Rejected

The objective was to describe pain characteristics and treatments used in individuals with varying severity of osteogenesis imperfecta (OI) and investigate pain-associated variables. This work was derived from a multicenter, longitudinal, observational, natural history study of OI conducted at 12 clinical sites of the NIH Rare Diseases Clinical Research Network's Brittle Bone Disorders Consortium. Children and adults with a clinical, biochemical, or molecular diagnosis of OI were enrolled in the study. We did a cross-sectional analysis of chronic pain prevalence, characteristics, and treatments used for pain relief and longitudinal analysis to find the predictors of chronic pain. We included 861 individuals with OI, in 41.8% chronic pain was present, with similar frequency across OI types. Back pain was the most frequent location. Nonsteroidal anti-inflammatory drugs followed by bisphosphonates were the most common treatment used. Participants with chronic pain missed more days from school or work/year and performed worse in all mobility metrics than participants without chronic pain. The variables more significantly associated with chronic pain were age, sex, positive history of rodding surgery, scoliosis, other medical problems, assistive devices, lower standardized height, and higher body mass index. The predictors of chronic pain for all OI types were age, use of a wheelchair, and the number of fractures/year. Chronic pain is prevalent in OI across all OI types, affects mobility, and interferes with participation. Multiple covariates were associated with chronic pain.

Two novel inhibitors of isocitrate dehydrogenase (IDHi), ivosidenib and enasidenib, significantly improve survival for AML patients with an IDH1 or IDH2 mutation, respectively; however, rash has been reported as a toxicity of IDHi. The objective of our study is to determine the incidence, grade, clinical, and histopathologic features of dermatologic adverse events (DAEs) secondary to IDHi. This study is a retrospective analysis of 169 patients who were treated with either ivosidenib or enasidenib as single agent or in combination with induction chemotherapy at Memorial Sloan Kettering Cancer Center from January 1, 2013 to April 1, 2021. DAEs thought to be possibly, probably, or definitely related to IDHi occurred in 55 of 169 patients [0.32, 95 % CI: 0.25 – 0.40]. Of a total 81 DAEs observed, the most common DAE types were inflammatory dermatoses (27 %); cutaneous vascular manifestations (8%); cutaneous infections (7%); and pruritus (2%). Notably, 50% of infections and 15.5% of rashes were high grade. Knowledge of these findings is critical to optimize the treatment and quality of life of patients with AML on IDHi.

Non-steroidal anti-inflammatory drug (NSAID) use in elite sport is high, with football being no exception. Increased awareness of significant adverse drug reactions from published research and retired players commentary in the media have made the topic mainstream. Despite this increased awareness, usage rates show no sign of significantly reducing. Footballers, like all elite athletes are focused on maximising their performance and potential – even at the expense of their long-term health. An educational intervention prior to the 2010 FIFA Men's World Cup aimed at reducing rates was ineffective, suggesting that education alone is not the answer. Our author group propose a "safer use" rather than "no use" of NSAIDs in football. A 'Keeping SCORE' approach is suggested, designed as a prescribing aid. The approach guides medical staff towards focusing on Safety checks, Clinical indication/judgement, Open dialogue, Recording, and Evaluation.

Microneedle (MN) patches are highly efficient and versatile tools for transdermal drug administration, in particular for pain-free, self-medication and rapid local applications. Diffraction ultraviolet (UV) light lithography offers an advanced method in fabricating poly(ethylene glycol)-based MNs with different shapes, by changing both the UV-light exposure time and photomask design. The exposure time interval is limited at obtaining conical structures with aspect ratio < 1:3, otherwise MNs exhibit reduced fracture load and poor indentation ability, not suitable for practical application. Therefore, this work is focused on a systematic analysis of the MN's base shapes effects on the structural characteristics, skin penetration and drug delivery. Analyzing four different base shapes (circle, triangle, square and star), it has been found that the number of vertices in the polygon base heavily affects these properties. The star-like MNs reveal the most efficient skin penetration ability (equal to 40 % of -their length), due to the edges action on the skin during the perforation. Furthermore, the quantification of the drug delivered by the MNs through ex-vivo porcine skin shows that the amounts of small molecules released over 24 h by star-like MNs coated by local anesthetic (Lidocaine) and an anti-inflammatory (Diclofenac epolamine) drugs are 1.5× and 2× higher than the circular-MNs, respectively.

Neuropathic arthropathy (NA) is a long-term progressive disorder that causes joint destruction in the existence of a neurologic deficit. Minor injuries and fractures are commonly overlooked until the visible joint deterioration becomes persistent. Syringomyelia is one of the important causes of NA. The appearance of clinical signs in syringomyelia is caused by longitudinal cysts formed in the cervical and cervicothoracic regions of the spinal cord. Depending on the existence of the underlying disorder, the number and localization of the syrinxes, a range of symptoms, involving pain, sensation deficit, loss of motor function, and deep tendon reflex abnormality, emerge. The case is here described of a 68-year-old female patient with shoulder NA following syringomyelia, who partially responded to the rehabilitation program. Furthermore, the available case reports were comprehensively reviewed on Web of Science, Scopus, and PubMed/Medline. Furthermore, the available case reports were comprehensively evaluated on Web of Science, Scopus, and PubMed/Medline. Thus, we aimed to present the demographic characteristics, symptoms, physical examination signs, treatment, and follow-up parameters of syringomyelia-related shoulder NA cases.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that originate from the gastrointestinal tract wall. Approximately 20-30 % of GISTs originate from the small intestine. GISTs of the small intestine generally present with a palpable mass, distention, and abdominal pain and may exhibit acute abdomen at the onset. Herein, we describe a rare case of a pedunculated GIST of the small intestine complicated by torsion.

The present case of a patient with several co-morbidities undergoing complex vitrectomy under peribulbar block and sedation with Target Controlled Infusion (TCI of propofol and dexmedetomidine with EEG and Analgesia Nociception Index (ANI) monitoring illustrates the benefits of multimodal monitoring to differentiate the effect of hypnotic and antinociceptive drugs.It is highlighted the delta-alpha electroencephalographic pattern showing adequate sedation, the beta arousal pattern in the EEG concommitant to decrease in the ANI translating insufficient anti-nociception.

Upon exposure to internal or external stressors, ribosomes stand sentinel via modulation of ribosome assembly and protein translation. Ribosome-dependent cellular dysfunctions have been associated with pathophysiological processes during inflammation and tumorigenesis. In the present study, ribosome biogenesis was assessed to determine its effects on tumor chemokines, potentially contributing to cancer cell malignant features. In particular, ribosome biogenesis inhibition by antibiotic actinomycin D (ActD) enhanced the expression of chemokines in intestinal cancer cells under endoplasmic reticulum stress that governs multiple pro-tumoral reprogramming. Mechanistically, ribosome biogenesis inhibition superinduced proinflammatory chemokines via transcriptional and post-transcriptional regulation. Moreover, ribosomal stress-responsive p53 and its target macrophage inhibitory cytokine 1 (MIC-1) mediated chemokine superinduction by activating TGF-β-activated kinase 1 (TAK-1) and nuclear factor-kappa B (NF-κB) in intestinal cancer cells. Cancer cell-based regulation of chemokine induction via MIC-1 signaling was verified using clinical transcriptome datasets. Clinical tumor tissue-derived MIC-1 was a positive regulator of chemokines and genes involved in the ribosome biogenesis pathway, supporting the in vitro assessments. Moreover, MIC-1-correlated chemokine expressions predicted poor prognoses in patients with colorectal cancer. Ribosome-based chemokine regulation via MIC-1 signaling would provide novel insights into translational interventions against malignant inflammatory insults.

we sought to explore the efficacy of ketamine in a patient on extracorporeal membrane oxygenation (ECMO) receiving ketamine for sedation by investigating the utility of plasma ketamine concentrations. retrospective chart review of one critically ill patient on ECMO This was a descriptive review of serial plasma ketamine concentrations in an ECMO patient. Although no reference plasma concentrations exist in ECMO patients, ketamine levels appeared to be lower than those seen in surgical patients not on ECMO. At this point, no reference plasma concentrations exist for ketamine in ECMO patients, further research may help understand the effects of ECMO on ketamine disposition and that lower ketamine concentrations may be used for effective analgesia or sedation.

Social determinants of health (SDOH) influence inequities in systemic lupus erythematosus (SLE). While these inequities contribute to overall disease experience, there is little consensus guiding our understanding of the psychological implications of SDOH in SLE. Given the paucity of evidence in this area, the aim of this scoping review was to systematically assess the volume and features of available research literature on associations of SDOH with depression in SLE over the past 20 years, from 1 January 2000 to 16 November 2021. We developed a search strategy for PubMed and EMBASE that included keywords for depression and lupus. After screening 2188 articles, we identified 22 original articles that met our inclusion criteria. At least one SDOH was associated with depression in two of the six studies with unadjusted estimates and 13 of the 16 studies with adjusted estimates. Results provide consistent but sparse evidence that SDOH are associated with depression in SLE. Additionally, depression epidemiology in SLE may differ from the general population such that depression risk is more similar across genders and racial/ethnic groups. More work is needed to identify the SDOH that have the greatest impact on depression and mental health among SLE patients, as well as how and when to intervene.