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Abstract Pulmonary sequestration and cystic pulmonary adenomatoid malformation are rare congenital cystic disorders of the lungs. The presence of both the diseases in the same individual is therefore very uncommon. Pulmonary sequestration is a nonfunctional pulmonary tissue mass that derives its blood supply from systemic blood supply other than pulmonary circulation. Congenital cystic pulmonary adenomatoid malformation represents a mass consisting of abnormal bronchiolar air spaces and a deficiency of functional alveoli. This is the case report of a 9-year-old girl with intermittent fever, left-sided chest pain, and cough for the past 15 days along with recurrent coughs since childhood suggestive of hybrid pulmonary sequestration, congenital cystic adenomatoid malformation, and dextrocardia.

Obstructive Sleep Apnea (OSA) is a condition that obstructs the upper airway during sleep, inducing intermittent hypoxia that affects the host metabolism, and is associated with gut microbiome dysbiosis. The bidirectional link between host immunometabolism and the cardiovascular system connects with the gut microbiome and has emerged as a research interest in recent years. The gut microbiota is recognized as a potential contributor of OSA related comorbidities, including cardiovascular risk. Recent studies have demonstrated that alterations in gut microbial composition are associated with OSA and intermittent hypoxia. Remarkably, the gut-derived metabolite trimethylamine N-oxide (TMAO) has emerged as a putative metabolic link in OSA-associated cardiometabolic risk. In case of OSA, the dysregulated gut metabolic axis may elevate TMAO, which may contribute to endothelial dysfunction and cardiovascular risk. Interestingly, experimental studies suggest that hepatic flavin-containing monooxygenase 3 (FMO3), which catalyzes TMAO production, may be influenced by hypoxia-responsive metabolic pathways, raising the possibility that OSA could affect not only the gut microbiome but also host enzymatic regulation. This perspective will enhance and promote gut microbial-based sleep research, particularly targeted TMAO for the potential risk assessment and as a cardiometabolic marker in OSA. We propose that TMAO may hold potential as a cardiometabolic biomarker in OSA, warranting further validation.

The data on outcomes and toxicity in adult Ewing sarcoma (ES) patients, particularly those aged ≥40 years, is exceedingly scarce around the world, particularly in low- and middle-income countries (LMICs) and mandates research. The study involved histologically ascertained ES patients aged ≥40 years who registered at our institute from 2013 to 2018. Prospectively collected data were analysed for overall survival (OS), event-free survival (EFS) and chemotherapy-related toxicities. There were 66 patients, of which 34 were non-metastatic, and 32 were denovo metastatic, recurrent or had doubtful metastasis. At presentation, median age was 46 years, and 42 (63.6%) had extra-skeletal primary and 24 (36.3%) had extremity tumours. Curative treatment was offered to 40 (60.6%) patients. Significant grade 3/4 toxicities in non-metastatic and metastatic cohort, respectively, were febrile neutropenia (61.3%, 37.5%), anaemia (58.1%, 37.5%), thrombocytopenia (45.2%, 25.0%), peripheral neuropathy (25.8%, 12.5%) and dyselectrolytemia (25.8%, 6.25%). Chemotherapy-related toxicity led to death in three patients in the metastatic cohort, versus none in the non-metastatic patients. The 5 year EFS and OS for non-metastatic cohort were 53.8% and 67.8%, while the same for metastatic cohort were 20.7% and 27.5%, respectively. On multivariate analysis, Eastern Cooperative Oncology Group-performance status >2 and metastasis at presentation predicted poorer EFS and OS. Additionally, raised lactate dehydrogenase, larger tumours (>8 cm) and palliative intent treatment predicted worse EFS, while extra-skeletal primary and female gender were indicators of worse OS. Older adult ES patients benefit from aggressive multimodality treatment even in LMIC infrastructure. However, careful patient selection, close monitoring and pertinent dose modifications is imperative due to higher propensity for potential toxicities.

Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13–75 years with an Eastern Cooperative Oncology Group performance status of 0–2, who were receiving doxorubicin–cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0–120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference –1·0% [one-sided 95% CI –100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. Progressive Ladies Welfare Association.

Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer. The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I–III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306. Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7–12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53–0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61–18·17] with RRM vs 16·65 years [16·38–16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48–0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43–18·03] with RRSO vs 16·67 years [16·38–16·96] without RRSO). In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies. Italian Association for Cancer Research.

The harmful effects of the broad–spectrum, non–selective herbicide glyphosate on the cytological and physiological aspects of Vigna mungo variety Uttara (IPU-94-1) were studied. Water–soaked seeds were grown in the research field of the Botany Department, University of Lucknow. Twenty-one day old plants were treated with varying concentrations of glyphosate: 0 mM, 1 mM, 2 mM, 4 mM, 6 mM, and 8 mM as a foliar spray using a calibrated sprayer to ensure the uniform droplet distribution. Plants exposed to the highest concentration (8 mM) did not survive. The results revealed that in pollen mother cells (PMCs), the relative abnormality rate (RAR) and chromosomal aberration frequency increased with higher herbicide concentrations, peaking at 6 mM. Observed aberrations included clumping, disorientation, laggards, spindle disorientation, micronuclei, chromosomal bridges, and binucleate cells. While clumping, disorientation, and spindle disorientation occurred in all treatments, the percentage of each aberration varied across treatments. Laggards and micronuclei were found in the 2, 4, and 6 mM treatments. Disorientation was the most frequent aberration, followed by clumping and micronuclei, with chromosomal bridges being the least common, followed by binucleate cells. These abnormalities indicate the mutagenic potential of glyphosate. Seedling growth (fresh and dry weight) was adversely affected as glyphosate concentration increased. Additionally, increasing herbicide concentrations led to a significant decrease in photosynthetic pigments, whereas soluble protein content initially increased at lower concentrations and then decreased at 6mM in the leaves of V. mungo . In contrast, proline content increased significantly at higher concentrations (2, 4, and 6 mM). The activities of antioxidant enzymes–catalase, peroxidase, and superoxide dismutase–also consistently increased with higher glyphosate concentrations. The results indicate that glyphosate exposure caused significant genotoxic and physiological disturbances in V. mungo , inducing chromosomal abnormalities, oxidative stress, and dose-dependent increases in antioxidant enzymes, indicating activation of plant defense mechanisms.

There is scant data from India on efficacy and safety of palbociclib and ribociclib in routine clinical practice. This retrospective, observational, single institution study included patients with estrogen and/or progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancers, who received palbociclib or ribociclib with any partner endocrine therapy in any line of treatment between January 2016 and June 2019. Data were analyzed for progression-free survival (PFS), overall survival (OS) and toxicity. The study included 101 female patients with median age of 57 (IQR 48-62) years, of whom 80 (79.2%) were postmenopausal, 79 (78.2%) received palbociclib or ribociclib in second- or later-line treatment, 59 (58.4%) received fulvestrant and 41 (40.6%) received an aromatase inhibitor. In first-line treatment, at a median follow-up of 21.7 (0.5-41.9) months, median PFS and OS were 21.1 (95%CI 16.36-not estimable) months and not reached, respectively. In second- or later-line setting, at a median follow-up of 17.2 (0.5-43.7) months, median PFS and OS were 5.98 (95%CI 4.96-7.89) months and 20.2 (95%CI 14.1-not estimable) months, respectively. Grade 3-4 neutropenia and febrile neutropenia were seen in 45 (45.0%) and 9 (9.0%) patients, respectively while dose reduction was required in 32 (31.7%) patients. In multivariable Cox regression analysis, first-line setting (HR 0.49, 95%CI 0.25-0.97, p = 0.043) and ECOG performance status 1 (HR 0.43, 95%CI 0.20-0.91, p = 0.028) were significantly associated with PFS while only ECOG PS 1 was significantly associated (HR 0.04, 95%CI 0.008-0.206, p = 0.000) with OS. Palbociclib and ribociclib, when used in routine clinical practice in first or subsequent lines of treatment, resulted in efficacy and toxicity outcomes in concordance with those expected from pivotal trials.

ImportanceThe Cancer Aging Research Group (CARG) toxicity score is used to assess toxicity risk in geriatric patients receiving chemotherapy.ObjectiveThe primary aim was to validate the CARG score in geriatric patients treated with curative intent chemotherapy in predicting grade 3–5 toxicities.DesignThis was a longitudinal prospective observational study.SettingTata Memorial Hospital, Mumbai, India, a tertiary cancer care referral centre.ParticipantsPatients, aged ≥65 years, with gastrointestinal, breast or gynaecological stage I–III cancers being planned for curative intent chemotherapy. A total of 270 patients were required for accrual in the study.Exposure(s)Total risk score ranged from 0 (lowest toxicity risk) to 19 (highest toxicity risk).Main outcome(s) and measure(s)The primary endpoint of the study was to evaluate whether the CARG risk score predicted for grade 3–5 toxicities.ResultsThe study cohort of 270 patients had a mean age of 69 (65–83) years, with the most common cancers being gastrointestinal (79%). Fifty-two per cent of patients had atleast one grade 3–5 toxicity. The risk of toxicity was increased with an increasing risk score (42% low risk, 51% medium risk and 79% high risk; p<0.001). There was no association between either Eastern Cooperative Oncology Group (ECOG) performance status (p=0.69) or age-adjusted Charlson Comorbidity Index (p=0.79) risk categories and grade 3–5 chemotherapy toxicities.Conclusions and relevanceThis study validates the CARG risk score in predicting for grade 3–5 toxicities in geriatric oncology patients receiving curative intent chemotherapy and can be considered as the standard of care before planning chemotherapy in every elderly patient.Trial registration numberCTRI/2016/10/007357; Results.