroundRecommendations in clinical practice guidelines (CPGs) may be reversed when evidence emerges to show they are futile or unsafe. In this study, we identified and characterized recommendation reversals in gastroenterology CPGs.MethodsWe searched CPGs published by 20 gastroenterology societies from January 1990 to December 2019. We included guidelines which had at least two iterations of the same topic. We defined reversals as when (a) the more recent iteration of a CPG recommends against a specific practice that was previously recommend in an earlier iteration of a CPG from the same body, and (b) the recommendation in the previous iteration of the CPG is not replaced by a new diagnostic or therapeutic recommendation in the more recent iteration of the CPG. The primary outcome was the number of recommendation reversals. Secondary outcomes included the strength of recommendations and quality of evidence cited for reversals.ResultsTwenty societies published 1022 CPGs from 1990 to 2019. Our sample for analysis included 129 unique CPGs. There were 11 recommendation reversals from 10 guidelines. New evidence was presented for 10 recommendation reversals. Meta-analyses were cited for two reversals, and randomized controlled trials (RCTs) for seven reversals. Recommendations were stronger after the reversal for three cases, weaker in two cases, and of similar strength in three cases. We were unable to compare recommendation strengths for three reversals.ConclusionRecommendation reversals in gastroenterology CPGs are uncommon but highlight low value or harmful practices.

* Context.--Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear. Objective.--To examine the prevalence of molecular testing for clinically relevant biomarkers in adult and pediatric gliomas through review of a College of American Pathologists proficiency testing survey prior to the release of the 2021 World Health Organization Classification of Central Nervous System Tumors. Design.--College of American Pathologists proficiency testing 2020 survey results from 96 laboratories performing molecular testing for diffuse gliomas were used to determine the use of testing for molecular biomarkers in gliomas. Results.--The data provide perspective into the testing practices for diffuse gliomas from a broad group of clinical laboratories in 2020. More than 98% of participating laboratories perform testing for glioma biomarkers recognized as diagnostic for specific subtypes, including IDH. More than 60% of laboratories also use molecular markers to differentiate between astrocytic and oligodendroglial lineage tumors, with some laboratories providing more comprehensive analyses, including prognostic biomarkers, such as CDKN2A/B homozygous deletions. Almost all laboratories test for MGMT promoter methylation to identify patients with an increased likelihood of responding to temozolomide. Conclusions.--These findings highlight the state of molecular testing in 2020 for the diagnosis and classification of diffuse gliomas at large academic medical centers. The findings show that comprehensive molecular testing is not universal across clinical laboratories and highlight the gaps between laboratory practices in 2020 and the recommendations in the 2021 World Health Organization Classification of Central Nervous System Tumors. doi: 10.5858/arpa.2021-0431-CP, Historically, the classification of diffuse gliomas was based in large part on histologic features, including tumor cell morphology, mitotic index, and the presence of necrosis and/or microvascular proliferation. To delineate [...]

Context.--Multiple procedural techniques can be used to obtain tissue to create a formalin-fixed, paraffin-embedded specimen for comprehensive genomic profiling (CGP) in lung cancer. The literature is mixed on whether the procedure affects CGP success. Objective.--To examine whether biopsy procedure affects lung cancer CGP success. Design.--This was a cross-sectional study of all patients with lung cancer whose specimens were submitted for CGP between January and February 2020. Multiple quality control metrics were used to determine whether cases were successfully profiled. Results.--In all, 3312 samples were identified. Overall, 67.5% (2236 of 3312) of samples were obtained from biopsies, 13.0% (432 of 3312) from fine-needle aspirations (FNAs), 9.7% (321 of 3312) from resections, 5.3% (174 of 3312) from fluid cytology cell blocks, and 4.5% (149 of 3312) from bone biopsies. Overall, 70.1% (2321 of 3312) of cases passed CGP, 15.4% (510 of 3312) of cases were released as qualified reports, and 14.5% (481 of 3312) of cases failed CGP. Resection samples were the most likely to be successfully sequenced, failing in only 2.8% (9 of 321) of instances, while fluid cytology specimens were the least likely, failing in 23.0% (40 of 174) of instances. Biopsy (14.5% [324 of 2236]), FNA (18.5% [80 of 432]), and bone biopsy (18.8% [28 of 149]) specimens failed at intermediate frequencies. On multivariate logistic regression analysis of CGP success on specimen type, fluid cytology (odds ratio [OR], 0.08; 95% CI, 0.03-0.19), biopsy (OR, 0.25; 95% CI, 0.11-0.52), FNA (OR, 0.14; 95% CI, 0.06-0.32), and bone biopsy (OR, 0.07; 95% CI, 0.03-0.17) specimens had decreased odds of CGP success relative to resection samples. Among patients with successfully sequenced samples, 48.0% were eligible for at least 1 therapy, based on a companion diagnostic or National Comprehensive Cancer Network biomarker. Conclusions.--The method of tissue acquisition was an important preanalytic factor that determined whether a sample would be successfully sequenced and whether a clinically actionable genomic alteration would be detected. doi: 10.5858/arpa.2021-0313-OA, In 2020, lung cancer was the tumor type with the highest mortality, with 1.8 million deaths worldwide. (1) The most common type of lung cancer is non-small cell lung carcinoma [...]