Clinical Outcomes of Neoadjuvant Therapy Versus Upfront Surgery in Resectable Pancreatic Cancer: Systematic Review and Meta-analysis of Latest Randomized Controlled Trials.

Background: Survival and surgical benefits of neoadjuvant treatments (NAT) in resectable pancreatic cancer (RPC) remains unclear. The role of NAT in providing additional benefits to reduce biological aggressiveness and recurrence is worth elucidating. We assessed the latest randomized controlled trials (RCTs).

Testosterone Replacement Therapy and Risk of COVID-19 and Effect of COVID-19 on Testosterone's Treatment Effect.

Context: Whether circulating testosterone, dihydrotestosterone, and estradiol levels or testosterone replacement therapy (TRT) affects the risk of COVID-19 and whether COVID-19 affects response to TRT remains unknown.

Objective: The study evaluated whether baseline testosterone, dihydrotestosterone, and estradiol levels or TRT are associated with risk of developing COVID-19 and whether COVID-19 affects treatment response to TRT.

Methods: Among 5204 men, aged 45 to 80 years, with hypogonadism in the TRAVERSE trial, 379 developed COVID-19.

Ambulatory Blood Pressure Parameters Among Men With Hypogonadism Treated With Testosterone Transdermal Therapy.

Objective: Studies are needed to examine the effects of testosterone replacement therapy on ambulatory blood pressure (BP) parameters. This study assessed a testosterone transdermal system (TTS) using 24-hour ambulatory BP monitoring.

Methods: In a single-arm, noninferiority trial conducted at 41 US sites, 168 men (mean age: 56.

Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism: A Randomized Clinical Trial.

Importance: Testosterone deficiency causes mild anemia. Whether testosterone replacement therapy (TRT) can correct anemia or prevent the development of anemia in men with hypogonadism remains incompletely understood.

Objective: To assess the efficacy of TRT in correcting anemia in men with hypogonadism and anemia, and reducing the risk of developing anemia in those without anemia.

Cardiovascular Safety of Testosterone-Replacement Therapy.

Background: The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined.

Methods: In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.

Low-Density Lipoprotein Cholesterol and Risk of Recurrent Vascular Events in Chinese Patients With Ischemic Stroke With and Without Significant Atherosclerosis.

Background Recent trials have shown that low-density lipoprotein cholesterol (LDL-C) <1.80 mmol/L (<70 mg/dL) is associated with a reduced risk of major adverse cardiovascular events in White patients with ischemic stroke with atherosclerosis. However, it remains uncertain whether the findings can be generalized to Asian patients, or that similar LDL-C targets should be adopted in patients with stroke without significant atherosclerosis.

Nfkb2 variants reveal a p100-degradation threshold that defines autoimmune susceptibility.

NF-κB2/p100 (p100) is an inhibitor of κB (IκB) protein that is partially degraded to produce the NF-κB2/p52 (p52) transcription factor. Heterozygous NFKB2 mutations cause a human syndrome of immunodeficiency and autoimmunity, but whether autoimmunity arises from insufficiency of p52 or IκB function of mutated p100 is unclear. Here, we studied mice bearing mutations in the p100 degron, a domain that harbors most of the clinically recognized mutations and is required for signal-dependent p100 degradation.

Delays in Stroke Onset to Hospital Arrival Time During COVID-19.

Background And Purpose: The current coronavirus disease 2019 (COVID-19) pandemic represents a global public health crisis, disrupting emergency healthcare services. We determined whether COVID-19 has resulted in delays in stroke presentation and affected the delivery of acute stroke services in a comprehensive stroke center in Hong Kong.

Methods: We retrospectively reviewed all patients with transient ischemic attack and stroke admitted via the acute stroke pathway of Queen Mary Hospital, Hong Kong, during the first 60 days since the first diagnosed COVID-19 case in Hong Kong (COVID-19: January 23, 2020-March 24, 2020).

Deletion of self-reactive CCR7- thymocytes in the absence of MHC expression on thymic epithelial cells.

The selection of αβ T cells in the thymus is punctuated by checkpoints at which thymocytes differentiate or undergo apoptosis. Wave 1 deletion is defined as apoptosis within nascent αβ T-cell antigen receptor (TCR)-signalled thymocytes that lack CCR7 expression. The antigen-presenting cell (APC) types that mediate wave 1 deletion are unclear.

Device Sizing Guided by Echocardiography-Based Three-Dimensional Printing Is Associated with Superior Outcome after Percutaneous Left Atrial Appendage Occlusion.

Background: Left atrial appendage (LAA) occlusion is an alternative to anticoagulation for stroke prevention in patients with atrial fibrillation. Accurate device sizing is crucial for optimal outcome. Patient-specific LAA models can be created using three-dimensional (3D) printing from 3D transesophageal echocardiographic (TEE) images, allowing in vitro model testing for device selection.

Comparison of three left atrial appendage occlusion devices for stroke prevention in patients with non-valvular atrial fibrillation: a single-centre seven-year experience with WATCHMAN, AMPLATZER Cardiac Plug/Amulet, LAmbre: Comparison of three LAAO devices for stroke prevention.

Aims: We aimed to compare long-term "real-world" outcomes of three left atrial appendage occlusion (LAAO) devices for stroke prevention in a Chinese population with non-valvular atrial fibrillation (NVAF).

Methods And Results: Consecutive patients who underwent LAAO from June 2009 to October 2016 at a university-affiliated hospital were retrospectively analysed. In-hospital and major adverse events (MAE) including mortality, stroke and major bleeding rates were compared by LAAO device.

Occlusion of a Multilobed Shallow Left Atrial Appendage Using a Special LAmbre Device After Failed Watchman Implantation.

Although reported failure rates of the Watchman device are low, the ballshaped device is not suitable for shallow and multilobed left atrial appendages (LAAs). The LAmbre device is available in two configurations - standard (cover 4-6 mm larger in diameter than the umbrella) and special (cover 12- 14 mm larger than the umbrella) - which allows the closure of a wide range of LAA anatomies. This case illustrates that the LAmbre device can be used for complex LAA anatomies that are not suitable for the Watchman device.

Ulipristal Acetate for Treatment of Uterine Leiomyomas: A Randomized Controlled Trial.

Objective: To assess the efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas.

Methods: This phase 3, double-blind, double-dummy, placebo-controlled trial randomized premenopausal women (18-50 years) with uterine leiomyomas and abnormal uterine bleeding to once-daily 5 mg ulipristal, 10 mg ulipristal, or placebo in two 12-week treatment courses separated by a drug-free interval of two menses. Coprimary end points were rates of and time to amenorrhea during course 1.

αβ T-cell receptors with a central CDR3 cysteine are enriched in CD8αα intraepithelial lymphocytes and their thymic precursors.

The thymus plays a crucial role in immune tolerance by exposing developing T cells (thymocytes) to a myriad of self-antigens. Strong T-cell receptor (TCR) engagement induces tolerance in self-reactive thymocytes by stimulating apoptosis or selection into specialized T-cell lineages, including intestinal TCRαβ CD8αα intraepithelial lymphocytes (IEL). TCR-intrinsic amino acid motifs that can be used to predict whether a TCR will be strongly self-reactive remain elusive.

Ulipristal Acetate for Treatment of Symptomatic Uterine Leiomyomas: A Randomized Controlled Trial.

Objective: To assess efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas.

Methods: This phase 3, double-blind, placebo-controlled study enrolled premenopausal women (aged 18-50 years) with abnormal uterine bleeding, one or more discrete leiomyomas, and uterine size 20 weeks of gestation or less. Patients were randomized 1:1:1 to 5 mg ulipristal, 10 mg ulipristal, or placebo once daily for 12 weeks followed by 12-week drug-free follow-up.

Indirect presentation in the thymus limits naive and regulatory T-cell differentiation by promoting deletion of self-reactive thymocytes.

Acquisition of T-cell central tolerance involves distinct pathways of self-antigen presentation to thymocytes. One pathway termed indirect presentation requires a self-antigen transfer step from thymic epithelial cells (TECs) to bone marrow-derived cells before the self-antigen is presented to thymocytes. The role of indirect presentation in central tolerance is context-dependent, potentially due to variation in self-antigen expression, processing and presentation in the thymus.

Manufacturing Process Changes and Reduced Skin Irritations of an Adhesive Patch Used for Continuous Glucose Monitoring Devices.

Adhesives used for continuous glucose monitoring (CGM) devices can cause skin irritations, which sometimes lead to abandonment of the therapy. A previous sensor manufacturing process involved two separate adhesives-one applied to the skin-facing surface of the fabric patch, and a second, ethyl cyanoacrylate-based adhesive, which secured the plastic transmitter housing to the superficial side of the patch. Our current process for attaching the transmitter housing to the fabric patch uses heatstaking, wherein the housing is heated and pressed against the patch with a specialized assembly apparatus.