Rejected

Chronic pain is often associated with functional limitations that have a huge impact on patients' lives. However, despite being relatively common, chronic musculoskeletal pain is still viewed by some as a symptom of another disease rather than its own condition, and is therefore poorly addressed. This is compounded by other challenges in the field, including education gaps for both healthcare professionals and patients, a lack of universal and comprehensive assessment tools, poor societal perceptions of chronic pain, and the current stigma around the use of opioids. Here, we review the current chronic musculoskeletal pain management landscape in the United States and offer professional insight into emerging methods that can be used to improve patient outcomes, in particular, the achievement of meaningful functional goals. This perspective incorporates our combined multidisciplinary (psychiatry, psychology, nursing, physical therapy, and general medicine) experience and insights. We believe that chronic pain is a multifactorial experience and treatment requires an integrated, multidisciplinary approach from a range of healthcare providers. For the best patient outcomes, this team should work together to assess and treat the patient as a whole, addressing their pain and also providing education, empowerment, and support to enable patients to set and achieve meaningful functional goals that will provide real improvement in their quality of life. We believe that the healthcare community should elevate the conversation around chronic musculoskeletal pain management beyond that of just pain, to encompass the meaningful benefits that improvement in functional outcomes brings to patients.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory condition marked by pruritus and traditionally treated with topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI). Crisaborole 2% ointment (a topical phosphodiesterase-4 inhibitor) is a newer topical agent for the treatment of AD. Crisaborole is indicated for treating mild-to-moderate AD and evidence from phase 3 and phase 4 trials show that crisaborole is an effective agent with a well-tolerated side effect profile for children >2 years of age. The most common side effects are pain and paresthesia at the application site. Treatments with tolerable safety profiles such as crisaborole may provide an alternative to patients with TCS phobia. The role of crisaborole in AD therapy may become clearer as multiple phase 4 trials are currently underway and their results are poised to answer more questions, including its safety profile for patients as young as 3 months of age, potential use as a steroid-sparing agent, and direct comparisons to TCS and TCI, which are the current mainstay treatments of mild-to-moderate AD.

Osteoarthritis (OA) is one of the major causes of chronic pain in dogs. However, the pathogenesis of OA has not been fully understood in dogs. The objective of this study was to comprehensively investigate the mRNA expression levels of proinflammatory cytokines, inflammatory mediators, nerve growth factor and its receptor, and matrix metalloproteinases in the synovium of dogs with spontaneous OA as well as to elucidate their relationships with the severity of synovitis. Dogs that were diagnosed with stifle OA on the basis of radiographic findings were included, and the degree of synovitis was observed using stifle arthroscopy. The dogs were assigned to two different groups depending on their synovitis scores: the low-grade group (score of 1 or 2; n = 8) and high-grade group (score of 3 to 5; n = 18). The dogs showing no evidence of orthopedic disease were included in the control group (n = 6). Synovial tissue samples were collected from the sites at which synovitis scores were assessed using arthroscopy. Total RNA was extracted from the collected synovial tissue, and cDNA was synthesized. Subsequently, RT-qPCR were performed using canine-specific primer sets for IL1B, IL6, CXCL8, TNF, TGFB1, PTGS2, PTGES, MMP3, MMP13, NGF, NTRK1, and PTGER4. Expression levels of IL1B, IL6, CXCL8, and MMP13 were significantly higher in the high-grade group than in the control group. In addition, expression levels of IL1B, CXCL8, TNF, and PTGS2 were significantly higher in the high-grade group than in the low-grade group. Expression levels of IL1B, IL6, CXCL8, TNF, PTGS2, and PTGER4 showed significant positive correlation with synovitis score. In conclusion, all mRNA expression levels in the synovial membrane varied according to the degree of synovitis in dogs with spontaneous OA. Thus, this study may partially elucidate the pathogenesis of synovitis in dogs with spontaneous OA.

Tuberculosis is an airborne multisystemic disease which primarily infects the lungs. Isolated tuberculous arthritis is rare. We present a case of a 41-year-old woman with a known case of lupus nephritis class IV who complained of pain and swelling over her left ankle joint for several months. She was treated for rheumatoid arthritis and was started with immunosuppressive agents. However, she did not improve with treatment and was later diagnosed with tuberculous arthritis based on a molecular study from joint aspiration. She was started on antituberculosis medication and showed improvement. We highlight the challenges in reaching the diagnosis and the importance of including tuberculous arthritis in differential diagnoses in cases with persistent ankle swelling.

The purpose of this translational review was to provide evidence to support the natural evolution of the nomenclature of neuromodulatory and neuroablative radiofrequency lesions for pain management from lesions of individualized components of the linear dorsal afferent pathway to "Dorsal Root Entry Zone Complex (DREZC) lesions." Literature review was performed to collate anatomic and procedural data and correlate these data to clinical outcomes. There is ample evidence that the individual components of the DREZC (the dorsal rami and its branches, the dorsal root ganglia, the dorsal rootlets, and the dorsal root entry zone) vary dramatically between vertebral levels and individual patients. Procedurally, fluoroscopy, the most commonly utilized technology is a 2-dimensional x-ray-based technology without the ability to accurately locate any one component of the DREZC dorsal afferent pathway, which results in clinical inaccuracies when naming each lesion. Despite the inherent anatomic variability and these procedural limitations, the expected poor clinical outcomes that might follow such nomenclature inaccuracies have not been shown to be prominent, likely because these are all lesions of the same anatomically linear sensory pathway, the DREZC, whereby a lesion in any one part of the pathway would be expected to interrupt sensory transmission of pain to all subsequent more proximal segments. Given that the common clinically available tools (fluoroscopy) are inaccurate to localize each component of the DREZC, it would be inappropriate to continue to erroneously refer to these lesions as lesions of individual components, when the more accurate "DREZC lesions" designation can be utilized. Hence, to avoid inaccuracies in nomenclature and until more accurate imaging technology is commonly utilized, the evidence herein supports the proposed change to this more sensitive and inclusive nomenclature, "DREZC lesions."

Sciatic nerve injury due to intramuscular injection (SNIII) is still a health problem. This study aimed to determine whether there is a correlation between neuropathic pain and electrodiagnostic findings in SNIII.

Few studies have examined health-related quality of life (HRQoL) among people living with HIV (PLWHIV) in Eastern Europe and Central Asia. We conducted a cross-sectional survey of 180 PLWHIV aged 18 years+ in Armenia who were on cART and used the 36-Item Short-Form Health Survey to assess HRQoL. The highest HRQoL domain score was 85.3 (SD 24.7) for physical functioning, followed by 82.1 (SD 25.0) for pain, 77.9 (SD 24.2) for social functioning, 76.4 (SD 39.6) for emotional role-functioning, 71.1 (SD 39.7) for physical role-functioning, and 64.0 (SD 20.3) for energy/fatigue, 63.7 (SD 22.7) for emotional well-being and 63.4 for general health 63.4 (SD 21.2). In the physical domain, chronic comorbidities and low emotional support were associated with worse physical functioning, physical role-functioning, general health and pain scores ( < 0.05). Unemployment and hepatitis C coinfection were associated with worse physical role functioning and pain scores ( < 0.01). As for mental HRQoL, we found that unemployment, chronic comorbidities, and lower emotional support were associated with poorer emotional well-being, energy, and emotional role-functioning scores ( < 0.05). These findings suggest that improved social support, employment opportunities, mental health services and integrated care for noncommunicable comorbidities may improve HRQoL in Armenia and similar settings.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by recurrent eczematous lesions and intense pruritus. AD patients are known to face a considerable disease burden, including physical and emotional limitations. There is still limited knowledge about daily implications in education and occupation. We describe disease social stigmatization by measuring bullying and self-isolation in students and professional discrimination in workers. Overall loss of productivity, either at school and at the workplace, was quantified as the sum of absenteeism (number of days AD sick leave) and presenteeism (number of days with decreased focus and functionality).

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children's hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Insect stings and the resulting itch are a ubiquitous problem. Stings by members of the insect order Hymenoptera, which includes sawflies, wasps, bees and ants, and especially by bees and wasps are extremely common, with 56-94% of the population being stung at least once in their lifetime. The complex process of venom activity and inflammation causes local reactions with pain and pruritus, sometimes anaphylactic reactions and more seldomly, as in case of numerous stings, systemic intoxication. We reviewed the literature regarding itch experienced after Hymenoptera stings, but found no study that placed a specific focus on this topic. Hymenoptera venoms are composed of many biologically active substances, including peptide toxins and proteinaceous toxins. Peptide toxins from bee venom cause cell lysis and ion channel modulation in the peripheral and central nervous systems, while toxins from wasp venom induce mast cell degranulation and chemotaxis of polymorphonuclear leukocytes in the skin. The proteinaceous toxins cause a disruption of the cell membranes and necrotic cell death, degradation of hyaluronan (an extracellular matrix glycosaminoglycan), increased vascular permeability, hemolysis, as well as activated platelet aggregation. Mediators which could be directly involved in the venom-induced pruritus include histamine and tryptase released from mast cells, interleukin-4 and interleukin-13 from Th2 lymphocytes, as well as leukotriene C4. We postulate that a pruriceptive itch is induced due to the pharmacological properties of Hymenoptera venoms.