Letrozole for Female Infertility

Letrozole, an aromatase inhibitor that blocks estrogen synthesis by inhibiting the final step of the estrogen biosynthetic pathway, has been used in the applications of a wide range of infertility settings. It has been more than 20 years since the initial clinical trial of letrozole for ovulation induction. In light of the accumulating clinical and basic evidence, the efficacy and safety of letrozole have been identified. This mini review focuses on our current knowledge of the applications and mechanisms of letrozole for female infertility and various questions are put forward about how letrozole could be more effectively used.

Go to the Hospital or Stay Here?: A Randomized Clinical Trial

With the exception of guides for making end of life choices, there are very few if any patient decision aids created for residents of long-term care facilities. Further, only half of patient decision aids produced for any purpose have actually been field tested with patients and even fewer have been evaluated by providers other than the developers of the decision aid. Development of Go to the Hospital or Stay Here? was based on expert experience combined with extensive input from over 270 long-term care residents, their families and their caregivers. The initial clinical trial of this decision aid is reported in this presentation. Increased knowledge, reduced decisional conflict, increased preference for care in the nursing home when possible and a high rating of the helpfulness of the Guide were found in those who received the Guide (n=97) compared to those who did not (n=95).

Immunotherapy for Glioblastoma: Current State, Challenges, and Future Perspectives

Glioblastoma is the most lethal intracranial primary malignancy by no optimal treatment option. Cancer immunotherapy has achieved remarkable survival benefits against various advanced tumors, such as melanoma and non-small-cell lung cancer, thus triggering great interest as a new therapeutic strategy for glioblastoma. Moreover, the central nervous system has been rediscovered recently as a region for active immunosurveillance. There are vibrant investigations for successful glioblastoma immunotherapy despite the fact that initial clinical trial results are somewhat disappointing with unique challenges including T-cell dysfunction in the patients. This review will explore the potential of current immunotherapy modalities for glioblastoma treatment, especially focusing on major immune checkpoint inhibitors and the future strategies with novel targets and combo therapies. Immune-related adverse events and clinical challenges in glioblastoma immunotherapy are also summarized. Glioblastoma provides persistent difficulties for immunotherapy with a complex state of patients’ immune dysfunction and a variety of constraints in drug delivery to the central nervous system. However, rational design of combinational regimens and new focuses on myeloid cells and novel targets to circumvent current limitations hold promise to advent truly viable immunotherapy for glioblastoma.

Mechanistic Inferences from Clinical Reports of SARS-CoV-2

SARS-CoV-2 was identified as the causative pathogen in an outbreak of viral pneumonia cases originating in Wuhan, China, with an ensuing rapid global spread that led it to be declared a pandemic by the WHO on March 11, 2020. Given the threat to public health posed by sequelae of SARS-CoV-2 infection, the literature surrounding patient presentation in severe and non-severe cases, transmission rates and routes, management strategies, and initial clinical trial results have become available at an unprecedented pace. In this review we collate current clinical and immunologic reports, comparing these to reports of previous coronaviruses to identify mechanisms driving progression to severe disease in some patients. In brief, we propose a model wherein dysregulated type I interferon signaling leads to aberrant recruitment and accumulation of innate immune lineages in the lung, impairing establishment of productive adaptive responses, and permitting a pathologic pro-inflammatory state. Finally, we extend these findings to suggest possible treatment options that may merit investigation in randomized clinical trials.

Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound

The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer’s disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions.

Design and virtual implementation of a biomedical registry framework for the enhancement of clinical trials: colorectal cancer example

IntroductionClinical trials generate a large volume of literature and a vast amount of data. Following the 'open science' model, data sharing has enormous potential to strengthen scientific research. Currently, to the best of our knowledge, there is no existing web based Hellenic biomedical registry that displays available patients for clinical trials, providing direct access to registered physicians to all data, assisting them in finding eligible patients in the initial clinical trial recruitment process.MethodsThis paper describes the design and virtual implementation of a web based prototype biomedical registry in Greece. The system represents an eGovernment framework proposal for the central storage of patients' biomedical information and the operations associated with this process. The increasing tendency to include molecular data as prerequisite elements in clinical trials is adopted in the registry philosophy. The designed system is based on free, open source software and it is implemented virtually on a local host environment.ResultsUsing colorectal cancer as an example, valid data from patients increases the reliability index, demonstrating the functionality of the web application.ConclusionIn conclusion, the combination of biomedical data and information technology in order to display potential participants per health unit, facilitates recruitment for clinical trials.

Advances in Noninvasive Glucose Sensing Enabled by Photonics, Acoustics, and Microwaves

More than two decades have passed since the initial clinical trial of noninvasive glucose sensing using optical absorption spectroscopy. Today, noninvasive sensing technologies are expected to meet the increasing demand for high-quality diabetes management. Here, we review the latest advances in noninvasive glucose sensing research, focusing on how photonics-, acoustic- and electronics-based sensing technologies have played key roles in the development of the first noninvasive glucose sensors. We also present our recent work on multiphysics-based glucose sensing using near-infrared photoacoustic spectroscopy and broadband dielectric spectroscopy and a comparison with other competitive technologies.