Trastuzumab emtansine induced hyponatremia in breast cancer - A case report.

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), approved for use as an adjuvant treatment for patients with residual disease after neoadjuvant chemotherapy and antihuman epidermal growth factor receptor 2 (HER-2) therapy and in metastatic HER-2-positive breast cancer. Previous studies have shown that T-DM1 has a favorable safety profile, with few high-grade toxicities reported so far. We describe a patient who developed profound hyponatremia-which has not been reported previously-following treatment with adjuvant T-DM1 for HER-2+ breast cancer.

Exposure to Mycophenolic Acid and Its Clinical Response in an Indian Pediatric Population with Nephrotic Syndrome.

Background: Children with nephrotic syndrome experience many side effects and frequent relapses when treated with steroids and other drugs. Mycophenolic acid (MPA) is one of the effective and least toxic drug for the treatment of nephrotic syndrome. This drug needs to be monitored for maximal efficacy and minimal toxicity.

Comparison of imaging modalities for the accurate delineation of arteriovenous malformations (AVM) and evaluation of setup accuracy with reference to non-invasive LINAC-based stereotactic radiosurgery (SRS).

Aims: To compare the accuracy of nidus delineation using magnetic resonance angiography (MRA) to digital subtraction angiography (DSA) and to evaluate setup accuracy of non-invasive frame SRS treatments.

Settings And Design: A prospective observational study of 16 patients who underwent non-invasive frame LINAC-based SRS for brain AVMs.

Materials And Methods: The nidus was separately delineated using DSA and MRA after co-registration onto CT simulation images and compared with respect to their volume and maximum diameters.

COVID-19 Impact on Newly Diagnosed Breast Cancers at Regional Cancer Centre, Thiruvananthapuram-An Audit.

Geethu Babu The coronavirus pandemic has created havoc in every aspect of life including cancer care and was declared a pandemic. This audit was conducted to study the impact of the pandemic on diagnosis and treatment of newly diagnosed breast cancer patients at a tertiary cancer center in South India. A total of 1,647 patients who registered at Regional Cancer Centre (RCC), Thiruvananthapuram, Kerala, India for breast cancer during the period April 1, 2020, to September 30, 2020 (COVID-19 period) as well as April 1, 2019, to September 30, 2019 (pre-COVID-19 period) were included in the study.

Genetic predisposition and high exposure to colistin in the early treatment period as independent risk factors for colistin-induced nephrotoxicity.

Colistin is known to cause nephrotoxicity due to its extensive reabsorption and accumulation in renal tubules. In vitro studies have identified the functional role of colistin transporters such as OCTN2, PEPT2, megalin, and P-glycoprotein. However, the role of these transporter gene variants in colistin-induced nephrotoxicity has not been studied.

Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis: a prospective cohort study.

Objectives: To evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis.

Methods: This prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7-14 days) or long (15-28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement.

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

Background: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear.

Methods: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled.

Efficacy of Crushed Delayed-Release Posaconazole Tablets in Rhino-Orbito-Cerebral Mucormycosis.

A significant proportion of patients with Rhino-orbito-cerebral mucormycosis (ROCM) develop oroantral fistulas. Due to the unclear efficacy of crushed delayed-release posaconazole tablets (DRPT) via nasogastric tube in this group of patients, clinicians often use inferior alternatives like posaconazole suspension. In this prospective study, we report good plasma concentrations (median, 2,639 ng/mL; interquartile range [IQR], 1,690 to 3,575 ng/mL; and range, 1,004 to 4,835ng/mL) and complete cure and survival at 3 and 6 months in 19 such patients.

Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.

Background: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.

Methods: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents.

Effectiveness of triennial screening with clinical breast examination: 14-years follow-up outcomes of randomized clinical trial in Trivandrum, India.

Background: This study presents the preliminary results of a randomized controlled trial (RCT) initiated in January 2006 in India to evaluate the effectiveness of clinical breast examination (CBE) in reducing breast cancer mortality as compared to a no-screening control group reported significant downstaging in the intervention group. The present manuscript reports long-term follow-up outcomes.

Methods: Women 30-69 years old from 133 intervention clusters and 141 control clusters were invited to participate.

Prediction of passing probability and risk evaluation along undivided road under heterogeneous traffic.

This study focuses on the safety part of the passing manoeuvre. Passing is considered as one of the most complex, unavoidable and challenging manoeuvres on two lane roads. A binary logistic regression model was developed to determine the probability of passing or aborting based on field data.

Model-Informed Rationale for Early Therapeutic Drug Monitoring of Colistin in Critically Ill Patients.

Adequate colistin exposure is important for microbiological clearance. This study was performed in critically ill patients >18 years old to develop a simplified nonparametric pharmacokinetic (PK) model of colistin for routine clinical use and to determine the role of dose optimization. The Non-Parametric Adaptive Grid algorithm within the Pmetrics software package for R was used to develop a PK model from 47 patients, and external validation of the final model was performed in 13 patients.

Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations.

Background: In critically ill patients with low albumin, dose individualization of phenytoin is a challenge. The currently used Sheiner-Tozer equation does not accurately predict the free phenytoin concentration in serum and can result in incorrect dose modifications. The best measure to advocate in these patients is the direct-measurement of free phenytoin concentration.

Analytical and clinical validation of dried blood spot and volumetric absorptive microsampling for measurement of tacrolimus and creatinine after renal transplantation.

Background: Serial monitoring of tacrolimus and serum creatinine after renal transplantation is of vital importance. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the estimation of tacrolimus and creatinine, obtained from dried blood spots (DBS) or by volumetric absorptive microsampling (VAMS) was validated and the two sampling strategies were compared with traditional venous sampling.

Methods: The LC-MS/MS assay was validated using a shared extract for the estimation of tacrolimus and creatinine from DBS and VAMS independently.

Educational Status, Cancer Stage, and Survival in South India: A Population-Based Study.

Purpose: Lower socioeconomic status is associated with more advanced cancer at the time of cancer diagnosis. It is unknown whether this leads to inferior survival in low- and middle-income countries. Here, we explore the association between educational level and survival in South India.

Slow parasite clearance, absent K13-propeller gene polymorphisms and adequate artesunate levels among patients with malaria: A pilot study from southern India.

Background: Artemisinin-based combination therapy (ACT) is widely used in India and many generic preparations are available. Delayed response has been reported, suggesting inadequate response to artesunate (AS) or genotypic resistance. We designed a prospective observational study to assess the therapeutic response, elaborate pharmacokinetics of AS and identify Plasmodium falciparum kelch 13 (pfk13) propeller gene polymorphisms among hospitalized Indian patients with severe malaria.

Systemic exposure to 5-fluorouracil and its metabolite, 5,6-dihydrofluorouracil, and development of a limited sampling strategy for therapeutic drug management of 5-fluorouracil in patients with gastrointestinal malignancy.

Aims: 5-Fluorouracil (5-FU) is widely used in combination chemotherapy, and literature suggests pharmacokinetic-guided dosing to improve clinical efficacy and reduce toxicity. This study aimed to determine the pharmacokinetic exposure of both 5-FU and its metabolite, 5,6-dihydrofluorouracil (DHFU), in patients with gastrointestinal malignancy and to establish a simplified strategy to assist in therapeutic drug management for dose optimization.

Methods: This was a prospective, observational study, performed in 27 patients diagnosed with gastrointestinal malignancy who were prescribed 5-FU.

Does addition of postmastectomy radiotherapy improve outcome of patients with pT1-2, N0 triple negative breast cancer as compared to breast conservation therapy?

Background: Triple-negative breast cancers (TNBCs) form a heterogeneous group of cancers typically exhibiting an aggressive behavior resulting in increased risk of locoregional relapse (LRR) and distant metastases. The effect of radiotherapy on LRR risk and overall survival (OS) in women treated with mastectomy alone for early-stage TNBC remains unclear.

Aim: The aim of this study is to compare the locoregional recurrence rate, disease-free survival (DFS), and OS following breast conservation therapy (BCT) or modified radical mastectomy (MRM) alone in women with stage I and IIA TNBC and to assess the impact of tumor and treatment-related factors.

AEBP1 down regulation induced cell death pathway depends on PTEN status of glioma cells.

Glioblastoma (GBM) is the most common aggressive form of brain cancer with overall dismal prognosis (10-12 months) despite all current multimodal treatments. Previously we identified adipocyte enhancer binding protein 1 (AEBP1) as a differentially regulated gene in GBM. On probing the role of AEBP1 over expression in glioblastoma, we found that both cellular proliferation and survival were affected upon AEBP1 silencing in glioma cells, resulting in cell death.

Sociodemographic Factors and Stage of Cancer at Diagnosis: A Population-Based Study in South India.

Purpose: Lower socioeconomic status is associated with inferior cancer survival in high-income countries, but whether this applies to low- and middle-income countries is not well described. Here, we use a population-based cancer registry to explore the association between educational level and stage of cancer at diagnosis in South India.

Methods: We used the Trivandrum District population-based cancer registry to identify all cases of breast and cervical cancer (women) and oral cavity (OC) and lung cancer (men) who were diagnosed from 2012 to 2014.

Advancement to higher communicative functions with transition to iPad app - a case report.

Children with complex communication needs (CCN) develop severe limitation in communication functioning due to restricted access to environment, limited interactions with their communication partners, and few opportunities for communication (Light, 1997). In order to overcome these challenges and to enhance communication abilities, Augmentative Alternative Communication (AAC) can be introduced in intervention. This single case study reports the improvements in communication skills when the child made a transition from a communication book to an iPad speech generating app.

Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy: Second Consensus Report.

Ten years ago, a consensus report on the optimization of tacrolimus was published in this journal. In 2017, the Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicity (IATDMCT) decided to issue an updated consensus report considering the most relevant advances in tacrolimus pharmacokinetics (PK), pharmacogenetics (PG), pharmacodynamics, and immunologic biomarkers, with the aim to provide analytical and drug-exposure recommendations to assist TDM professionals and clinicians to individualize tacrolimus TDM and treatment. The consensus is based on in-depth literature searches regarding each topic that is addressed in this document.

Optimization of dosing regimens of isoniazid and rifampicin in children with tuberculosis in India.

Aims: Pharmacokinetic studies in the past have shown inadequate antituberculosis drug levels in children with the currently available dosing regimens. This study attempted to investigate the pharmacokinetics of isoniazid and rifampicin, when used in children, and to optimize their dosing regimens.

Methods: Data were collected from 41 children, aged 2-16 years, who were being treated with antituberculosis drugs for at least 2 months.