Vogelneergaard2686

Thus, pain was helping them to normalize their end-of-life experiences and ease the terminal stage of their illness.Duchenne muscular dystrophy (DMD) is an intractable genetic disease associated with progressive skeletal muscle weakness and degeneration. Recently, it was reported that intraperitoneal injections of ketone bodies partially ameliorated muscular dystrophy by increasing satellite cell (SC) proliferation. Here, we evaluated whether a ketogenic diet (KD) with medium-chain triglycerides (MCT-KD) could alter genetically mutated DMD in model rats. We found that the MCT-KD significantly increased muscle strength and fiber diameter in these rats. The MCT-KD significantly suppressed the key features of DMD, namely, muscle necrosis, inflammation, and subsequent fibrosis. Immunocytochemical analysis revealed that the MCT-KD promoted the proliferation of muscle SCs, suggesting enhanced muscle regeneration. The muscle strength of DMD model rats fed with MCT-KD was significantly improved even at the age of 9 months. Our findings suggested that the MCT-KD ameliorates muscular dystrophy by inhibiting myonecrosis and promoting the proliferation of muscle SCs. As far as we can ascertain, this is the first study to apply a functional diet as therapy for DMD in experimental animals. Further studies are needed to elucidate the underlying mechanisms of the MCT-KD-induced improvement of DMD.Unknown chemical releases constitute a large portion of the rapid response situations to which the U.S. Environmental Protection Agency (U.S. EPA) is called upon to respond. Workflows used to address unknown chemical releases currently involve screening for a large array of known compounds using many different targeted methods. When matches are not found, expert analytical chemistry knowledge is used to propose possible candidates from the available data, which generally includes low-resolution mass spectra and situational clues such as the location of the release, nearby industrial operations, and other field-reported facts. The past decade has witnessed dramatic improvements in capabilities for identifying unknown compounds using high-resolution mass spectrometry (HRMS) and non-targeted analysis (NTA) approaches. Complementary developments in cheminformatics tools have further enabled an increase in NTA throughput and identification confidence. Together with the expanding availability of HRMS instrumentation in monitoring laboratories, these advancements make NTA highly relevant to rapid response scenarios. In this article, we introduce the concept of NTA as it relates to rapid response needs and describe how it can be applied to address unknown chemical releases. We advocate for the consideration of HRMS-based NTA approaches to support future rapid response scenarios. This article is protected by copyright. All rights reserved.

To assess the relationship between neonatal brain development and injury with early motor outcomes in infants with critical congenital heart disease (CCHD).

Neonatal brain magnetic resonance imaging was performed after open-heart surgery with cardiopulmonary bypass. Cortical grey matter (CGM), unmyelinated white matter, and cerebellar volumes, as well as white matter motor tract fractional anisotropy and mean diffusivity were assessed. White matter injury (WMI) and arterial ischaemic stroke (AIS) with corticospinal tract (CST) involvement were scored. Associations with motor outcomes at 3, 9, and 18months were corrected for repeated cardiac surgery.

Fifty-one infants (31 males, 20 females) were included prospectively. Median age at neonatal surgery and postoperative brain magnetic resonance imaging was 7 days (interquartile range [IQR] 5-11d) and 15 days (IQR 12-21d) respectively. Smaller CGM and cerebellar volumes were associated with lower fine motor scores at 9 months (CGM regression coefficient=0.51, 95% confidence interval [CI]=0.15-0.86; cerebellum regression coefficient=3.08, 95% CI=1.07-5.09) and 18 months (cerebellum regression coefficient=2.08, 95% CI=0.47-5.12). The fractional anisotropy and mean diffusivity of white matter motor tracts were not related with motor scores. WMI was related to lower gross motor scores at 9 months (mean difference -0.8SD, 95% CI=-1.5 to -0.2). AIS with CST involvement increased the risk of gross motor problems and muscle tone abnormalities. Cerebral palsy (n=3) was preceded by severe ischaemic brain injury.

Neonatal brain development and injury are associated with fewer favourable early motor outcomes in infants with CCHD.

Neonatal brain development and injury are associated with fewer favourable early motor outcomes in infants with CCHD.

Onychophagia is a common disorder affecting 20% to 30% of the general population. It is defined as habitual nail biting and can cause various changes in the nail units. However, to date, there has been a paucity of data focusing on nail deformities related to onychophagia. This study was performed to investigate the clinical characteristics of onychophagia in Korea.

This study included 53 patients with onychophagia who visited the Pusan National University Hospital (Busan and Yangsan) over a 10-year period (2011-2020). We retrospectively reviewed medical records and clinical and dermoscopic photographs.

All 10 fingernails were affected in 37.7% of the patients. The left thumbnail was the most predominantly affected site (81.1%). Clinical findings showed that short nails with ragged distal borders were the most common presentation (100.0%), followed by generalized or patchy rough areas (50.9%), linear and pinpoint hemorrhage (32.1%), longitudinal melanonychia (30.2%), transverse groove (28.3%), brittleness (28.3%), macrolunula (24.5%), washboard nail (13.2%), and pterygium (3.8%). Of the patients, 88.7% had periungual complications, such as periungual exfoliation (77.4%), absent or ragged cuticle (52.8%), hyponychial hyperkeratosis (37.7%), and paronychia (15.1%).

Although onychophagia is a common disorder, its clinical characteristics have not been reported in the literature. The results of this study may be helpful in managing patients with onychophagia.

Although onychophagia is a common disorder, its clinical characteristics have not been reported in the literature. The results of this study may be helpful in managing patients with onychophagia.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are treated with trastuzumab-based neoadjuvant therapy (NAT); some patients with residual disease post-NAT show loss of HER2 amplification and has been inconsistently associated with oncologic outcomes.

We queried our multi-institutional cancer registry for women with HER2-positive breast cancer undergoing NAT from 2011 to 2018. Clinicopathologic, treatment-related, and outcomes data were collected. Kaplan-Meier and Cox proportional hazards analysis were used to evaluate oncologic outcomes.

A total of 348 patients were identified; 166 (48%) had a pathologic complete response. Of the 182 patients with residual disease, 87 (48%) were HER2-positive, 34 (19%) were HER2-negative, and 61 (33%) were HER2-unknown, with a median follow-up of 44 months. There were no factors associated with HER2 loss apart from age. On Kaplan-Meier analysis, estimated 5-year recurrence-free survival (RFS) and overall survival (OS) for patients with HER2-positive residual disease was 81% and 92%, respectively, and 74% (log rank p = 0.75) and 81% (p = 0.35) in patients with HER2-negative residual disease.

The loss of HER2-positivity following NAT is not associated with worse 5-year RFS or OS. We do not recommend retesting HER2 status following NAT for the purpose of clinical management; these patients should complete targeted adjuvant therapy.

The loss of HER2-positivity following NAT is not associated with worse 5-year RFS or OS. We do not recommend retesting HER2 status following NAT for the purpose of clinical management; these patients should complete targeted adjuvant therapy.Regulatory agencies are increasingly considering real-world evidence (RWE) to support label expansions of approved medicines. We conducted a comparative effectiveness study to emulate a proposed randomized trial of romiplostim vs. standard-of-care (SOC) therapy among patients with recently diagnosed (≤12 months) immune thrombocytopenia (ITP), that could support expansion of the romiplostim label. We discuss challenges that we encountered and solutions that were developed to address those challenges. Study size was a primary concern, particularly for romiplostim initiators, given the rarity of ITP and the stringent trial eligibility criteria. For this reason, we leveraged multiple data sources (Nordic Country Patient Registry for Romiplostim; chart review study of romiplostim initiators in Europe; Flatiron Health EMR linked with MarketScan claims). Additionally, unlike the strictly controlled clinical trial setting, platelet counts were not measured at regular intervals in the observational data sources, and therefore the end point of durable platelet response often used in trials could not be reliably measured. Instead, the median platelet count was chosen as the primary end point. Ultimately, while we observed a slightly higher median platelet count in the romiplostim group vs. SOC, precision was limited because of small study size (median difference was 11 × 109 /L (95% CI -59, 81)). We underscore the importance of conducting comprehensive feasibility assessments to identify fit-for-purpose data sources with sufficient sample size, data elements, and follow-up. Beyond technical challenges, we also discuss approaches to increase the credibility of RWE, including systematic incorporation of clinical expertise into study design decisions, and separation between decision makers and the data.

Organ transplant recipients (OTRs) are at high risk of developing skin cancer and are therefore advised to protect their skin against ultraviolet radiation from the sun. Specialized OTR clinics with dermatological follow-up may improve sun habits among OTRs. In this study, we compared self-reported sun exposure and sun protection behaviour between OTRs and non-transplant patients (non-TPs) and between OTRs with and without special dermatological follow-up.

Patients from Sahlgrenska University Hospital, Gothenburg, Sweden, completed a sun exposure questionnaire. Between 2011 and 2015, 282 OTRs transplanted in the period 1976-2014 and 414 non-TPs were recruited among dermatological outpatients. Participants were stratified into five groups by their status as OTRs or non-TPs and by attendance to dermatological follow-up.

More non-TPs than OTRs reported one or more sunburns in the past year, 46% vs. 20%, P<.0001). More OTRs with than OTRs without dermatological follow-up reported frequent use of sunscreens (63% vs 44%, P=.006). More OTRs with follow-up used one or more sun protection measure such as covering clothes, than other OTRs (54% vs 34%, P=.016).

In this study, OTRs reported less sun exposure than non-TPs. Specialized dermatological follow-up seems to improve sun protection behaviour among OTRs. click here We suggest that specialized OTR clinics should be more broadly implemented.

In this study, OTRs reported less sun exposure than non-TPs. Specialized dermatological follow-up seems to improve sun protection behaviour among OTRs. We suggest that specialized OTR clinics should be more broadly implemented.