Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patients.

Use of natural user interfaces for image navigation during laparoscopic surgery: initial experience.

BACKGROUND: Surgical environments require special aseptic conditions for direct interaction with the preoperative images. We aim to test the feasibility of using a set of gesture control sensors combined with voice control to interact in a sterile manner with preoperative information and an integrated operating room (OR) during laparoscopic surgery. MATERIAL AND METHODS: Two hepatectomies and two partial nephrectomies were performed by three experienced surgeons in a porcine model. The Kinect, Leap Motion, and MYO armband in combination with voice control were used as natural user interfaces (NUIs). After surgery, surgeons completed a questionnaire about their experience. RESULTS: Surgeons required <10 min training with each NUI. They stated that NUIs improved the access to preoperative patient information and kept them more focused on the surgical site. The Kinect system was reported as the most physically demanding NUI and the MYO armband in combination with voice commands as the most intuitive and accurate. The need to release one of the laparoscopic instruments in order to use the NUIs was identified as the main limitation. CONCLUSIONS: The presented NUIs are feasible to directly interact in a more intuitive and sterile manner with the preoperative images and the integrated OR functionalities during laparoscopic surgery.

Spanish Registry of Acute Aortic Syndrome (RESA). Changes in therapeutic management and lower mortality in acute aortic syndrome.

INTRODUCTION AND OBJECTIVES: The Spanish Registry of Acute Aortic Syndrome (RESA) was launched in 2005 to identify the characteristics of acute aortic syndrome (AAS) in Spain. The aim of this study was to analyze the differences in management and mortality in the 3 RESA iterations. METHODS: We analyzed data from patients with AAS prospectively included by 24 to 30 tertiary centers during the 3 iterations of the registry: RESA I (2005-2006), RESA-II (2012-2013), and RESA III (2018-2019). RESULTS: AAS was diagnosed in 1902 patients (74% men; age, 60.7±12.5 years): 1329 (69.9%) type A and 573 (30.1%) type B. Comparison of the 3 periods revealed that the use of computed tomography increased as the first diagnostic technique (77.1%, 77.9%, and 84.2%, respectively; P=.001). In type A, surgical management increased (79.6%, 78.7%, and 84.5%; P=.045) and overall mortality decreased (41.2%, 34.5%, and 31.2%; P=.002), due to a reduction in surgical mortality (33.4%, 25.1%, and 23.9%; P=.003). In type B, endovascular treatment increased (22.8%, 32.8%, and 38.7%; P=.006), while medical and surgical treatment decreased. Overall type B mortality also decreased (21.6%, 16.1%, and 12.0%; P=.005) in line with a reduction in mortality with medical (16.8%, 13.8%, and 8.8%, P=.030) and endovascular (27.0%, 18.0%, and 9.2%; P=.009) treatments. CONCLUSIONS: The iterations of RESA show a decrease in mortality from type A AAS, coinciding with an increase in surgical treatment and a reduction in surgical mortality. In type B, the use of endovascular treatment was associated with improved survival, allowing better management in patients with complications.

Impact of Preoperative Pulmonary Hypertension on Survival in Patients Undergoing Elective Heart Transplant.

BACKGROUND: Pulmonary arterial hypertension (PAH) represents a marker of bad prognosis in left heart disease. Nonetheless, the effect on survival after heart transplant remains controversial. The objective was to study the impact of preoperative PAH on survival in patients undergoing elective heart transplant. METHODS: A retrospective study of 173 transplant recipients was conducted at a single hospital from January 2009 to December 2018. Congenital etiology and emergent heart transplant were exclusion criteria as well as those patients without enough data in the hemodynamic study. Two groups were considered: A (without PAH) and B (with HTP). PAH was classified as mild (mean pulmonary arterial pressure [mPAP] 25-34 mm Hg, pulmonary vascular resistance [PVR] 2.5-3.4 Wood units and/or transpulmonary gradient [TPG] 13-16 mm Hg), moderate (mPAP 35-44 mm Hg, PVR 3.5-4.9 Wood units and/or TPG 17-19 mm Hg), and severe (mPAP > 44 mm Hg, PVR > 4.9 Wood units and/or TPG > 19 mm Hg). RESULTS: A total of 102 patients were enrolled; 71.6% were male and average age was 52.3 (SD, 10.02) years. The main etiology was ischemic cardiomyopathy; 13.7% underwent previous heart operations. A total of 61 patients (59.8%) had PAH prior to heart transplant: 25 mild, 34 moderate, and 2 severe. Mean overall survival after transplant was 79.9 (SD, 5.68) months, without differences between the 2 groups (P = .82). One-month survival was 89% (the main cause of mortality was primary graft dysfunction), and 1-year survival was 78%. Four patients required mechanical circulatory support during early post-transplant period. CONCLUSIONS: Preoperative PAH does not have a significant impact on survival in elective heart transplant.

Successful application of large microneedle patches by human volunteers.

We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600µm), were prepared from aqueous blends of 15% w/w Gantrez® S97 and 7.5% w/w poly(ethyleneglycol) 10,000Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500µm. Ten human volunteers successfully self-inserted the microneedles of these larger patches in their skin, following appropriate instruction, as confirmed by transepidermal water loss measurements. The mean insertion depth ranged between 300 and 450µm over the area of the large patches. That this was not significantly different to a single unit MN patch self-applied by the same volunteers is encouraging. Microneedle patch sizes much larger than the 1-2cm2 will be required if this technology is to be successfully translated to clinic for delivery of drug substances. The work described here suggests that use of such larger patches by patients can be successful, potentially opening up the possibility for a significant expansion of the size of the market for transdermal drug delivery.

Hydrogel-Forming Microneedle Arrays Allow Detection of Drugs and Glucose In Vivo: Potential for Use in Diagnosis and Therapeutic Drug Monitoring.

We describe, for the first time the use of hydrogel-forming microneedle (MN) arrays for minimally-invasive extraction and quantification of drug substances and glucose from skin in vitro and in vivo. MN prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) (11.1% w/w) and poly(ethyleneglycol) 10,000 daltons (5.6% w/w) and crosslinked by esterification swelled upon skin insertion by uptake of fluid. Post-removal, theophylline and caffeine were extracted from MN and determined using HPLC, with glucose quantified using a proprietary kit. In vitro studies using excised neonatal porcine skin bathed on the underside by physiologically-relevant analyte concentrations showed rapid (5 min) analyte uptake. For example, mean concentrations of 0.16 µg/mL and 0.85 µg/mL, respectively, were detected for the lowest (5 µg/mL) and highest (35 µg/mL) Franz cell concentrations of theophylline after 5 min insertion. A mean concentration of 0.10 µg/mL was obtained by extraction of MN inserted for 5 min into skin bathed with 5 µg/mL caffeine, while the mean concentration obtained by extraction of MN inserted into skin bathed with 15 µg/mL caffeine was 0.33 µg/mL. The mean detected glucose concentration after 5 min insertion into skin bathed with 4 mmol/L was 19.46 nmol/L. The highest theophylline concentration detected following extraction from a hydrogel-forming MN inserted for 1 h into the skin of a rat dosed orally with 10 mg/kg was of 0.363 µg/mL, whilst a maximum concentration of 0.063 µg/mL was detected following extraction from a MN inserted for 1 h into the skin of a rat dosed with 5 mg/kg theophylline. In human volunteers, the highest mean concentration of caffeine detected using MN was 91.31 µg/mL over the period from 1 to 2 h post-consumption of 100 mg Proplus® tablets. The highest mean blood glucose level was 7.89 nmol/L detected 1 h following ingestion of 75 g of glucose, while the highest mean glucose concentration extracted from MN was 4.29 nmol/L, detected after 3 hours skin insertion in human volunteers. Whilst not directly correlated, concentrations extracted from MN were clearly indicative of trends in blood in both rats and human volunteers. This work strongly illustrates the potential of hydrogel-forming MN in minimally-invasive patient monitoring and diagnosis. Further studies are now ongoing to reduce clinical insertion times and develop mathematical algorithms enabling determination of blood levels directly from MN measurements.

Retention of xenon in quartz and Earth's missing xenon.

The reactivity of xenon with terrestrial oxides was investigated by in situ synchrotron x-ray diffraction. At high temperature (T > 500 kelvin), some silicon was reduced, and the pressure stability of quartz was expanded, attesting to the substitution of some xenon for silicon. When the quartz was quenched, xenon diffused out and only a few weight percent remained trapped in samples. These results show that xenon can be covalently bonded to oxygen in quartz in the lower continental crust, providing an answer to the missing xenon problem; synthesis paths of rare gas compounds are also opened.

Influencia en la salud del rol de género / Influence of gender role on health

Se realizó un estudio descriptivo retrospectivo para determinar las diferencias de género en cuanto a características biosociales, roles productivo, reproductivo, comunitario y aspectos que afectan la salud. La muestra fue de 150 hombres y 150 mujeres, con relación matrimonial entre sí, a los cuales se les aplicó una encuesta. Los principales resultados arrojaron que el 39,3 porciento de las mujeres estaban sin ocupación laboral, los hombres tenían mayor ingreso salarial, satisfacción laboral, posibilidades de superación; las mujeres ejecutaban generalmente las labores domésticas y la planificación de la economía familiar, así como participaban en mayor medida que los hombres en actividades religiosas, y eran víctimas de maltratos físicos, psicológicos o sexuales más frecuentemente. Se concluyó que en el rol reproductivo hubo iniquidad de género desfavorable al sexo femenino, en el rol productivo hubo iniquidad de género favorable a los masculinos, en el rol de gestión comunitario hubo predominio de equidad genérica y la mujer tuvo un número mayor de variables que afectan su salud