Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force.

OBJECTIVE: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. METHODS: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. RESULTS: The Task Force proposed two definitions of remission: 'cSLE clinical remission on steroids (cCR)' and 'cSLE clinical remission off steroids (cCR-0)'. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0-3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. CONCLUSIONS: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

Megalencephaly secondary to a novel germline missense variant p.Asp322Tyr in AKT3 associated with growth hormone deficiency and central hypothyroidism: A case report.

Germline gain of function variations in the AKT3 gene cause brain overgrowth syndrome with megalencephaly and diffuse bilateral cortical malformations. Here we report a child with megalencephaly, who is a carrier of a novel heterozygous missense variant in the AKT3 gene NM_005465.7:c.964G>T,p.Asp322Tyr. The phenotype of this patient is associated with pituitary deficiencies diagnosed at 2 years of age: growth hormone (GH) deficiency responsible for growth delay and central hypothyroidism. After 6 months of GH treatment, intracranial hypertension was noted, confirmed by the observation of papilledema and increased intracranial pressure, requiring the initiation of acetazolamide treatment and the discontinuation of GH treatment. This is the second reported patient described with megalencephaly and AKT3 gene variant associated with GH deficiency . Other endocrine disorders have also been reported in few cases with hypothyroidism and hypoglycemia. Pituitary deficiency may be a part of the of megalencephaly phenotype secondary to germline variant in the AKT3 gene. Special attention should be paid to growth in these patients and search for endocrine deficiency is necessary in case of growth retardation or hypoglycemia.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).

OBJECTIVE: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. METHODS: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. RESULTS: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. CONCLUSIONS: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

Challenges and opportunities of sharing animal health data for research and disease management: a case study of bovine tuberculosis.

The sharing of animal disease data should be encouraged. The analysis of such data will broaden our knowledge of animal diseases and potentially provide insights into their management. However, the need to conform to data protection rules in the sharing of such data for analysis purposes often poses practical difficulties. This paper sets out the challenges and the methods used for the sharing of animal health data in England, Scotland and Wales - Great Britain - using bovine tuberculosis (bTB) data as a case study. The data sharing described is undertaken by the Animal and Plant Health Agency on behalf of the Department for Environment, Food and Rural Affairs and the Welsh and Scottish Governments. It should be noted that animal health data are held at the level of Great Britain (rather than the United Kingdom - which includes Northern Ireland), as Northern Ireland's Department of Agriculture, Environment and Rural Affairs has its own separate data systems. Bovine tuberculosis is the most significant and costly animal health problem facing cattle farmers in England and Wales. It can be devastating for farmers and farming communities and the control costs for taxpayers in Great Britain are over £150 million a year. The authors describe two methods of data sharing - first, where data are requested by, and delivered to, an academic institution for epidemiological or scientific analysis, and second, where data are proactively published in an accessible and meaningful way. They provide details of an example of the second method, namely, the free-to-access website â€Ëœinformation bovine TB' (https://ibtb.co.uk), which publishes bTB data for the benefit of the farming community and veterinary health professionals.

L'échange et le partage de données sur les maladies animales sont des pratiques à encourager. En effet, l'analyse de ces données permet d'étoffer les connaissances sur les maladies animales et peut aussi apporter un nouvel éclairage sur leur gestion. Néanmoins, la nécessité de se conformer aux règles sur la protection des données pose souvent des difficultés pratiques lors des échanges de ce type de données à des fins d'analyse. Les auteurs expliquent les difficultés rencontrées en matière d'échange de données de santé animale en Angleterre, en écosse et au Pays de Galles (Grande-Bretagne), ainsi que les méthodes utilisées, à partir de l'exemple concret des données relatives à la tuberculose bovine. L'échange et le partage de données sont réalisés par l'Agence britannique de santé animale et végétale, pour le compte du ministère britannique de l'Environnement, de l'Alimentation et des Affaires rurales et des gouvernements gallois et écossais. Il convient de préciser que les données de santé animale dont il s'agit sont celles conservées au niveau de la Grande-Bretagne seulement (et non du Royaume-Uni, qui inclut l'Irlande du Nord), étant donné que le ministère de l'Agriculture, de l'Environnement et des Affaires rurales de l'Irlande du Nord possède ses propres systèmes de données. La tuberculose bovine est le principal problème de santé animale auquel sont confrontés les éleveurs de bovins en Angleterre et au Pays de Galles, et le plus coûteux à traiter. La survenue de la tuberculose bovine est une catastrophe pour les éleveurs affectés et leur communauté. En outre, le coût annuel de son contrôle s'élève à plus de 150 millions de livres pour le contribuable britannique. Les auteurs décrivent deux méthodes d'échange et de partage de données : la première est celle où une institution de recherche demande et obtient l'accès à des données particulières afin de réaliser une étude épidémiologique ou scientifique ; la deuxième consiste à publier les données de manière proactive et constructive, en les rendant facilement accessibles. Un exemple concret de cette deuxième méthode est décrit en détail : il s'agit du site web d'information sur la tuberculose bovine (https://ibtb.co.uk), d'accès libre, qui diffuse des informations sur cette maladie à l'intention des éleveurs et des professionnels de la santé animale.

Convendría alentar la puesta en común de datos zoosanitarios, pues el análisis de estos datos nos ayudará a conocer más y mejor las enfermedades animales y, a la postre, puede darnos pistas sobre la mejor manera de afrontarlas. Ocurre a menudo, sin embargo, que el prescriptivo cumplimiento de las reglas de protección de datos plantee dificultades prácticas para poner estos datos en común con fines de análisis. Los autores, empleando como ejemplo un estudio sobre la tuberculosis bovina, describen esas dificultades y los métodos utilizados para compartir datos zoosanitarios en Inglaterra, Escocia y Gales (Gran Bretaña). En el ejemplo descrito, la Agencia de Sanidad Animal y Vegetal del Reino Unido fue la instancia que impulsó la puesta en común de los datos en nombre del Departamento de Medio Ambiente, Alimentación y Asuntos Rurales del Reino Unido y de los gobiernos galés y escocés. Conviene puntualizar que los datos zoosanitarios cubren el territorio de Gran Bretaña (y no de todo el Reino Unido, que incluye Irlanda del Norte), ya que el Departamento de Medio Ambiente, Alimentación y Asuntos Rurales norirlandés dispone de su propio sistema de datos independiente. La tuberculosis bovina es el problema zoosanitario más importante y oneroso al que hacen frente las explotaciones de vacuno en Inglaterra y Gales. Esta enfermedad no solo puede ser devastadora para los productores y profesionales del sector, sino que la lucha contra ella cuesta al contribuyente británico más de 150 millones de libras al año. Los autores describen dos métodos para compartir de datos: en el primero de ellos, un establecimiento universitario solicita y recibe los datos con fines de análisis científico o epidemiológico; en el segundo, una entidad toma la iniciativa de hacer públicos los datos de forma accesible y coherente. Los autores exponen en detalle un ejemplo del segundo procedimiento, a saber, el sitio web de información sobre la tuberculosis bovina (https://ibtb.co.uk) en libre acceso, en el cual se publican datos sobre la enfermedad dirigidos a los profesionales del sector pecuario y la sanidad animal.

[Ordalie, sensation-seeking and impulsivity. Critical analysis of definitions]. / Ordalie, recherche de sensations et impulsivité. Analyse critique des définitions.

BACKGROUND: In the fields of psychology and psychiatry, the use of the terms impulsivity, sensation-seeking and ordalie to refer to risk-taking behaviors can sometimes be confusing. OBJECTIVE: The objective of this study was to establish a clinical definition of the concepts of ordalie, sensation-seeking and impulsivity, in order to analyze the similarities and differences between these concepts. METHODS: We prioritized literature review articles with or without meta-analysis from the Medline database and supplemented with the Google-Scholar database. The articles were included in this review if their objectives were in line with ours. The research was conducted in November 2018. RESULTS: Twenty-seven articles were selected. There are similarities in the clinical definitions of these concepts with measurable heterogeneous constructions, and an exacerbation in adolescence for engagement in harmful behaviors, but there are also nuances that highlight their differences. CONCLUSION: We were able to describe areas of divergence and convergence between these three concepts but not to establish a quantitative diagram of the areas of divergence and convergence. It would seem that the coexistence of sensation-seeking and impulsivity in the same individual could explain that individual's involvement in ordalique behaviors. Further studies approaching this hypothesis would seem useful in terms of preventing risk-taking behaviors such as addictive behaviors.

Prioritisation of areas for early detection of southward movement of arctic fox rabies based on historical surveillance data in Quebec, Canada.

Arctic rabies virus variant (ARVV) is enzootic in Quebec (Canada) north of the 55th parallel. With climate change, increased risk of re-incursion of ARVV in more densely populated southern regions raises public and animal health concerns. The objective of this study was to prioritise geographical areas to target for an early detection of ARVV incursion south of the 55th parallel based on the historical spatio-temporal trends of reported rabies in foxes in Quebec. Descriptive analyses of fox rabies cases from 1953 to 2017 were conducted. Three periods show increases in the number of fox rabies cases in southern regions and indicate incursion from northern areas or neighbouring provinces. The available data, particularly in central and northern regions of the province, were scarce and of low spatial resolution, making it impossible to identify the path of spread with precision. Hence, we investigated the use of multiple criteria, such as historical rabies cases, human population density and red fox (Vulpes vulpes) relative abundance, to prioritise areas for enhanced surveillance. This study underscores the need to define and maintain new criteria for selecting samples to be analysed in order to detect rapidly ARVV cases outside the current enzootic area and any potential re-incursion of the virus into central and southern regions of the province.

Development of vascular substitutes for low-flow peripheral bypass grafting - a review.

The development of a low-flow vascular prosthesis is a very topical issue. The authors present a pathway for the development of a prosthesis with optimal properties based on the idea of mimicking the characteristics of a biological model (saphenous vein graft) and programming these properties in the model of the prosthetic substitute. The vascular prosthesis presented consists of three layers - a non-absorbable scaffold representing vascular “media”, and two absorbable collagen layers - pseudointima and pseudoadventitia. The basic methods of physical testing are presented - the single axis stretch test and inflation-extension test, as well as other procedures that affect the final properties. These include collagen curing, antithrombotic treatment of the inner layer and the use of sterilization methods. The designed new graft was successfully implanted in an ovine model.

Dunbar syndrome - single-center experience with surgical treatment.

INTRODUCTION: Dunbar syndrome is caused by compression of the truncus coeliacus (TC), most commonly by the median arcuate ligament. Chronic irritation of the TC during breathing leads to fibrous changes of the arterial wall and formation of fixed stenosis. This compression syndrome is often associated with specific complaints including weight loss and early postprandial epigastric pain. In this study, we summarize our experience with a group of 14 patients from a single institution. METHODS: In 14 patients who were diagnosed with Dunbar syndrome and who were referred for surgery, we performed an invasive measurement of systemic pressure in a. radialis during the operation and compared it with invasively measured pressure in a. gastrica sinistra before and after the release of TC. In patients with significant stenosis (pressure gradient above 15 mmHg), a bypass was performed. RESULTS: The initial pressure gradient of 56±19 mmHg decreased after the release of TC to 39±16 mmHg (p.

Concomitant embolism in the subclavian and pulmonary artery.

INTRODUCTION: Pulmonary embolism is a life-threatening condition that causes obstruction of the pulmonary arteries by an embolus, most often originating from the venous system of the lower limbs or pelvic veins. Depending on the extent of the embolism, an acute right-sided heart failure may result, with subsequent death. Paradoxical embolism is a condition in which a venous thrombus is embolized into the systemic circulation arteries by a right-to-left heart shunt. This condition most commonly occurs in the interatrial septum. The aim of treatment for pulmonary embolism is to remove the obstruction of the lung. Depending on the extent of the embolism and the patients hemodynamic status, thrombolytic or surgical treatment can be chosen. Thrombolytic therapy has become the basis of treatment for all types of acute pulmonary embolism. Currently, open surgery is indicated in hemodynamically unstable patients with massive pulmonary embolism, and increasingly frequently in submassive embolism where thrombolytic therapy is not effective or contraindicated. CASE REPORT: The case report describes a less common condition of pulmonary and concurrently systemic embolization in the subclavian artery. Thrombolytic therapy was contraindicated in this case due to the high risk of secondary embolism to the brain. Surgical embolectomy was performed from the pulmonary arteries simultaneously with direct embolectomy from the subclavian and brachiocephalic artery. The surgical management of acute pulmonary embolism is a suitable method of treatment for both massive pulmonary embolism where the procedure is performed as a life-saving indication, and submassive embolism where less invasive treatment would not be effective. CONCLUSION: Direct embolectomy of subclavian and brachiocephalic artery is associated with minimal risk of iatrogenic embolism into the arteries supplying the brain compared to indirect embolectomy performed from the cubital or brachial artery. Key words: embolism paradoxical embolization - embolectomy foramen ovale stroke.

Branched pedal bypass in the treatment of critical limb ischemia - a single center experience.

INTRODUCTION: Pedal bypass is a therapeutic option for limb salvage in critical limb ischemia. METHOD: Retrospective analysis of 20 patients who underwent either simple (14 patients) or branched (6 patients) pedal bypass in a single center and had at least one postoperative follow-up. In patients with branched pedal bypass, the main trunk was connected to the pedal artery of better quality and the side branch to an artery on the opposite side of the foot. The main trunk was constructed as a reverse saphenous bypass in all patients with branched bypass. From patients with simple bypass, nine had reverse saphenous graft, three had an allograft, one patient had in situ saphenous graft, and one PTFE prosthesis. RESULTS: The difference in the operation time was not significant. One patient with simple bypass required reoperation for wound bleeding and there was one case of perioperative mortality in the same group. The difference between the groups in the primary or secondary patency rates, limb salvage and overall survival was not significant. CONCLUSIONS: We did not find any significant difference in patency rates, limb salvage, or perioperative complications between patients with simple and branched pedal bypass in our cohort. We believe that the anticipated benefits of constructing an additional branch are masked by the disadvantageous presence of an additional anastomosis. Adoption of a branched pedal bypass may therefore require further improvements - perhaps the utilization of a branched saphenous graft. Key words:  critical limb ischemia - peripheral arterial disease - bypass - revascularization - amputation.

Rett-like phenotypes: expanding the genetic heterogeneity to the KCNA2 gene and first familial case of CDKL5-related disease.

Several genes have been implicated in Rett syndrome (RTT) in its typical and variant forms. We applied next-generation sequencing (NGS) to evaluate for mutations in known or new candidate genes in patients with variant forms of Rett or Rett-like phenotypes of unknown molecular aetiology. In the first step, we used NGS with a custom panel including MECP2, CDKL5, FOXG1, MEF2C and IQSEC2. In addition to a FOXG1 mutation in a patient with all core features of the congenital variant of RTT, we identified a missense (p.Ser240Thr) in CDKL5 in a patient who appeared to be seizure free. This missense was maternally inherited with opposite allele expression ratios in the proband and her mother. In the asymptomatic mother, the mutated copy of the CDKL5 gene was inactivated in 90% of blood cells. We also identified a premature stop codon (p.Arg926*) in IQSEC2 in a patient with a Rett-like phenotype. Finally, exome sequencing enabled us to characterize a heterozygous de novo missense (p.Val408Ala) in KCNA2 encoding the potassium channel Kv 1.2 in a girl with infantile-onset seizures variant of RTT. Our study expands the genetic heterogeneity of RTT and RTT-like phenotypes. Moreover, we report the first familial case of CDKL5-related disease.

Utility of cardiac CT for evaluating delayed contrast enhancement in dilated cardiomyopathy.

BACKGROUND: The presence of myocardial fibrosis is associated with adverse outcome in dilated cardiomyopathy (DCM). Delayed contrast-enhanced cardiac magnetic resonance (DE-CMR) currently represents the gold standard in noninvasive evaluation of myocardial scarring. However, a significant number of patients are unable to undergo DE-CMR study for various reasons. We sought to determine the diagnostic accuracy of cardiac CT (CCT) compared with CMR in the investigation of the presence of delayed contrast enhancement (DCE) in subjects with DCM. METHODS: We prospectively enrolled 17 consecutive patients with DCM, who were initially referred to our institution because of recently manifested heart failure due to unexplained left ventricular systolic dysfunction. In all subjects, CCT and DE-CMR were performed within 1 week. RESULTS: CCT and DE-CMR showed satisfactory agreement in detecting DCE (agreement in 82% cases, κ = 0.56) with 50% sensitivity, 100% specificity, and a positive predictive value of 100%. CONCLUSION: CCT may be a valuable method for detecting DCE in patients with DCM. CCT thus might be considered as an alternative method to DE-CMR in the assessment of the presence and extent of myocardial fibrosis in subjects who are not suitable for DE-CMR examination.

[Isolated Perfusion of the Upper Extremity with TNF-α - Double Venous Cannulation]. / Izolovaná perfuze horní koncetiny s TNF-α - dvojitá kanylace zilního systému.

BACKGROUND: The authors present a technical variation of the standard cannulation for cardiopulmonary bypass perfusion during hyperthermic isolated limb perfusion (ILP) procedures in selected patients with unresectable soft tissue sarcoma or malignant melanoma. PATIENTS: Of 55 ILP procedures performed at our institution since the procedure was established in 2009, nine were performed at the upper extremity. Standard single venous cannulation was used in five cases, and extended, double venous cannulation in the last four. The standard technique for brachial vein cannulation in a small compartment of the upper extremity entails a problematic and longer perfusion of the upper extremity. This is due to the lower flow rate in the venous system and relatively large surface area with respect to weight. We present a simple technique based on a "Y" cannulation of the venous system via the deep brachial vein and superficial venous system via the basilic vein, delivering a 20% increase in flow rate in the extracorporeal circulation. Faster heating of the upper extremity and a stable thermal environment throughout upper-extremity ILP are essential for successful treatment. CONCLUSION: Extended technique of venous cannulation for extracorporeal circulation setting, due to their advantages, became standard in the upper limb ILP procedure at our institution.Key words: isolated limb perfusion - malignant melanoma - soft tissue sarcoma - upper limb - extracorporeal circulation The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 8. 1. 2017Accepted: 15. 1. 2017.

Treatment of locally advanced pancreatic cancer by percutaneous and intraoperative irreversible electroporation: general hospital cancer center experience.

The aim of this study was to evaluate the safety of irreversible electroporation (IRE) and the outcome of patients undergoing IRE of locally advanced pancreatic cancer (PC). Twenty-one patients with unresectable PC underwent open (n=19) or percutaneous (n=2) IRE of the tumor using the Nanoknife system with two electrodes that were repositioned several times to affect the whole mass. The size of the tumor was 39±10mm with a range from 21 to 65mm. Five patients underwent neoadjuvant chemotherapy and seven patients were treated with chemotherapy after IRE. Complications occurred in five patients, which resulted in prolongation of the average hospital stay from 10 to 34 days. There was no mortality in the first postoperative month. Median survival after IRE was 10.2 months compared to 9.3 months in a matched cohort (hazard ratio = .54, p = .053). The quality of life was declining slowly. 81% of time after IRE the Karnofsky performance status was ≥70 and sharp decline occurred approximately 8 weeks before death.In conclusion, IRE is a safe palliative treatment option for a percentage of patients with locally advanced pancreatic carcinoma. The patients treated with open IRE lived a decent life until 8 weeks before their death. We believe that IRE of pancreatic carcinoma can be regarded as an option, if imaging or explorative laparotomy show that R0 resection in not possible.

Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States.

BACKGROUND: The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. METHODS: A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. RESULTS: Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. CONCLUSIONS: This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Gastrointestinal complications after cardiac surgery : eight years experience in a single center.

BACKGROUND: The aim of this study was to evaluate the frequency of gastrointestinal complications (GICs) and associated risk factors in patients after cardiac surgery, and to stratify them according to the risk of developing GICs in order to improve our diagnostic protocols. METHODS: A total of 5959 patients who underwent cardiac surgery within a period of 97 months were retrospectively evaluated. Surgical procedures included coronary artery bypass grafting, heart valve surgery, aortic surgery, surgical correction of adult congenital heart defects, or combined procedures. RESULTS: The frequency of GICs was 1.3% (75 patients). Intestinal ischemia and upper or lower gastrointestinal bleeding were the most common GICs. From 27 patients affected by intestinal ischemia, 21 patients were previously treated with intra-aortic balloon pump (p < 0.001). Low cardiac output, renal failure or dysfunction, renal risk, peripheral arterial disease, history of myocardial infarction, male gender, intra-aortic balloon pump, cardiopulmonary bypass time, aortic cross-clamp time, duration of intubation, SIRS, and MODS were associated with significantly increased risk of GICs. CONCLUSIONS: To decrease the occurrence of intestinal ischemia, we suggest that placement of intra-aortic balloon pump should be preceded by examination of the descending aorta to rule out severe atherosclerotic changes, in which case -alternative cardiac support should be attempted.

ENPP1 homozygous stop-loss variant causing generalized arterial calcifications of infancy: About a severe neonatal clinical case.

Generalized Arterial Calcifications of Infancy (GACI) is an extremely rare autosomal recessive genetic condition, mostly due to pathogenic variations in the ENPP1 gene (GACI1, MIM #208000, ENPP1, MIM #173335). To date 46 likely pathogenic or pathogenic distinct variations in ENPP1 have been described, including nonsense, frameshift, missense, splicing variations, and large deletions. Here we report a case of GACI in a male newborn with a homozygous stop-loss variant in ENPP1 treated in Nancy Regional University Maternity Hospital. Based on proband main clinical signs, clinical exome sequencing was performed and showed a deletion of one nucleotide leading to frameshift and stop-loss (NM_006208.3 (ENPP1):c.2746del,p.(Thr916Hisfs*23)). Clinical presentation is characterized by primary neonatal arterial hypertension resulting in hypertrophic cardiomyopathy decompensated by three cardiogenic shocks and a neonatal deep right sylvian stroke. The child died at 24 days of life. This is the first report of a pathogenic stop-loss variant in ENPP1. It is an opportunity to remind clinicians of GACI disease, a rare and severe etiology in neonates with severe hypertension, and possibility of bisphosphonates therapy.

Systemic chemotherapy and surgical cytoreduction for poorly differentiated and signet ring cell adenocarcinomas of the appendix.

BACKGROUND: Poorly differentiated and signet ring cell adenocarcinomas of the appendix represent a subset with aggressive tumor biology and poor outcomes with few studies evaluating the impact of systemic chemotherapy and cytoreductive surgery (CRS). PATIENTS AND METHODS: A retrospective chart review of patients with either poorly differentiated and signet ring cell appendiceal adenocarcinomas was completed from 1992 to 2010. RESULTS: One hundred forty-two patients were identified. Seventy-eight patients with metastatic disease received chemotherapy. Radiographic response was 44%, median progression-free survival (PFS) was 6.9 months, and median overall survival (OS) was 1.7 years. In multivariate analysis, response to chemotherapy [hazard ratio (HR) 0.5; P = 0.02] predicted improved PFS, and complete CRS (HR 0.3; P = 0.004) predicted improved OS. Patients who underwent complete CRS (n = 26) had a median relapse-free survival (RFS) of 1.2 years and a median OS of 4.2 years. In multivariate analysis for this subset, complete cytoreduction score of 0 was significantly correlated with improved RFS (HR 0.07; P = 0.01) and OS (HR 0.02; P = 0.01). CONCLUSIONS: Systemic chemotherapy appears to be a viable treatment option for patients with metastatic poorly differentiated and signet ring cell appendiceal adenocarcinomas. Complete CRS is associated with improved RFS and OS, though part of this benefit likely reflects the selection of good tumor biology.

Clinical insight level predicts successful quit or control attempts during the first three months of outpatient addiction treatment.

INTRODUCTION: Low clinical insight in psychiatry is defined as poor recognition of one's mental illness, including disability to self-evaluate symptom severity. It has been reported as common in addiction and is associated with lower treatment compliance. Longitudinal studies suggest that low clinical insight could be linked to more relapse. However, association with successful quit attempts remains unknown. OBJECTIVE: Our objective was to examine the prospective link between baseline clinical insight level and self-reports of successful attempts to quit / control use during the first 3 months of outpatient addiction treatment. METHODS: Participants were recruited from the ADDICTAQUI cohort at outpatient treatment intake for substance or behavioral addictions. They completed a baseline evaluation using the Addiction Severity Index (ASI), the Mini International Neuropsychiatric Interview (MINI), and the modified Hanil Alcohol Insight Scale (m-HAIS) with a follow-up ASI 3 months later. Data were analyzed using multiple logistic regression and non-parametric tests. RESULTS: Lower clinical insight level at baseline was associated with less successful quit / control attempts during the first 3 months of outpatient treatment compared to a higher clinical insight level, controlling for sociodemographic factors, baseline addiction severity, and comorbidities (n = 54; exp(B) = 0.76; p (FDRcor) = 0.033). CONCLUSION: Poor clinical insight may be a barrier to treatment success, and future studies should examine underlying mechanisms.

Boosting Student Wellbeing Despite a Pandemic: Positive Psychology Interventions and the Impact of Sleep in the United Arab Emirates.

Positive psychology interventions hold great promise as schools around the world look to increase the wellbeing of young people. To reach this aim, a program was developed to generate positive emotions, as well as improve life satisfaction, mental toughness and perceptions of school kindness in 538 expatriate students in Dubai, United Arab Emirates. Starting in September 2019, the program included a range of positive psychology interventions such as gratitude, acts of kindness and mental contrasting as examples. Life satisfaction and mental toughness at mid-year were sustained or grew by the end of the year. Positive affect, emotional wellbeing and social wellbeing increased at post-intervention 1, compared to baseline. However, this improvement reverted to baseline levels at post-intervention 2, when data were collected during the COVID-19 pandemic. Only psychological wellbeing, negative affect, perceptions of control, and school kindness were increased at post-intervention 2. During the lockdown, students moved less, but slept and scrolled more. Those who extended their sleep duration reported greater wellbeing. Boosting wellbeing through the use of positive psychology interventions works - even in a pandemic - and extended sleep duration appears to be a driving factor for this observation.