Initial Safety and Feasibility Results From a Phase 1, Diagnose-and-Treat Trial of Neoadjuvant Intratumoral Cisplatin for Stage IV NSCLC.

Neoadjuvant intratumoral cisplatin has the potential to generate substantial cytotoxicity and immune priming within the tumor environment, while minimizing systemic, off-target, adverse events. We initiated a phase 1A, 3+3 dose-ranging study of neoadjuvant, intratumoral cisplatin, delivered through endobronchial ultrasound bronchoscopy, in the same procedure as the initial diagnosis. There were no dose-limiting toxicity identified at the 20mg level.

Endobronchial ultrasound-guided transbronchial needle injection of cisplatin results in dynamic changes in the tumor immune microenvironment.

Rationale: Direct intratumoral delivery of cisplatin via endobronchial ultrasound guided-transbronchial needle injections (EBUS-TBNI) is a novel approach for salvage treatment of advanced stage non-small cell lung cancer (NSCLC). The goal of this study was to evaluate changes in the tumor immune microenvironment during the course of EBUS-TBNI cisplatin therapy.

Methods: Under an IRB approved protocol, patients with recurrence after radiation therapy who were not receiving other cytotoxic therapy, were prospectively enrolled, and underwent weekly treatments with EBUS-TBNI with additional biopsies obtained for research.

Visualizing intratumoral injections in lung tumors by endobronchial ultrasound.

Real-time endobronchial ultrasound images are crucial for the accurate placement of the needle in peribronchial lung tumors and lymph nodes for diagnostic sampling. Beyond its role as a diagnostic tool, ultrasound-guided bronchoscopy can also aid the delivery of anti-cancer agents intratumorally, enabling diagnosis, staging, and treatment to occur within the same anesthesia, reducing the patient's burden. However, determining drug retention and distribution remains challenging, albeit pivotal in assessing the success or failure of the therapeutic intervention.

Use of Focus Groups to Inform a New Community-Based Youth Diabetes Prevention Program.

There have been few youth-led diabetes prevention programs. Our objective was to conduct focus groups to explore peer influences on adolescent lifestyle behaviors and strategies for implementing a youth peer education model for diabetes prevention. We conducted six focus groups with 52 youth (ages 13-22; 62% male, 38% female; 64% Hispanic, 36% non-Hispanic Black) from East Harlem, NYC.

Boswellic acids, as novel inhibitor targeting peptidoglycan biosynthetic enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) in Escherichia coli.

UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is an essential cytosolic enzyme in the biosynthesis of peptidoglycan. It becomes a potential bacterial target for screening promising antibacterial compounds as it is associated with the early phases of peptidoglycan production. MurA enzyme is conserved and necessary for bacterial viability with no mammalian homolog, which is a well-proven therapeutic research target.

Iron Deficiency Anemia: An Overlooked Complication of Crohn's Disease.

Background: There are few studies to evaluate the association between iron deficiency anemia (IDA) and Crohn's disease (CD). We examined this association in a USA-based cohort of patients with CD.

Methods: We queried the Nationwide Readmission Databases 2018 using the International Classification of Disease, 10th Revision, and Clinical Modification (ICD-10-CM) codes to identify all adult patients admitted with a diagnosis of CD.

Burden and Predictors of Non-Alcoholic Fatty Liver Disease in a Retrospective Cohort of Patients With Crohn's Disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is an emerging extraintestinal manifestation (EIM) of Crohn's disease (CD). We aimed to investigate the prevalence and comorbid predictors of NAFLD in patients with CD.

Methods: We conducted a nationwide retrospective cohort study to determine the prevalence, characteristics, comorbidities, and hospitalization outcomes associated with NAFLD in patients with CD.

Identification of novel MurA inhibitors using approach, their validation and elucidation of mode of inhibition.

UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is an important enzyme involved in the first cytosolic step of bacterial cell wall synthesis. In this study a combination of ligand based and structure based virtual screening methods were utilised for screening of more than 50,000 drug-like compounds from CSIR-IIIM in-house compound library in order to identify potent inhibitors of MurA. The identified hits were validated in vitro under various incubation conditions using Malachite green phosphate assay, and two potent hits viz 3772-9534 and D396-0012 were identified.

Cancer Care in the Wake of a Cyberattack: How to Prepare and What to Expect.

Purpose: Cyberattacks targeting health care organizations are becoming more frequent and affect all aspects of care delivery. Cancer care is particularly susceptible to major disruptions because of the potential of immediate and long-term consequences for patients who often rely on timely diagnostic testing and regular administration of systemic therapy in addition to other local treatment modalities to cure or control their diseases. On October 28, 2020, a cyberattack was launched on the University of Vermont Health Network with wide-ranging consequences for oncology, including loss of access to all network intranet servers, e-mail communications, and the electronic medical record (EMR).

Screening of compound library identifies novel inhibitors against the MurA enzyme of Escherichia coli.

Bacterial cell has always been an attractive target for anti-infective drug discovery. MurA (UDP-N-acetylglucosamine enolpyruvyl transferase) enzyme of Escherichia coli (E.coli) is crucial for peptidoglycan biosynthetic pathway, as it is involved in the early stages of bacterial cell wall biosynthesis.

Detection of the in vitro modulation of Plasmodium falciparum Arf1 by Sec7 and ArfGAP domains using a colorimetric plate-based assay.

The regulation of human Arf1 GTPase activity by ArfGEFs that stimulate GDP/GTP exchange and ArfGAPs that mediate GTP hydrolysis has attracted attention for the discovery of Arf1 inhibitors as potential anti-cancer agents. The malaria parasite Plasmodium falciparum encodes a Sec7 domain-containing protein - presumably an ArfGEF - and two putative ArfGAPs, as well as an Arf1 homologue (PfArf1) that is essential for blood-stage parasite viability. However, ArfGEF and ArfGAP-mediated activation/deactivation of PfArf1 has not been demonstrated.

Progress Toward Polio Eradication - Worldwide, January 2016-March 2018.

In 1988, when an estimated 350,000 cases of poliomyelitis occurred in 125 countries, the World Health Assembly resolved to eradicate polio globally. Transmission of wild poliovirus (WPV) continues uninterrupted in only three countries (Afghanistan, Nigeria, and Pakistan) (1), and among the three serotypes, WPV type 1 (WPV1) remains the only confirmed circulating type. This report describes global progress toward polio eradication during January 2016-March 2018, and updates previous reports (2).

Strengthening value-based medication management in a free clinic for the uninsured: Quality interventions aimed at reducing costs and enhancing adherence.

Skyrocketing costs of prescription medications in the USA pose a significant threat to the financial viability of safety net clinics that opt to supply medications at low to no out-of-pocket costs to patients. At the East Harlem Health Outreach Partnership clinic of the Icahn School of Medicine at Mount Sinai, a physician-directed student-run comprehensive primary care clinic for uninsured adults of East Harlem, expenditures on pharmaceuticals represent nearly two-thirds of annual costs. The practice of minimising costs while maintaining quality, referred to as care, represents a critical cost-saving opportunity for safety net clinics as well as for more economical healthcare in general.

Small-cell transformation of -rearranged non-small-cell adenocarcinoma of the lung.

Anaplastic lymphoma kinase (ALK) gene rearrangements are present in ∼5% of non-small-cell lung cancers (NSCLCs). These rearrangements occur because of a chromosomal inversion within the short arm of Chromosome 2, which results in the formation of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion oncogene. Whereas NSCLC transformation to SCLC is a rare phenomenon described in epidermal growth factor receptor (EGFR) mutant cancers primarily after treatment with targeted therapy, it is exceedingly rare in ALK-rearranged adenocarcinomas.

Assessment of an Innovative Voluntary Substance Abuse Treatment Program Designed to Replace Compulsory Drug Detention Centers in Malaysia.

Background: As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services.

Objectives: We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan.

Methods: In June-July 2012, a cross-sectional convenience survey of 96 C&C inpatients and outpatients who entered treatment >30 days previously was conducted to assess drug use, criminal justice experience, medical co-morbidities, motivation for seeking treatment, and attitudes towards the C&C.

Genetic diversity of Glossina fuscipes fuscipes along the shores of Lake Victoria in Tanzania and Kenya: implications for management.

Background: Tsetse flies (Diptera: Glossinidae) are sole vectors for trypanosomiasis, which affect human health and livestock productivity in Africa. Little is known about the genetic diversity of Glossina fuscipes fuscipes, which is an important species in Tanzania and Kenya. The main objective of the study was to provide baseline data to determine the genetic variability and divergence of G.

Access to Care in Vermont: Factors Linked With Time to Chemotherapy for Women With Breast Cancer-A Retrospective Cohort Study.

Purpose: In the rural United States, there are multiple potential barriers to the timely initiation of chemotherapy. The goal of this study was to identify factors associated with delays in the time from initial diagnosis to first systemic therapy (TTC) among women with breast cancer in Vermont.

Methods: Using data from the Vermont Cancer Registry, we explored TTC for 702 female Vermont residents diagnosed with stage I to III breast cancer between 2006 and 2010 who received adjuvant chemotherapy.

Double trouble: para-neoplastic anti-PCA-2 and CRMP-5-mediated small fibre neuropathy followed by chorea associated with small cell lung cancer and evolving radiological features.

Patients with Purkinje cell cytoplasmic autoantibody type 2 (PCA-2) and collapsin response-mediator protein-5 (CRMP-5) autoantibody can present with multifocal elements of encephalomyeloneuropathy. Except for an anecdotal report, case descriptions of paraneoplastic small fibre neuropathy are lacking. We report paraneoplastic small fibre neuropathy followed by chorea associated with small cell lung cancer.

Pretreatment drug use characteristics and experiences among patients in a voluntary substance abuse treatment center in Malaysia: A mixed-methods approach.

Background: Drug use in Malaysia remains a significant public health and social problem despite implementation of harsh punitive drug policies such as forcibly placing suspected drug users into compulsory drug detention centers (CDDCs). Following criticism over human right violations in CDDCs, Malaysia has begun to transition towards voluntary drug treatment centers known as Cure & Care (C&C) centers. To best serve the needs of regional C&C centers, data on drug use are essential among patients accessing treatment.

Discovery of new proteasome inhibitors using a knowledge-based computational screening approach.

Mycobacterium tuberculosis bacteria cause deadly infections in patients [Corrected]. The rise of multidrug resistance associated with tuberculosis further makes the situation worse in treating the disease. M.

An exploratory qualitative assessment of self-reported treatment outcomes and satisfaction among patients accessing an innovative voluntary drug treatment centre in Malaysia.

Background: In Malaysia, compulsory drug detention centres (CDDCs) hold suspected drug users for two years without adjudication. Acute detoxification without healthcare access has been documented. CDDCs are criticized globally due to ineffectiveness in treating addiction and human rights violations.

Endobronchial ultrasound-guided transbronchial needle injection for local control of recurrent non-small cell lung cancer.

Rationale: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an established technique for the diagnosis of thoracic malignancies. Non-ultrasound-guided transbronchial needle injection has been used previously to deliver chemotherapeutic agents.

Objectives: To use endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) to achieve local control of recurrent early-stage lung cancer.