MET amplification (METamp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome METamp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter Phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, determined centrally by fluorescence in situ hybridization (gene copy number ≥5 and/or MET/CEP7 ≥2) at time of progression. Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once-a-day. The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov)

Abstract. Co-infection of melioidosis and leptospirosis is uncommon. We report here four such cases, confirmed by blood culture for melioidosis and blood polymerase-chain reaction for leptospirosis, which occurred among rescuers involved in a search and rescue operation for a young man who was suspected to have drowned in Lubuk Yu, a recreational forest in Pahang, Malaysia. Despite treatment, three of the patients died from the co-infection.

Cancer-associated thrombosis (CAT) is a leading cause of death in cancer patients receiving outpatient chemotherapy. The latest guidelines emphasize stratifying the patients in terms of CAT risks periodically. Multiple risk assessment models (RAMs) were developed to classify patients and guide thromboprophylaxis to high-risk patients. This study aimed to discuss and highlight different RAMs across various malignancy types with their related advantages and disadvantages. A scoping review was conducted using predefined search terms in three scientific databases, including Google Scholar, Science Direct, and PubMed. The search for studies was restricted to original research articles that reported risk assessment models published in the last thirteen years (between 2008 and 2021) to cover the most recently published evidence following the development of the principal risk assessment score in 2008. Data charting of the relevant trials, scores, advantages, and disadvantages were done iteratively considering the malignancy type. Of the initially identified 1115 studies, 39 studies with over 67,680 patients were included in the review. In solid organ malignancy, nine risk assessment scores were generated. The first and most known Khorana risk score still offers the best available risk assessment model when used for high-risk populations with a threshold of 2 and above. However, KRS has a limitation of failure to stratify low-risk patients. The COMPASS-CAT score showed the best performance in the lung carcinoma patients who have a higher prevalence of thrombosis than other malignancy subtypes. In testicular germ cell tumours, Bezan et al RAM is a validated good discriminatory RAM for this malignancy subtype. CAT in haematological malignancy seems to be under-investigated and has multiple disease-related, and treatment-related confounding factors. AL-Ani et al score performed efficiently in acute leukemia. In multiple myeloma, both SAVED and IMPEDED VTE scores showed good performance. Despite the availability of different disease-specific scores in lymphoma-related thrombosis, the standard of care needs to be redefined.

SARS-CoV-2 has spread throughout the world since its discovery in China, and Malaysia is no exception. WGS has been a crucial approach in studying the evolution and genetic diversity of SARS-CoV-2 in the ongoing pandemic. Despite considerable number of SARS-CoV-2 genome sequences have been submitted to GISAID and NCBI databases, there is still scarcity of data from Malaysia. This study aims to report new Malaysian lineages of the virus, responsible for the sustained spikes in COVID-19 cases during the third wave of the pandemic. Patients with nasopharyngeal and/or oropharyngeal swabs confirmed COVID-19 positive by real-time RT-PCR with CT value < 25 were chosen for WGS. The selected SARS-CoV-2 isolates were then sequenced, characterized and analyzed along with 986 sequences of the dominant lineages of D614G variants currently circulating throughout Malaysia. The prevalence of clade GH and G formed strong ground for the presence of two Malaysian lineages of AU.2 and B.1.524 that has caused sustained spikes of cases in the country. Statistical analysis on the association of gender and age group with Malaysian lineages revealed a significant association (p <0.05). Phylogenetic analysis revealed dispersion of 41 lineages, of these, 22 lineages are still active. Mutational analysis showed presence of unique G1223C missense mutation in transmembrane domain of the spike protein. For better understanding of the SARS-CoV-2 evolution in Malaysia especially with reference to the reported lineages, large scale studies based on WGS are warranted.

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