Modelling atopic dermatitis in healthy human skin for the characterization of topical compounds.

Suitable human models for the development and characterization of topical compounds for inflammatory skin diseases such as atopic dermatitis are not readily available to date. We describe here the development of a translational model involving healthy human skin mimicking major aspects of AD and its application for the characterization of topical Janus kinase inhibitors. Full thickness human abdominal skin obtained from plastic surgery stimulated in vitro with IL4 and IL13 shows molecular features of AD. This is evidenced by STAT6 phosphorylation assessed by immunohistochemistry and analysis of skin lysates. Broad transcriptome changes assessed by AmpliSeq followed by gene set variation analysis showed a consistent upregulation of gene signatures characterizing AD in this model. Topical application of experimental formulations of compounds targeting the JAK pathway to full thickness skin normalizes the molecular features of AD induced by IL4 and IL13 stimulation. The inhibitory effects of topical JAK inhibitors on molecular features of AD are supported by pharmacokinetic analysis. The model described here is suited for the characterization of topical compounds for AD and has the potential to be extended to other inflammatory skin diseases and pathophysiological pathways.

Disruption of DNA methylation-mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice.

Orofacial clefts of the lip and palate are widely recognized to result from complex gene-environment interactions, but inadequate understanding of environmental risk factors has stymied development of prevention strategies. We interrogated the role of DNA methylation, an environmentally malleable epigenetic mechanism, in orofacial development. Expression of the key DNA methyltransferase enzyme DNMT1 was detected throughout palate morphogenesis in the epithelium and underlying cranial neural crest cell (cNCC) mesenchyme, a highly proliferative multipotent stem cell population that forms orofacial connective tissue. Genetic and pharmacologic manipulations of DNMT activity were then applied to define the tissue- and timing-dependent requirement of DNA methylation in orofacial development. cNCC-specific Dnmt1 inactivation targeting initial palate outgrowth resulted in OFCs, while later targeting during palatal shelf elevation and elongation did not. Conditional Dnmt1 deletion reduced cNCC proliferation and subsequent differentiation trajectory, resulting in attenuated outgrowth of the palatal shelves and altered development of cNCC-derived skeletal elements. Finally, we found that the cellular mechanisms of cleft pathogenesis observed in vivo can be recapitulated by pharmacologically reducing DNA methylation in multipotent cNCCs cultured in vitro. These findings demonstrate that DNA methylation is a crucial epigenetic regulator of cNCC biology, define a critical period of development in which its disruption directly causes OFCs, and provide opportunities to identify environmental influences that contribute to OFC risk.

Manuka oil based ECMT-154 versus vehicle control for the topical treatment of eczema: study protocol for a randomised controlled trial in community pharmacies in Aotearoa New Zealand.

BACKGROUND: Eczema is a chronic, relapsing skin condition commonly managed by emollients and topical corticosteroids. Prevalence of use and demand for effective botanical therapies for eczema is high worldwide, however, clinical evidence of benefit is limited for many currently available botanical treatment options. Robustly-designed and adequately powered randomised controlled trials (RCTs) are essential to determine evidence of clinical benefit. This protocol describes an RCT that aims to investigate whether a manuka oil based emollient cream, containing 2% ECMT-154, is a safe and effective topical treatment for moderate to severe eczema. METHODS: This multicentre, single-blind, parallel-group, randomised controlled trial aims to recruit 118 participants from community pharmacies in Aotearoa New Zealand. Participants will be randomised 1:1 to receive topical cream with 2% ECMT-154 or vehicle control, and will apply assigned treatment twice daily to affected areas for six weeks. The primary outcome is improvement in subjective symptoms, assessed by change in POEM score. Secondary outcomes include change in objective symptoms assessed by SCORAD (part B), PO-SCORAD, DLQI, and treatment acceptability assessed by TSQM II and NRS. DISCUSSION: Recruitment through community pharmacies commenced in January 2022 and follow up will be completed by mid-2023. This study aims to collect acceptability and efficacy data of manuka oil based ECMT-154 for the treatment of eczema. If efficacy is demonstrated, this topical may provide an option for a novel emollient treatment. The community-based design of the trial is anticipated to provide a generalisable result. ETHICS AND DISSEMINATION: Ethics approval was obtained from Central Health and Disability Ethics Committee (reference: 2021 EXP 11490). Findings of the study will be disseminated to study participants, published in peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001096842. Registered on August 18, 2021 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382412&isReview=true ). PROTOCOL VERSION: 2.1 (Dated 18/05/2022).

Preventing liver disease with policy measures to tackle alcohol consumption and obesity: The HEPAHEALTH II study.

BACKGROUND & AIMS: Chronic liver disease (CLD) causes 1.8% of all deaths in Europe, many of them from liver cancer. We estimated the impact of several policy interventions in France, the Netherlands, and Romania. METHODS: We used a validated microsimulation model to assess seven different policy scenarios in 2022-2030: a minimum unit price (MUP) of alcohol of €0.70 or €1, a volumetric alcohol tax, a sugar-sweetened beverage (SSB) tax, food marketing restrictions, plus two different combinations of these policies compared against current policies (the 'inaction' scenario). RESULTS: All policies reduced the burden of CLD and liver cancer. The largest impact was observed for a MUP of €1, which by 2030 would reduce the cumulative incidence of CLD by between 7.1% to 7.3% in France, the Netherlands, and Romania compared with inaction. For liver cancer, the corresponding reductions in cumulative incidence were between 4.8% to 5.8%. Implementing a package containing a MUP of €0.70, a volumetric alcohol tax, and an SSB tax would reduce the cumulative incidence of CLD by between 4.29% to 4.71% and of liver cancer by between 3.47% to 3.95% in France, the Netherlands, and Romania. The total predicted reduction in healthcare costs by 2030 was greatest with the €1 MUP scenario, with a reduction for liver cancer costs of €8.18M and €612.49M in the Netherlands and France, respectively. CONCLUSIONS: Policy measures tackling primary risk factors for CLD and liver cancer, such as the implementation of a MUP of €1 and/or a MUP of €0.70 plus SSB tax could markedly reduce the number of Europeans with CLD or liver cancer. IMPACT AND IMPLICATIONS: Policymakers must be aware that alcohol and obesity are the two leading risk factors for chronic liver disease and liver cancer in Europe and both are expected to increase in the future if no policy interventions are made. This study assessed the potential of different public health policy measures to mitigate the impact of alcohol consumption and obesity on the general population in three European countries: France, the Netherlands, and Romania. The findings support introducing a €1 minimum unit price for alcohol to reduce the burden of chronic liver disease. In addition, the study shows the importance of targeting multiple drivers of alcohol consumption and obesogenic products simultaneously via a harmonized fiscal policy framework, to complement efforts being made within health systems. These findings should encourage policymakers to introduce such policy measures across Europe to reduce the burden of liver disease. The modeling methods used in this study can assist in structuring similar modeling in other regions to expand on this study's findings.

Understanding the needs of women undergoing breast ultrasound: Are male radiologists still needed?

INTRODUCTION: A trend towards less male radiologists specializing in breast ultrasound was observed. A common notion in the field of breast radiology is, that female patients feel more comfortable being treated by female radiologists. The aim of the study was to understand and report the needs of women undergoing breast ultrasound with regards to the sex of the radiologist performing the investigation. METHODS: Informed consent was obtained from all patients prior to inclusion in a prospective bi-center quality study. At center 1 (72 patients), the women were examined exclusively by female radiologists, at center 2 (100 patients) only by male radiologists. After the examination the patients were asked about their experiences and their wishes for the future. RESULTS: Overall, women made no distinction between female and male radiologists; 25% of them wanted a female radiologist and 1.2% wanted a male radiologist. The majority (74%) stated that it made no difference whether a female or male radiologist performed the examination. The majority of women in group 2, who were investigated exclusively by male radiologists, stated that they had no preferences with regard to the sex of the radiologist (93%); 5% of the women wished to be investigated solely by a female radiologist and 2% exclusively by a male radiologist. DISCUSSION: The majority of women undergoing breast ultrasound are unconcerned about the radiologist's sex. It would appear that women examined by male radiologists are less selective about the sex of the examining radiologist. TRIAL REGISTRATION: Written informed consent was obtained from all patients. All patient data were anonymized. The physicians had no access to any further personal data. National regulations did not require dedicated ethics approval with anonymized lists or retrospective questionnaires.

Pharmacokinetic analysis of acute and dietary exposure to piperonyl butoxide in the mouse.

Piperonyl butoxide (PBO) is a popular insecticide synergist present in thousands of commercial, agricultural, and household products. PBO inhibits cytochrome P450 activity, impairing the ability of insects to detoxify insecticides. PBO was recently discovered to also inhibit Sonic hedgehog signaling, a pathway required for embryonic development, and rodent studies have demonstrated the potential for in utero PBO exposure to cause structural malformations of the brain, face, and limbs, or more subtle neurodevelopmental abnormalities. The current understanding of the pharmacokinetics of PBO in mice is limited, particularly with respect to dosing paradigms associated with developmental toxicity. To establish a pharmacokinetic (PK) model for oral exposure, PBO was administered to female C57BL/6J mice acutely by oral gavage (22-1800 mg/kg) or via diet (0.09 % PBO in chow). Serum and adipose samples were collected, and PBO concentrations were determined by HPLC-MS/MS. The serum concentrations of PBO were best fit by a linear one-compartment model. PBO concentrations in visceral adipose tissue greatly exceeded those in serum. PBO concentrations in both serum and adipose tissue decreased quickly after cessation of dietary exposure. The elimination half-life of PBO in the mouse after gavage dosing was 6.5 h (90 % CI 4.7-9.5 h), and systemic oral clearance was 83.3 ± 20.5 mL/h. The bioavailability of PBO in chow was 41 % that of PBO delivered in olive oil by gavage. Establishment of this PK model provides a foundation for relating PBO concentrations that cause developmental toxicity in the rodent models to Sonic hedgehog signaling pathway inhibition.

VISTA expression and patient selection for immune-based anticancer therapy.

V-domain Ig suppressor of T-cell activation (VISTA) is a B7 family member that plays key roles in maintaining T cell quiescence and regulation of myeloid cell populations, which together establish it as a novel immunotherapy target for solid tumors. Here we review the growing literature on VISTA expression in relation to various malignancies to better understand the role of VISTA and its interactions with both tumor cells and immune cells expressing other checkpoint molecules within the tumor microenvironment (TME). The biology of VISTA creates several mechanisms to maintain the TME, including supporting the function of myeloid-derived suppressor cells, regulating natural killer cell activation, supporting the survival of regulatory T cells, limiting antigen presentation on antigen-presenting cells and maintaining T cells in a quiescent state. Understanding these mechanisms is an important foundation of rational patient selection for anti-VISTA therapy. We provide a general framework to describe distinct patterns of VISTA expression in correlation with other known predictive immunotherapy biomarkers (programmed cell death ligand 1 and tumor-infiltrating lymphocytes) across solid tumors to facilitate investigation of the most efficacious TMEs for VISTA-targeted treatment as a single agent and/or in combination with anti-programmed death 1/anti-cytotoxic T lymphocyte antigen-4 therapies.

Changes in Personal Protective Equipment Practices of Craniofacial Surgeons during COVID-19: A Cross-sectional Study.

Surgeons who operate around nasal or oral airways are at particularly high risk for transmission of the severe acute respiratory syndrome coronavirus 2. This multipart study explores the changes in craniofacial surgeon preferences and practices for personal protective equipment (PPE) over the course of a worldwide pandemic. Methods: Two identical electronic survey studies, one in 2020 and one in 2022, were conducted on the use of PPE before, during, and after the pandemic among active craniomaxillofacial surgeons. Statistical changes in behaviors and preferences and differences across time points and demographic groups were evaluated. Results: The initial study included responses from 48 surgeons, and the follow-up study consisted of 36 responses. Although only 4.3% of surgeons wore N95 masks or powered air purifying respirator for craniomaxillofacial operations before the pandemic, 91.5% wore these measures during the early pandemic (P < 0.001). However, this fell to 74.3% 2 years later. Similarly, more than 95% of surgeons wore a mask in clinic during the pandemic at both time points compared to only 40.3% before the pandemic (P < 0.001). In 2020, 31.9% of surgeons planned to continue using N95 masks or powered air purifying respirator for craniofacial cases after the pandemic was over, but that fell to 11.4% in the follow-up study. Conclusions: Craniofacial surgeon practices have shifted significantly toward more protective PPE over the course of the coronavirus disease 2019 pandemic. However, this effect was dampened over the course of a protracted pandemic. Despite this, our studies indicate a long-term shift in surgeon preference that is likely to persist after the pandemic is over.

Talar neck and body fracture outcomes: a multicentre retrospective review.

PURPOSE: Talar neck and body fractures are uncommon injuries that are challenging to manage with high reported complication rates, including post-traumatic arthritis, avascular necrosis, and poor functional outcomes. The aim of this study was to assess the complication rates for patients with talus fractures across three major trauma centres (MTCs) in England. METHODS: A retrospective analysis was performed of prospectively collected trauma databases. Data were collected from three English MTCs. Patients with talar neck and/or body fractures sustained between August 2015 and August 2019 were identified and their clinical course reviewed radiologically and clinically. Isolated process fractures, osteochondral defects and paediatric patients were excluded. Patients were analysed by fracture type and for definitive treatment method with separation into non-operative and operative management groups. Procedure type was identified in the operative group. Superficial infection, deep infection, non-union, avascular necrosis, post-traumatic arthritis and removal of metalwork rates were analysed. RESULTS: Eighty-five patients with talar neck and/or body fractures were included. Seventy-five patients received operative management, 10 non-operative. The overall AVN rate was 5.9% (five patients), overall post-traumatic arthritis rate was 18.8% (16 patients), deep infection rate 1.2% (one patient), non-union rate 4.7% (four patients). Removal of metalwork rate was 9.4% (eight patients). CONCLUSION: Our reported outcomes and complication rates are generally lower than those previously described. This may be a result of improved techniques, a higher frequency of open reduction with direct visualisation or by surgery occurring in centralised specialist centres.

Efectos del entrenamiento físico de pacientes con fibrilación auricular en régimen de rehabilitación cardiovascular / Effects of physical training of patients with atrial fibrillation in cardiovascular rehabilitation regimen

Introducción: Aun son escasos los estudios que recomiendan los pacientes con fibrilación auricular en los programas de rehabilitación cardiaca. Objetivo: Evaluar los efectos del entrenamiento físico en pacientes con fibrilación auricular en régimen de rehabilitación cardiovascular. Metodología: Se realizó un estudio pre-experimental, prospectivo, tipo pretest- postest con 18 pacientes con fibrilación auricular que asistieron durante 12 semanas a las sesiones de rehabilitación cardiaca. Se evaluó el paciente al inicio y finaldel programa con ergometría con gases espirados, análisis de sangre y ecocardiograma transtorácico. Resultados: Predominaron el sexo masculino (72.2 %), el diagnóstico de miocardiopatías (33.3 %), la hipertensión arterial (100 %) y la fibrilación auricular persistente de larga duración (55.6 %). Se encontró una diferencia estadísticamente significativa para cada variable morfofuncional: índice de masa corporal (28.0±5.0 vs. 26.9±4.4, p< 0.0001), consumo de oxígeno pico (13.6±3.0 vs. 15.3±2.9, p<0.0001), consumo de oxígeno en el umbral anaerobio (9.9±2.2 vs. 10.7±2.0; p=0.007), equivalente ventilatorio para dióxido de carbono (27.7±4.7 vs. 26.6±4.7; p<0.0001), equivalente ventilatorio para el oxígeno (24.2±5.0 vs. 23.8±4.9 p=0.001), pulso de oxígeno (10.2±2.5 vs. 12.1±2.1; p< 0,0001), unidades metabólicas (3.8±0.9 vs. 4.3±0.9; p<0.0001) y fracción de eyección ventricular izquierda (55,7±8,7 vs. 58,2±7,5, p=0,003). Las variables metabólicas disminuyeron significativamente (p<0.0001). La clase funcional de Weber mejoró en 5 pacientes (27.8 %). Conclusiones: El entrenamiento físico de pacientes con fibrilación auricular durante 12 semanas de rehabilitación cardiovascular mejoró la capacidad funcional, con incrementos evolutivos de la fracción de eyección ventricular izquierda y disminución de las variables metabólicas, sin generar riesgos ni complicaciones.

Effects of physical training of patients with atrial fibrillation in cardiovascular rehabilitation regimen Introduction: There are still few studies that recommend patients with atrial fibrillation in cardiovascular rehabilitation programs. Objective: To evaluate the effects of physical training in patients with atrial fibrillation undergoing cardiovascular rehabilitation. Method: A pre-experimental, prospective, pretest-posttest study was carried out with 18 patients with atrial fibrillation who attended cardiac rehabilitation sessions for 12 weeks. The patient was evaluated at the beginning and end of the program with stress test with expired gases, blood test and transthoracic echocardiogram. Results: The male sex (72.2%), the diagnosis of cardiomyopathies (33.3%), arterial hypertension (100%) and longterm persistent atrial fibrillation (55.6%) predominated. A statistically significant difference was found for each morphofunctional variable: body mass index (28.0±5.0 vs. 26.9±4.4, p<0.0001), peak oxygen consumption (13.6±3.0 vs. 15.3±2.9, p<0.0001), oxygen at the anaerobic threshold (9.9±2.2 vs. 10.7±2.0; p=0.007), ventilatory equivalent for carbon dioxide (27.7±4.7 vs. 26.6±4.7; p<0.0001), ventilatory equivalent for oxygen (24.2± 5.0 vs. 23.8±4.9 p=0.001), oxygen pulse (10.2±2.5 vs. 12.1±2.1; p<0.0001), metabolic units (3.8±0.9 vs. 4.3±0.9; p<0.0001) and fraction of left ventricular ejection (55.7±8.7 vs. 58.2±7.5, p=0.003). The metabolic variables decreased significantly (p<0.0001). Weber's functional class improved in 5 patients (27.8%). Conclusions: Physical training of patients with atrial fibrillation during 12 weeks of cardiovascular rehabilitation improved functional capacity, with progressive increases in left ventricular ejection fraction and decrease in metabolic variables, without generating risks or complications.

Phenylephrine versus cafedrine/theodrenaline (Akrinor) for the treatment of spinal anaesthesia-induced maternal hypotension during caesarean section: a retrospective single-centre cohort study.

OBJECTIVE: The main objective of this study was to assess the impact of phenylephrine and cafedrine/theodrenaline on the mother and newborn after spinal anaesthesia for caesarean section. SETTING: University teaching hospital. DESIGN: A single-centre retrospective data cohort study. PATIENTS: All obstetric patients who were scheduled for caesarean section in a 2-year period. INTERVENTIONS: Administration of either intravenous phenylephrine prophylactically or cafedrine/theodrenaline (Akrinor) reactively to maintain blood pressure after spinal anaesthesia. MAIN OUTCOME MEASURE: Maternal hypotension, heart rate during caesarean section and after admission to IMC, fetal arterial cord pH and base excess levels, maternal volume resuscitation and the use of rescue medication. RESULTS: 852 data sets could be included: n=440 Akrinor, n=412 in the phenylephrine cohort. During caesarean section blood pressure was slightly higher in the phenylephrine group compared with the Akrinor group, while hypotension <100 mm Hg systolic blood pressure (SBP) occurred significantly more often during arrival at the IMC after surgery when phenylephrine was used. Heart rate was lower and rescue medication was significantly more frequently given in the phenylephrine cohort. Irrespective of the medication used, women with baseline levels of <120 mm Hg SBP had a high risk to develop hypotension <100 mm Hg after spinal anaesthesia for caesarean section. While there was no statistical difference in mean umbilical arterial pH levels, the incidence of acidosis, defined as pH <7.2, was significantly higher with phenylephrine. CONCLUSION: Phenylephrine was not superior to Akrinor to treat spinal anaesthesia-induced maternal hypotension during caesarean section. TRIAL REGISTRATION NUMBER: DRKS00025795.

Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial.

BACKGROUND: Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. METHODS: PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. FINDINGS: We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. INTERPRETATION: In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited. FUNDING: Accuray.

Mispositioned Hydrus Microstents: A Case Series Imaged with NIDEK GS-1 Gonioscope.

Introduction. The Hydrus microstent has become a common procedure in glaucoma surgery intended to improve outcomes of cataract surgery to lower intraocular pressure. Despite proper placement, this device can subsequently be noted to not be in the proper position. In this case series, we report mispositioned Hydrus microstents in five different patients and use NIDEK GS-1 gonioscopy. Case Report. We report five different patients who had cataract surgery and who were subsequently noted to have mispositioned Hydrus stents. No stents needed to be removed. All patients had improved vision and stable visual fields, and none required secondary surgery. Management and Outcome. In each case of mispositioned stents, vision was significantly improved and there was no inflammation or other complications noted. Discussion. Hydrus stents can be noted to be mispositioned during the post-operative period after successful insertion. This can often be well tolerated requiring no further intervention.

Ovarian Vein Thrombosis in a Non-Puerperal Patient.

Ovarian vein thrombosis (OVT) is a relatively rare, but serious disease more commonly seen in puerperal patients. In the postpartum period, there is an unequal incidence of OVT in women with vaginal delivery (0.18%) and caesarean section (2.0%). OVT is usually associated with other conditions like pelvic inflammatory disease, malignant tumours, sepsis, enteritis, and recent pelvic or abdominal surgery. The incidence of idiopathic OVT is extremely rare and only a few cases have been reported to date in healthy patients with unknown aetiology. Patients with OVT present with abdominal pain, nausea, vomiting, fever or abdominal mass. Complications of OVT include pulmonary embolism, ovarian infarction, sepsis and death. CT scanning of the abdomen provides reliable evidence for the diagnosis of idiopathic OVT. Thrombus in most patients with idiopathic OVT is located in the right ovarian vein. This may be due to the longer length of the right ovarian vein, right shift of the uterus and relative insufficiency of the right ovarian vein valve. Treatment of OVT includes systemic anticoagulation which will achieve resolution of symptoms and prevent life-threatening complications. Our case report documents a non-puerperal patient who underwent hysterectomy a year before presenting to the ED with complaints of diarrhoea and found to have OVT on a CT scan. Our case brings attention to the fact that OVT can occur outside the puerperium and might present as a rare complication of minimally invasive surgeries for endometrial cancer. Furthermore, we posit that OVT in the non-puerperal patient may be a separate clinical entity. LEARNING POINTS: Ovarian vein thrombosis (OVT) can occur outside the puerperium and might present as a rare complication of minimally invasive surgeries.OVT should be included in the differential diagnosis of a non-puerperal postoperative woman presenting with vague abdominal symptoms.Duration of anti-coagulation varies from case to case. More research is needed to determine its exact duration.

Efficacy of a 3% Kanuka oil cream for the treatment of moderate-to-severe eczema: A single blind randomised vehicle-controlled trial.

Background: Maori, the indigenous people of New Zealand, have traditionally used the kanuka tree as part of their healing system, Rongoa Maori, and the oil from the kanuka tree has demonstratable anti-inflammatory and anti-bacterial properties. This trial investigated the efficacy and safety of a 3% kanuka oil (KO) cream compared to vehicle control (VC) for the topical treatment of eczema. The trial was conducted through a nationwide community pharmacy research network. Methods: This single-blind, parallel-group, randomised, vehicle-controlled trial was undertaken in 11 research trained community pharmacies across New Zealand. Eighty adult participants with self-reported moderate-to-severe eczema, assessed by Patient Orientated Eczema Measure (POEM) were randomised by blinded investigators to apply 3% KO cream or VC topically, twice daily, for six weeks. Randomisation was stratified by site and eczema severity, moderate versus severe. Primary outcome was difference in POEM scores at week six between groups by intention to treat. The study is registered on the Australian New Zealand Clinical Trial Registry (ANZCTR) reference number, ACTRN12618001754235. Findings: Eighty participants were recruited between 17 May 2019 and 10 May 2021 (41 KO group, 39 VC group). Mean POEM score (standard deviation) improved between baseline and week six for KO group, 18·4 (4·4) to 6·8 (5·5), and VC group, 18·7 (4·5) to 9·8 (6·5); mean difference between groups (95% confidence interval) was -3·1 (-6·0 to -0·2), p = 0·036. There were three adverse events reported in the KO group related to the intervention and two in the control group. Interpretation: The KO group had a significant improvement in POEM score compared to VC. Rates of adverse events and withdrawals were similar between groups with no serious adverse events reported. Treatment acceptability was high for both groups across all domains. Our results suggest that in adults with moderate-to-severe eczema, the addition of KO to a daily emollient regimen led to a reduction in POEM score compared to VC. KO may represent an effective, safe, and well tolerated treatment for moderate-to-severe eczema in adults. Funding: Hikurangi Bioactives (Ruatoria, New Zealand) and HoneyLab (Tauranga, New Zealand), supported by a grant from Callaghan Innovation.

The provision of prostate cancer patient information leaflets on an electronic tablet: A further step to paperless health-care provision.

Introduction: The provision of patient information leaflets (PILs) for cancer treatment options is primarily via a paper format. PILs can now be provided on an electronic tablet with the added benefits of providing audio-visual information. Materials and Methods: Between February 2017 and August 2019, 112 patients with newly diagnosed prostate cancer (PCa) were enrolled into our prospective cohort study. The control group (n = 56) were all given PILs on a paper as the standard of care (SoC). The intervention (tablet) group (n = 56) were given the same paper PILs as that of the control group plus an electronic tablet computer with an application containing all SoC paper PILs in an electronic format and supplementary videos detailing treatments. Both groups were asked to complete a validated questionnaire (Telemedicine, Satisfaction and Usefulness questionnaire) with regard to satisfaction with care, provided information, and tablet usage. Results: The response rate for our study was 78/112 (70%). The control and tablet groups were highly satisfied with their care (91%-100% agreed or strongly agreed) and with the information they received (80%-100% agreed or strongly agreed). In the tablet group, 41/46 (89%) reported its utilization. Of those 41, 38 (92%) considered the tablet easy to use and 13 (32%) reported a preference for the paper format. Conclusions: The provision of electronic PILs in PCa treatment is an innovative method of providing oncological care, with positive feedback from our patients. With further development as a mobile application, electronic PILs may allow a more environmentally and fiscally advantageous method of providing PCa care.

Percutaneous Coronary Intervention VersusMyocardial Revascularization Surgery inMultivessel Coronary Artery Disease: Four-Year Followup.

INTRODUCTION: In Cuba, 29,939 deaths from ischemic heart disease were recorded in 2020. Myocardial revascularization surgery and percutaneous coronary intervention are well-established methods of treating patients with multivessel coronary artery disease. These methods can reduce overall deaths, but choosing the optimal strategy for treating left main coronary ischemia is a source of debate among specialists. OBJECTIVE: Estimate survival and major cardiac and cerebrovascular events in patients treated with percutaneous coronary intervention versus myocardial revascularization surgery and their relationships with pre-existing patients' clinical and angiographic characteristics. METHODS: We conducted a retrospective cohort study in 41 patients; 35 men and 6 women aged 40-85 years who had been diagnosed with multivessel coronary artery disease and treated with percutaneous coronary intervention (n = 17) or myocardial revascularization surgery (n = 24) at the Medical-Surgical Research Center in Havana, Cuba, in 2016. The main variable under consideration was the occurrence of major adverse cardiovascular events over a four-year period following these interventions. We collected clinical and angiographic characteristics, and used the Kaplan-Meier test to calculate survival curves. Survival probabilities were compared using the log-rank test. A value of p ⟨ 0.05 was considered statistically significant. The Cox proportional hazards model was used to estimate the hazard ratio, with 95% confidence intervals used for both procedures. RESULTS: There were a total of 20 major adverse cardiovascular events, 75% (15/20) of which occurred in patients who underwent percutaneous coronary intervention and 5% in patients who had myocardial revascularization surgery. The probability of survival was 70.6% in surgery and 37.5% in interventionism; p = 0.043; hazard ratio 1.58 (95% confidence interval 0.987-2.530), p = 0.047. The need to repeat a revascularization procedure was the only major cardiovascular event that showed significant differences between methods (log-rank p = 0.015), and was more frequent in percutaneous intervention. CONCLUSIONS: Myocardial revascularization surgery offers a better chance of survival than percutaneous coronary intervention. Major adverse cardiovascular events are more frequent in patients with coronary interventionism, due to the need to repeat revascularization.

Clinical Implication of Phosphodiesterase-4-Inhibition.

The pleiotropic function of 3',5'-cyclic adenosine monophosphate (cAMP)-dependent pathways in health and disease led to the development of pharmacological phosphodiesterase inhibitors (PDE-I) to attenuate cAMP degradation. While there are many isotypes of PDE, a predominant role of PDE4 is to regulate fundamental functions, including endothelial and epithelial barrier stability, modulation of inflammatory responses and cognitive and/or mood functions. This makes the use of PDE4-I an interesting tool for various therapeutic approaches. However, due to the presence of PDE4 in many tissues, there is a significant danger for serious side effects. Based on this, the aim of this review is to provide a comprehensive overview of the approaches and effects of PDE4-I for different therapeutic applications. In summary, despite many obstacles to use of PDE4-I for different therapeutic approaches, the current data warrant future research to utilize the therapeutic potential of phosphodiesterase 4 inhibition.

Synergistic Effects of Surface Coating and Bulk Doping in Ni-Rich Lithium Nickel Cobalt Manganese Oxide Cathode Materials for High-Energy Lithium Ion Batteries.

Ni-rich layered oxide cathodes are promising candidates to satisfy the increasing energy demand of lithium-ion batteries for automotive applications. Thermal and cycling stability issues originating from increasing Ni contents are addressed by mitigation strategies such as elemental bulk substitution ("doping") and surface coating. Although both approaches separately benefit the cycling stability, there are only few reports investigating the combination of two of such approaches. Herein, the combination of Zr as common dopant in commercial materials with effective Li2 WO4 and WO3 coatings was investigated with special focus on the impact of different material processing conditions on structural parameters and electrochemical performance in nickel-cobalt-manganese (NCM) || graphite cells. Results indicated that the Zr4+ dopant diffusing to the surface during annealing improved the electrochemical performance compared to samples without additional coatings. This work emphasizes the importance to not only investigate the effect of individual dopants or coatings but also the influences between both.

Gender-related Differences in the Impact of COVID-19 Pandemic in Cardiometabolic Patients in Latin America: The CorCOVID LATAM Gender Sub-study.

COVID-19 pandemic and lockdown measures have disrupted lifestyle habits and self-care. Gender differences in health behavior during the pandemic have not yet been fully elucidated. The aim of this study was to evaluate gender related differences in the impact of COVID-19 pandemic on patients with cardiometabolic diseases. A cross-sectional survey was administered to cardiometabolic patients in 13 Latin American countries between June 15th and July 15th, 2020. The study included 4216 participants, of which 2147 (50.9%) were women. Women reported healthier eating habits as well as lower tobacco and alcohol consumption than men but exercised less and reported increased symptoms of depression. Low income and symptoms of depression were associated with sedentarism in women. The interplay between psychological factors and sedentarism could increase the risk of cardiovascular events in this population.