Skin temperature of the knee was effectively reduced when using a new continuous cold-flow cryocompression device: a randomised controlled crossover trial.

OBJECTIVE: To determine which temperature settings on a new continuous cold-flow cryocompression device effectively reduce knee skin temperature to 10-15 °C, where pain and swelling are expected to be attenuated. DESIGN: Randomised controlled crossover trial. SETTING: University laboratory. PARTICIPANTS: 32 healthy adult participants recruited (1 dropout) with no contraindications to cryocompressive therapy. INTERVENTION: A k-type thermocouple was used to record skin temperature at baseline and every five minutes during a 30-minute cryocompression treatment in a control condition and when using four different device temperature settings (6 °C, 8 °C, 10 °C, and 12 °C) on a continuous cold-flow cryocompression device. Conditions were labelled Control, Con-6, Con-8, Con-10, and Con-12, respectively. MAIN OUTCOME MEASURES: Skin temperature change (°C) throughout cryocompression; time taken (mins) to achieve skin temperature < 15 °C; and the difference between final skin temperature and device temperature setting (°C). RESULTS: Median (IQR) skin temperature after cryocompression was 32.1 °C (29.3-33.4), 12.8 °C (12.1-14.6), 14.3 °C (13.8-15.7), 16.1 °C (15.2-17.3), and 17.7 °C (16.9-18.9) for the Control condition and Con-6, Con-8, Con-10 and Con-12, respectively. It took 20 min (Con-6) and 25 min (Con-8) for skin temperature to reach < 15 °C. A median (IQR) difference of 6.8 °C (6.1-8.6), 6.3 °C (5.8-7.7), 6.1 °C (5.2-7.3), and 5.7 °C (4.9-6.9) for Con-6, Con-8, Con-10, and Con-12, respectively was observed between device temperature setting and final skin temperature. CONCLUSIONS: The device is recommended as it reduced skin temperature to the therapeutic range of 10-15 °C during a 30-minute treatment when using the 6 °C or 8 °C device temperature settings. Future research should determine optimal treatment lengths for cryocompression. CONTRIBUTION OF THE PAPER.

Engineering Controls and Technologies to Enhance Safety in the COVID-19 Pandemic Landscape: Lessons for Laboratories and Non-Laboratories.

Introduction: The global SARS-CoV-2 pandemic ushered in a new way of life in a short time, with many lasting impacts that have yet to be fully realized. This pandemic threat landscape resulted in massive efforts to increase safety, minimize person-to-person transmission, and rethink how society approaches personal and collective health issues. The buildings and environments in which we live, work, and learn now became environments that pose new risks. As a result, many institutions began asking what improvements could be made to those environments to reduce the spread of infection of SARS-CoV-2 and other infectious diseases. Methods: The authors conducted a review of past projects and emerging technologies to evaluate which applications in containment laboratories could represent an example of how engineering controls can improve safety by protecting the workers inside the laboratories as well as the public interfacing the laboratories. Discussion: Engineering controls, technology, and safety systems are hallmarks of modern containment laboratories that may provide some context into extrapolating these elements into non-laboratory environments, providing there is coordination with a risk assessment methodology. In this study, the authors explore new technologies proposed for controlling SARS-CoV-2 in heating, ventilation, and air conditioning systems, and potential impacts to the operations and maintenance of those systems.

Ezatiostat hydrochloride for the treatment of myelodysplastic syndromes.

INTRODUCTION: Myelodysplastic syndromes (MDSs) are associated with significant morbidity due to ineffective hematopoiesis. Given the limited number of drugs approved by the FDA, there is a need for new therapeutic options. Ezatiostat is a novel agent targeting oxidative stress via inhibition of glutathione S-transferase 1. AREAS COVERED: Herein, the authors summarize the standard of care in order to build the framework for therapeutic advancements. The purpose of this paper is to review the body of preclinical and clinical research literature on the investigational agent ezatiostat hydrochloride (TLK199) for the treatment of MDSs. The article includes details of the pathophysiology, pharmacology, toxicity and efficacy of ezatiostat hydrochloride from controlled studies in patients with myelodysplasia. EXPERT OPINION: MDS clonal heterogeneity and clonal architecture complexity has presented a significant technical challenge in developing effective therapies. Ezatiostat offers a unique and specific mechanism to improve the transfusion burden associated with myelodysplasia. Since it is tolerable as a monotherapy, combining ezatiostat with agents such as lenalidomide may have the most potential benefit.

Phase 1b study of safety, tolerability and efficacy of R1507, a monoclonal antibody to IGF-1R in combination with multiple standard oncology regimens in patients with advanced solid malignancies.

BACKGROUND: R1507 is a human IgG1 Mab that binds to the insulin-like growth factor-1 receptor (IGF-1R) and inhibits IGF-1- or IGF-2-mediated anchorage-independent growth of malignant cells. A phase 1b study evaluated the safety, tolerability and efficacy of R1507 in combination with multiple standard oncology regimens. METHODS: R1507 (3, 5, 9, 10 and 16 mg/kg IV, Q2 W or Q3 W) was added to six treatment regimens: gemcitabine + erlotinib (GE); paclitaxel + bevacizumab (PB); carboplatin + etoposide (CE); mFOLFOX6 + bevacizumab (FB); capecitabine + trastuzumab (CT); and sorafenib (S). If tolerable, R1507 dose was escalated utilizing a 3 + 3 + 6 and a 3 + 9 design. RESULTS: A total of 104 patients enrolled into regimens 1-6: 93 % were non-recent diagnoses. Eighteen withdrew for safety [one death, 17 adverse events (AEs)]. A total of 1,337 AEs any grade, across regimens and doses were nausea, vomiting and diarrhea. A total of 123 had grade ≥3 AEs (n = 28 dose level 1; n = 95 dose level 1) and in 60 patients were myelosuppression, fatigue and mucosal inflammation. ORR (PR plus SD) of evaluable patients across six regimens was 36 % with five PRs: regimens PB (non-small cell lung cancer, nasopharyngeal cancer), CE (melanoma), FB (colon cancer) and S (GIST). The GIST pt (>4 prior therapies) had a PR for 3 years. Three patients (breast cancer, melanoma and adenoid cystic carcinoma) were on study for >1 year; 76 % of patients had SD or better for 4 months. CONCLUSIONS: R1507 added to six standard oncology regimens was well tolerated with an ORR of 36 %.

Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation.

BACKGROUND: The contribution of copy-number variation (CNV) to disease has been highlighted with the widespread adoption of array-based comparative genomic hybridisation (aCGH) and microarray technology. Contiguous gene deletions involving ANKRD11 in 16q24.3 are associated with autism spectrum disorder (ASD) and intellectual disability (ID), while 16q24.1 deletions affecting FOXF1 are associated with congenital renal malformations, alveolar capillary dysplasia, and various other abnormalities. The disease associations of deletions in the intervening region, 16q24.2, have only been defined to a limited extent. AIM: To determine whether deletions affecting 16q24.2 are correlated with congenital anomalies. METHODS: 35 individuals, each having a deletion in 16q24.2, were characterised clinically and by aCGH and/or SNP-genotyping microarray. RESULTS: Several of the 35 16q24.2 deletions identified here closely abut or overlap the coding regions of FOXF1 and ANKRD11, two genes that have been previously associated with the disease. 25 patients were reported to have ASD/ID, and three were found to have bilateral hydronephrosis. 14 of the deletions associated with ASD/ID overlap the coding regions of FBXO31 and MAP1LC3B. These same genes and two others, C16orf95 and ZCCHC14, are also included in the area of minimal overlap of the three deletions associated with hydronephrosis. CONCLUSIONS: Our data highlight 16q24.2 as a region of interest for ASD, ID and congenital renal malformations. These conditions are associated, albeit without complete penetrance, with deletions affecting C16orf95, ZCCHC14, MAP1LC3B and FBXO31. The function of each gene in development and disease warrants further investigation.