Insights into the medical management of gastrointestinal stromal tumours: lessons learnt from a dedicated gastrointestinal stromal tumour clinic in North India.

Background: The advent of molecular driver alterations has brought in a revolutionary transformation in the treatment landscape of gastrointestinal stromal tumour (GIST). However, there is a paucity of data regarding mutational testing prevalence and associated outcomes from India. Methods: It was a retrospective study. We reviewed the case records of all patients diagnosed with GIST in a tertiary care centre from 2015 to 2021. The clinicopathological, mutational analysis and treatment plans were recorded. The study cohort was characterised by descriptive statistics. Results: Our study included 120 patients with a median age of 53 years (range: 28-77), with a male preponderance of 2:1. The most common site of the primary was the stomach (50%), followed by the small intestine (37%), with 55.8% of the patients having disseminated disease at presentation with a predominance of liver metastasis (67%). The prevalence of mutational analysis among patients prior to referral was 4%. 60.8% of the patients at our clinic had mutational analysis performed, and unavailability of analysis in the rest was due to financial constraints (12.5%), exhaustion of tissue (7.5%), reluctance to repeat biopsy (4.1%) and low-risk patients. We report c-kit in the majority (52%), platelet-derived growth factor receptor (PDGFR) in 19.2% and wild type in 16.4% along with the rarer subtypes: succinate dehydrogenase (SDH)-deficient GIST in 10.9% and Neurotrophic tyrosine receptor kinase (NTRK) fusion in 1.3%. Four of the eight SDH-deficient GIST patients had germline mutations (50%). The knowledge of driver mutations led to a change of treatment in 39.7% (29/73), i.e. stoppage of tyrosine kinase inhibitor (TKI) in 3, switch of TKI in 23, increase in TKI dose in 2 and upfront surgery in 1. The most common change was the use of sunitinib and regorafenib in patients with SDH-deficient GIST. Conclusion: Our study is one of the largest comprehensive series describing the clinical and mutational profile of GIST from India. The mutation testing rates at primary care centres continue to be low. Despite the hurdles, a large percentage of our patients underwent molecular testing, aiding in therapeutic decision-making.

Utility of quick sepsis-related organ failure assessment (qSOFA) score to predict outcomes in out-of-ICU patients with suspected infections.

BACKGROUND: Referral of sepsis patients at the level of primary care is often delayed due to the lack of an assessment tool which effectively predicts sepsis. The quick Sepsis-related Organ Failure Assessment score (qSOFA) can be used in such scenarios to improve patient outcomes. AIM: To assess the prognostic accuracy of qSOFA score in predicting adverse outcomes in patients with suspected infections and to compare it with the SIRS (Systemic Inflammatory Response Syndrome) and the SOFA (Sequential Organ failure Assessment Score). METHODS: This study included 180 participants admitted in the emergency wards of the Department of Medicine, over a period of one year with suspected infection. The primary outcome was the combined outcome of mortality and/or ICU stay of more than three days. Secondary outcomes were the duration of ICU stay, duration of inotrope use, and duration of mechanical ventilation. STATISTICAL ANALYSIS: Descriptive statistics using SPSS version 19.0 was applied in the study. RESULTS: Of the 180 participants, 54 had a qSOFA score of 2 at admission, 52 participants had an SIRS score of 2. The qSOFA score had the highest AUC for both mortality and the combined outcome of mortality and prolonged ICU stay (0.740 and 0.835, respectively). For a combined outcome of mortality and ICU stay >3 days, the qSOFA score had a sensitivity of 75% and a specificity of 82%. The positive likelihood ratio was 4.17. CONCLUSION: In a primary care setting, the qSOFA score of more than 2 can be used reliably to refer patients for admission and intensive care as they are likely to need longer hospital stay and can have worse outcomes.

Drug resistance & virulence determinants in clinical isolates of Enterococcus species.

BACKGROUND & OBJECTIVES: Enterococci are the leading cause of nosocomial infections, and are thus a persisting clinical problem globally. We undertook this study to determine the virulence factors and the antibiotic resistance in Enterococcus clinical isolates. METHODS: One hundred and fifty Enterococcus isolates obtained from various clinical specimens were speciated biochemically and subjected to antibiotic susceptibility testing using Kirby-Bauer disk diffusion method. Resistance to vancomycin was determined by using agar screen method. Haemolysin and gelatinase productions were detected using 5 per cent sheep blood agar and 12 per cent gelatin agar, respectively. RESULTS: Among the 150 Enterococcus isolates, 84 (56%) were E. faecalis. 51(34%) E. faecium, and 15 (10%) were other Enterococcus spp. Haemolysin production was seen among 123 (82%) isolates while 61 (40.6%) isolates produced gelatinase. Nearly 50 per cent of the isolates showed high level aminoglycoside resistance (HLAR). A total of 13 (8.6%) isolates showed vancomycin resistance, of which 11(7.3%) had an MIC >8 µg/ml. INTERPRETATION & CONCLUSIONS: Presence of VRE was found to be low among the isolates studied. However, occurrence of VRE along with HLAR calls for regular detection of vancomycin resistance promptly and accurately to recognize VRE colonization and infection. Early detection of VRE and HLAR along with their virulence trait will help in preventing the establishment and spread of multidrug resistant Enterococcus species.