Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

Frailty assessment: An emerging concept in aged People Living with HIV (PLHIV).

Introduction: As the life expectancy of People Living with HIV (PLHIV) has improved with effective antiretroviral treatment (ART), they now face the challenges of accelerated ageing. Frailty is an emerging concept in the management of PLHIV and up to 28% of PLHIV are identified as frail. Frailty is a determinant of adverse clinical outcomes and is a complex clinical endpoint that has not been studied in India. This exploratory study was done to evaluate frailty and its determinants among PLHIV in India. Materials and Methods: This was a cross-sectional study in 76 PLHIV aged 50 years or more. All the study subjects underwent a comprehensive clinical assessment. The Fried's criteria and Veterans Aging Cohort Study (VACS) Index were used to evaluate for frailty. Socio-demographic, clinical, immunological, and virological variables were assessed for their association with frailty. The study was registered under Clinical Trials Registry-India (ICMR-NIMS): REF/2019/05/025616. Results: The mean age of the subjects was 56.05 ± 5.8 years (range 50-76), and males constituted 81.57% (62/76) of the subjects and majority (60.53%) were underweight. On frailty assessment, 57.89% of the PLHIV were identified as prefrail/frail. Frailty had a significant association with low CD4 count (P = 0.0001) and number of comorbidities (P = 0.017) especially when comorbidities ≥2 (P = 0.04) and polypharmacy (P = 0.033). VACS index, polypharmacy, and low CD4 count ≤200 cells/mm3 were strong predictors of frailty. On multivariate regression analysis, CD4 count ≤200 emerged as the strongest independent predictor of frailty. Conclusion: The study highlighted the high prevalence of frailty and under nutrition among aged PLHIV. The study emphasizes the need for a shift away from traditional clinical endpoints to other outcome measures for a holistic approach to PLHIV.

Pneumocystis jirovecii infection of bilateral adrenal glands in an immunocompetent adult: a case report.

Pneumocystis jirovecii (PJ) infection is one of the most common opportunistic infections occurring in patients with HIV/AIDS and other immunocompromised states. It is not known to cause clinically significant illness in immunocompetent hosts. We report a 48-year-old HIV-negative, diabetic male who presented with fever and adrenal insufficiency. Abdominal sonography and PET-CT revealed bilateral enlarged adrenal glands with peripheral enhancement and central necrosis. An endoscopic ultrasound-guided fine-needle aspiration cytology of the left adrenal gland demonstrated well-defined, round cysts of PJ. There was no evidence of pulmonary involvement. The response to first-line treatment was poor and the patient responded to second-line treatment for Pneumocystis infection.

Pheochromocytoma and tetralogy of Fallot: Coincidence or a rare association?

We report the case of a 25-year-old woman with tetralogy of Fallot who presented with chest pain and hypertension, and on further investigation, was diagnosed with a pheochromocytoma in the right adrenal gland. She underwent surgical excision of the tumor. While the simultaneous occurrence of these two diseases is extremely rare, the suspicion of a possible relationship has been raised in the past.