Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study.

Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL.

Complete Response to tenalisib and romidepsin with long-term maintenance using tenalisib monotherapy in a patient with relapsed and refractory sézary syndrome.

Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common subtypes of cutaneous T cell lymphomas (CTCL). Advanced-stage MF/SS have poor prognoses and may be refractory to multiple systemic treatments. These cases can be difficult to achieve and maintain complete response and there is a need for novel therapeutics.

The panorama of pulmonary leiomyoma: A tale of two tumours.

Pulmonary leiomyoma has a diverse clinical spectrum of disease. Here we describe two patients with vastly different presentations. The first case is a 23-year-old female with a chronic cough and no visible tracheal lesion on computer tomography (CT) chest imaging.

A first in man study to evaluate the safety, pharmacokinetics and pharmacodynamics of RP7214, a dihydroorotate dehydrogenase inhibitor in healthy subjects.

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that is essential for pyrimidine de novo synthesis. Rapidly growing cancer cells and replicating viruses are dependent on host cell nucleotides, the precursors of which are provided by DHODH. Hence, DHODH becomes an ideal target for pharmacological intervention.

A first-in-human study to evaluate the safety, tolerability and pharmacokinetics of RP3128, an oral calcium release-activated calcium (CRAC) channel modulator in healthy volunteers.

What Is Known And Objective: RP3128, a novel, orally available modulator of calcium released activated calcium (CRAC) channel, is being developed for the potential treatment of autoimmune and inflammatory diseases. RP3128 showed nano-molar potency and activity in a range of in vitro and in vivo models of inflammation. We report a first-in-human study investigating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RP3128 in healthy subjects.

Phase I/Ib Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma.

Tenalisib (RP6530), a dual phosphoinositide 3-kinase δ/γ inhibitor was evaluated in a phase I/Ib study for maximum tolerated dose (MTD), pharmacokinetics, and efficacy in patients with relapsed/refractory peripheral and cutaneous T-Cell Lymphoma (TCL). Histologically confirmed (TCL) patients, with ≥1 prior therapy received Tenalisib orally in a 28-day cycle in doses of 200 to 800 mg twice daily (800 mg in fasting and fed state) in escalation phase ( = 19) and 800 mg twice daily (fasting) in expansion phase ( = 39). The most frequently reported treatment emergent adverse events (TEAE) and related TEAE were fatigue (45%) and transaminase elevations (33%), respectively.

A First-in-human Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor, in Patients With Relapsed/Refractory Hematologic Malignancies: Results From the European Study.

Background: Tenalisib (RP6530) is a novel, highly specific, dual phosphoinositide-3 kinases (PI3K) δ/γ inhibitor with nano-molar potency.

Material And Methods: This was a phase I, open-label, 3 + 3 dose escalation, maximum tolerated dose determination study to evaluate the safety, pharmacokinetics, and efficacy of tenalisib in patients with relapsed/refractory hematologic malignancies. Tenalisib was administered orally twice/thrice daily in 28-day cycles with starting dose of 25 mg twice daily.

Review of HIV testing recommendations in Australian specialty guidelines for HIV indicator conditions: a missed opportunity for recommending testing?

Background: Australian National human immunodeficiency virus (HIV) Testing policy recommends HIV indicator condition-based testing, adapted from the European AIDS Clinical Society (EACS) guidelines.

Aim: To evaluate the extent that Australian non-HIV specialty guidelines mention and recommend HIV testing in HIV indicator conditions.

Methods: EACS guidelines were reviewed to produce a list of 24 AIDS-defining conditions (ADC) and 31 indicator conditions (IC) where HIV prevalence >0.

Diagnostic Yield of Timing Blood Culture Collection Relative to Fever.

Background: Conventional practice involves obtaining a blood culture during or immediately after a fever to increase diagnostic yield. There are no data to support this practice in children.

Methods: Retrospective single-center case-control study of children (0-18 years) who had blood cultures performed as part of routine care.

Critical sources of bacterial contamination and adoption of standard sanitary protocol during semen collection and processing in Semen Station.

Aim: The present investigation was conducted to locate the critical sources of bacterial contamination and to evaluate the standard sanitation protocol so as to improve the hygienic conditions during collection, evaluation, and processing of bull semen in the Semen Station.

Materials And Methods: The study compared two different hygienic procedures during the collection, evaluation and processing of semen in Central Semen Station, Anjora, Durg. Routinely used materials including artificial vagina (AV) inner liner, cone, semen collection tube, buffer, extender/diluter, straws; and the laboratory environment like processing lab, pass box and laminar air flow (LAF) cabinet of extender preparation lab, processing lab, sealing filling machine, and bacteriological lab were subjected to bacteriological examination in two phases of study using two different sanitary protocols.

Effect of species, breed, and age on bacterial load in bovine and bubaline semen.

Aim: The present study was conducted to investigate the effect of species, breed and age on bacterial load in fresh and frozen semen of Cattle and Buffalo bull.

Materials And Methods: Present study covered 56 cow and 10 buffalo bulls stationed at Central Semen Station Anjora, Durg (Chhattisgarh). Impact of breeds on bacterial load in semen was assessed using six breeds of cattle viz.

ACR appropriateness criteria radiologic management of infected fluid collections.

The best management of infected fluid collections depends on a careful assessment of clinical and anatomic factors as well as an up-to-date review of the published literature, to be able to select from a host of multidisciplinary treatment options. This article reviews conservative, radiologic, endoscopic, and surgical options and their best application to infected fluid collections as determined by the ACR Appropriateness Criteria Expert Panel on Interventional Radiology. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel.

ACR Appropriateness Criteria radiologic management of benign and malignant biliary obstruction.

The optimal treatment for patients with biliary obstruction varies depending on the underlying cause of the obstruction, the clinical condition of the patient, and anticipated long-term effects of the procedure performed. Endoscopic and image-guided procedures are usually the initial procedures performed for biliary obstructions. Various options are available for both the radiologist and endoscopist, and each should be considered for any individual patient with biliary obstruction.

ACR Appropriateness Criteria radiologic management of hepatic malignancy.

Management of hepatic malignancy is a challenging clinical problem involving several different medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and locoregional therapies, such as thermal ablation and transarterial embolization.

Nontarget embolization complicating transarterial chemoembolization in a patient with hepatocellular carcinoma.

Nontarget embolization during transarterial chemoembolization, although infrequent, can be a serious complication. The authors describe a case of nontarget gastric embolization to the stomach after transarterial chemoembolization and describe the published incidence of nontarget embolization to various organs, its diagnosis, treatment, and possible outcomes.

Hepatic abscess complicating transarterial chemoembolization in a patient with liver metastases.

Hepatic abscess following transarterial chemoembolization is an uncommon complication. The authors describe a case of liver abscess after transarterial chemoembolization for neuroendocrine liver metastases, including risk factors, prophylaxis, treatment, and outcomes.

ACR appropriateness criteria® radiologic management of thoracic nodules and masses.

Pulmonary and mediastinal masses represent a wide range of pathologic processes with very different treatment options. Although advances in imaging (such as PET and high-resolution CT) help in many cases with the differential diagnosis of thoracic pathology, tissue samples are frequently needed to determine the best management for patients presenting with thoracic masses. There are many options for obtaining tissue samples, each of which has its own set of benefits and drawbacks.

Exploring the use of soft X-ray microscopy for imaging subcellular structures of the inner ear.

The soft X-ray microscope at the Lawrence Berkeley National Laboratory was developed for visualization of biological tissue. Soft X-ray microscopy provides high-resolution visualization of hydrated, non-embedded and non-sectioned cells and is thus potentially an alternative to transmission electron microscopy. Here we show for the first time soft X-ray micrographs of structures isolated from the guinea-pig inner ear.

Experimental third ventriculostomy performed using endovascular surgical techniques and their adaptation to percutaneous intradural neuronavigation: proof of concept cadaver study.

Objective: Endoscopic third ventriculostomy has developed into a therapeutic alternative to shunting for the management of carefully selected patients with primarily noncommunicating hydrocephalus. This procedure, however, requires a general anesthetic and necessitates violation of the brain parenchyma and manipulation near vital neural structures to access the floor of the third ventricle. Using two cadavers and off-the-shelf angiographic catheters, we sought to determine whether it was possible to navigate a catheter, angioplasty balloon, and stent percutaneously through the subarachnoid space from the thecal sac into the third ventricle so as to perform a third ventriculostomy from below.