Growth hormone (GH) is crucial for childhood growth and body composition. In pediatric GH deficiency (pGHD), the pituitary gland fails to produce sufficient GH, which affects linear growth in childhood. pGHD is conventionally treated with daily recombinant human GH (rhGH); however, because GH therapy lasts throughout childhood, adherence to daily rhGH treatment can be low, resulting in suboptimal effectiveness. Somatrogon is a long-acting GH analog designed to address the challenges associated with daily GH therapy for pGHD. Somatrogon administered once per week is a potential alternative to daily GH therapy. The use of somatrogon is supported by phase II and III clinical trials demonstrating that once-weekly injections are noninferior to once-daily somatropin injections in terms of efficacy, safety, and tolerability and have the advantage of reduced treatment burden. This review summarizes the clinical trials of somatrogon and discusses the therapeutic profile and effects of treating pGHD with reduced injection frequency.

Growth hormone (GH) is crucial for childhood growth and body composition. In pediatric GH deficiency (pGHD), the pituitary gland fails to produce sufficient GH, which affects linear growth in childhood. pGHD is conventionally treated with daily recombinant human GH (rhGH); however, because GH therapy lasts throughout childhood, adherence to daily rhGH treatment can be low, resulting in suboptimal effectiveness. Somatrogon is a long-acting GH analog designed to address the challenges associated with daily GH therapy for pGHD. Somatrogon administered once per week is a potential alternative to daily GH therapy. The use of somatrogon is supported by phase II and III clinical trials demonstrating that once-weekly injections are noninferior to once-daily somatropin injections in terms of efficacy, safety, and tolerability and have the advantage of reduced treatment burden. This review summarizes the clinical trials of somatrogon and discusses the therapeutic profile and effects of treating pGHD with reduced injection frequency.

Growth hormone (GH) is crucial for childhood growth and body composition. In pediatric GH deficiency (pGHD), the pituitary gland fails to produce sufficient GH, which affects linear growth in childhood. pGHD is conventionally treated with daily recombinant human GH (rhGH); however, because GH therapy lasts throughout childhood, adherence to daily rhGH treatment can be low, resulting in suboptimal effectiveness. Somatrogon is a long-acting GH analog designed to address the challenges associated with daily GH therapy for pGHD. Somatrogon administered once per week is a potential alternative to daily GH therapy. The use of somatrogon is supported by phase II and III clinical trials demonstrating that once-weekly injections are noninferior to once-daily somatropin injections in terms of efficacy, safety, and tolerability and have the advantage of reduced treatment burden. This review summarizes the clinical trials of somatrogon and discusses the therapeutic profile and effects of treating pGHD with reduced injection frequency.

Objectives: Pustular psoriasis (PP) is one of the most severe and chronic skin conditions. Its treatment is difficult, and measurements of its severity are highly dependent on clinicians’ experience. Pustules and brown spots are the main efflorescences of the disease and directly correlate with its activity. We propose an automated deep learning model (DLM) to quantify lesions in terms of count and surface percentage from patient photographs. Methods: In this retrospective study, two dermatologists and a student labeled 151 photographs of PP patients for pustules and brown spots. The DLM was trained and validated with 121 photographs, keeping 30 photographs as a test set to assess the DLM performance on unseen data. We also evaluated our DLM on 213 unstandardized, out-of-distribution photographs of various pustular disorders (referred to as the pustular set), which were ranked from 0 (no disease) to 4 (very severe) by one dermatologist for disease severity. The agreement between the DLM predictions and experts’ labels was evaluated with the intraclass correlation coefficient (ICC) for the test set and Spearman correlation (SC) coefficient for the pustular set. Results: On the test set, the DLM achieved an ICC of 0.97 (95% confidence interval [CI], 0.97–0.98) for count and 0.93 (95% CI, 0.92–0.94) for surface percentage. On the pustular set, the DLM reached a SC coefficient of 0.66 (95% CI, 0.60–0.74) for count and 0.80 (95% CI, 0.75–0.83) for surface percentage. Conclusions The proposed method quantifies efflorescences from PP photographs reliably and automatically, enabling a precise and objective evaluation of disease activity.

Boerhaave syndrome (BS) is a spontaneous esophageal perforation which carries high mortality. Surgical treatment is well established, but the development of interventional endoscopy has proposed new therapies. We expose our experience in a Gastrointestinal and Endoscopy Unit. With a retrospective, observational, open-label, single center, consecutive case series. All patients diagnosed with BS who were managed in our center were included. Treated conservatively, endoscopically or surgically, according to their clinical condition and lesion presentation. Fourteen patients were included. Ten were treated with primary surgery. One conservatively. In total, 7/14 patients required an endoscopic treatment. All required metallic stents deployment, 3 cases over-the-scope-clips concomitantly and one case a novel technique an internal drain. 6/7 cases endoscopically treated achieved complete esophageal healing. In conclusion, endoscopy is an useful tool at all stages BS management: difficult diagnosis, primary treatment in selected patients and as salvage when surgery fails. With mortality rates and outcomes comparables to surgery.
Diagnosis ; Endoscopy* ; Esophageal Perforation ; Humans ; Minimally Invasive Surgical Procedures ; Mortality ; Retrospective Studies ; Stents ; Surgical Instruments

Recent experience with pandemic influenza A(H1N1)pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI) cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition.All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization’s SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources.Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9) virus infections and seasonal influenza prevention and control.

The aim was to describe out-of-hospital cardiac arrest (OHCA) occurring in the workplace of a large emergency network, and compare the evolution of their management in the last 15 years. A retrospective study based on data from the Northern Alps Emergency Network compared characteristics of OHCA between cases in and out the workplace, and between cases occurring from January 2004 to December 2010 and from January 2011 to December 2017. Among the 15,320 OHCA cases included, 320 occurred in the workplace (2.1%). They were more often in younger men, and happened more frequently in an area with access to public defibrillation, had more often a shockable rhythm, had a cardiopulmonary resuscitation started by a bystander more frequently, and had a better outcome. Cardiopulmonary resuscitation started by a bystander was the only chain of survival link that improved for cases occurring after December 2010. Workplace OHCA seems to be managed more effectively than others; however, only a slight survival improvement was observed, suggesting that progress is still needed.

Articular cartilage, which is mainly composed of collagen II, enables smooth skeletal movement. Degeneration of collagen II can be caused by various events, such as injury, but degeneration especially increases over the course of normal aging. Unfortunately, the body does not fully repair itself from this type of degeneration, resulting in impaired movement. Microfracture, an articular cartilage repair surgical technique, has been commonly used in the clinic to induce the repair of tissue at damage sites. Mesenchymal stem cells (MSC) have also been used as cell therapy to repair degenerated cartilage. However, the therapeutic outcomes of all these techniques vary in different patients depending on their age, health, lesion size and the extent of damage to the cartilage. The repairing tissues either form fibrocartilage or go into a hypertrophic stage, both of which do not reproduce the equivalent functionality of endogenous hyaline cartilage. One of the reasons for this is inefficient chondrogenesis by endogenous and exogenous MSC. Drugs that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone, or combined with other techniques to greatly assist the therapeutic outcomes. The recent development of human induced pluripotent stem cell (iPSCs), which are able to self-renew and differentiate into multiple cell types, provides a potentially valuable cell resource for drug screening in a "more relevant" cell type. Here we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis.
Cell Differentiation ; drug effects ; Chondrocytes ; cytology ; drug effects ; metabolism ; Chondrogenesis ; drug effects ; Drug Evaluation, Preclinical ; methods ; Genes, Reporter ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; drug effects ; metabolism ; Keratinocytes ; cytology ; drug effects ; metabolism ; Luciferases ; genetics ; Peptides ; chemical synthesis ; metabolism ; Reproducibility of Results ; Small Molecule Libraries ; pharmacology

Background: and Purpose The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. Methods: In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. Results: The model results yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. Conclusions EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

Background: and Purpose Data on safety and efficacy of intra-arterial (IA) fibrinolytics as adjunct to mechanical thrombectomy (MT) are sparse. Methods: INtra-arterial FIbriNolytics In ThrombectomY (INFINITY) is a retrospective multi-center observational registry of consecutive patients with anterior circulation large-vessel occlusion ischemic stroke treated with MT and adjunctive administration of IA fibrinolytics (alteplase [tissue plasminogen activator, tPA] or urokinase [UK]) at 10 European centers. Primary outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the European Cooperative Acute Stroke Study II definition. Secondary outcomes were mortality and modified Rankin Scale (mRS) scores at 3 months. Results: Of 5,612 patients screened, 311 (median age, 74 years; 44.1% female) received additional IA after or during MT (194 MT+IA tPA, 117 MT+IA UK). IA fibrinolytics were mostly administered for rescue of thrombolysis in cerebral infarction (TICI) 0-2b after MT (80.4%, 250/311). sICH occurred in 27 of 308 patients (8.8%), with an increased risk in patients with initial TICI0/1 (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1 to 5.0 per TICI grade decrease) or in those with intracranial internal carotid artery occlusions (aOR, 3.7; 95% CI, 1.2 to 12.5). In patients with attempted rescue of TICI0-2b and available angiographic follow-up, 116 of 228 patients (50.9%) showed any angiographic reperfusion improvement after IA fibrinolytics, which was associated with mRS ≤2 (aOR, 3.1; 95% CI, 1.4 to 6.9). Conclusions Administration of IA fibrinolytics as adjunct to MT is performed rarely, but can improve reperfusion, which is associated with better outcomes. Despite a selection bias, an increased risk of sICH seems possible, which underlines the importance of careful patient selection.