Rejected

The immunomodulatory potential and low incidence of severe side effects of high-dose intravenous immunoglobulin (IVIg) treatment led to its successful application in a variety of dermatological autoimmune diseases over the last two decades. IVIg is usually administered at a dose of 2 g per kg body weight distributed over 2-5 days every 4 weeks. They are most commonly used as a second- or third-line treatment in dermatological autoimmune disease (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, dermatomyositis, systemic vasculitis, and systemic lupus erythematosus). However, first-line treatment may be warranted in special circumstances like concomitant malignancy, a foudroyant clinical course, and contraindications against alternative treatments. Furthermore, IVIg can be considered first line in scleromyxedema. Production of IVIg for medical use is strictly regulated to ensure a low risk of pathogen transmission and comparable quality of individual batches. More common side effects include nausea, headache, fatigue, and febrile infusion reactions. Serious side effects are rare and include thrombosis and embolism, pulmonary edema, renal failure, aseptic meningitis, and severe anaphylactic reactions. Regarding the mechanism of action, one can discriminate between functions of the Fcγ region and the F(ab)2 region and their effects on a cellular level. These functions are not mutually exclusive, and more than one pathway may contribute to the beneficial effects. Here, we present a historical background, details on manufacturing, hypotheses on the mechanisms of action, information on the clinical application in the abovementioned conditions, and a brief outlook on future directions of IVIg treatment in dermatology.

Peripheral neuropathy is the most common reaction to toxic chemical substances in the nervous system. Toxic neuropathies are often misdiagnosed because there are no easily available specific or biologic tests for the diagnosis. Guillain-Barre syndrome is the most common cause of acute flaccid paralysis in children and adolescents. Clinical signs of the disease are often at the beginning of the distal symmetric weakness and areflexia progresses rapidly. Although capsaicin is widely used in the treatment of so many diseases, especially of neuropathic pain, cancer and osteoarthritis, it is known to be toxic in many systems such as the eye, skin, respiratory, and circulatory systems. Although there is inadequate information about its long-term effects, it has also been reported that in large quantities there is increased risk of toxicity and prolonged exposure can lead to death. In our case, we present acute polyneuropathy mimicking Guillain-Barre syndrome after exposure to pepper spray because it is noteworthy and interesting.

To assess the outcome of conservative treatment for chronic exertional compartment syndrome (CECS) as it relates to the reduction in surgical fasciotomy and return to active duty in a military population.

Back pain, including low back pain and neck pain, is the leading cause of disability worldwide. This type of pain is challenging to treat, since it presents both a nociceptive and a neuropathic component. The latter also contributes to the evolution of pain toward chronification. Treatment selection should therefore consider the ability to prevent this event. Tapentadol is characterized by a unique and innovative peculiar mechanism of action that makes it the first representative of a new class of central strong analgesics referred to as MOR-NRI. This molecule acts both on the nociceptive and neuropathic components of pain, and it can therefore be effective in the treatment of a mixed pain condition such as back pain. This narrative review discusses the rationale for the use of tapentadol in both low back pain and neck pain and presents available clinical data. Overall, data show that tapentadol prolonged release is a well-grounded treatment for chronic back pain, sustained by a strong mechanistic rationale and robust evidence. Given also the availability of long-term efficacy and safety data, we believe that this molecule should be considered as an elective therapy for chronic back pain.

Polyarteritis nodosa (PAN) is a form of necrotizing vasculitis affecting medium or small blood vessels with multiorgan involvement. Although myalgia is a clinical feature of PAN, severe disabling myalgia as the initial presentation is rarely noted.

The dextran sulfate sodium (DSS) model of colitis is a common animal model of inflammatory bowel disease that causes pain and distress. In this study, we aimed to determine whether fluid supplementation can be used as a welfare-based intervention to minimize animal suffering. C57Bl/6 females undergoing acute colitis by administration of 3% DSS in drinking water were supplemented with 1 mL intraperitoneal injections of NaCl and compared to non-supplemented control mice. Mouse behavior and locomotive activity were assessed on days 5-6 after DSS initiation by means of tail suspension, novel object recognition and open field activity tests. Mice were euthanized after either the acute (day 7) or the recovery phase (day 12) of colitis and inflammation, epithelial proliferation, and differentiation were assessed by means of histology, immunohistochemistry, quantitative PCR, and western blot. We found that fluid-supplemented mice had reduced signs of colitis with no alterations in behavior or locomotive activity. Furthermore, we observed an accelerated epithelial repair response after fluid hydration during the acute phase of colitis, characterized by increased crypt proliferation, activation of ERK1/2, and modulation of TGF-β1 expression. Consistent with these findings, fluid-supplemented mice had increased numbers of goblet cells, upregulated expression of differentiation markers for absorptive enterocytes, and reduced inflammation during the recovery phase. Our results show that fluid hydration does not reduce stress in DSS-treated mice but alters colitis evolution by reducing clinical signs and accelerating epithelial repair. These results argue against the routine use of fluid supplementation in DSS-treated mice.

Spinal cord stimulation (SCS) is a well-established therapy for chronic pain syndromes, with growing applicability to other conditions. Restless legs syndrome (RLS) is a widespread, chronic movement disorder managed primarily and incompletely by medication, and its etiology can be classified as idiopathic or secondary.

Surgical excision of fat fractures is often reserved for patients with large chronic deformities to improve cosmetic appearance. To our knowledge, the acute surgical management of a traumatic fat fracture has not been previously reported.

Several studies suggested that migraine attack onset shows a circadian variation; however, there has not been an overview and synthesis of these findings. A PubMed search with keywords "migraine" AND "circadian" resulted in ten studies directly investigating this topic. Results of these studies mostly show that migraine attacks follow a monophasic 24-hour cyclic pattern with an early morning or late night peak while other studies reported an afternoon peak and also a biphasic 24-hour cycle of attacks. The identified studies showed methodological variation including sample size, inclusion of medication use, comorbidities, and night or shift workers which could have contributed to the contradictory results. Several theories emerged explaining the diurnal distribution of migraine attacks suggesting roles for different phenomena including a morning rise in cortisol levels, a possible hypothalamic dysfunction, a circadian variation of migraine triggers, sleep stages, and a potentially different setting of the circadian pacemaker among migraineurs. At the moment, most studies show an early morning or late night peak of migraine attack onset, but a significant amount of studies reveals contradictory results. Further studies should investigate the arising hypotheses to improve our understanding of the complex mechanism behind the circadian variation of migraine attacks that can shed light on new targets for migraine therapy.

Extracellular RNA in circulation mediates intercellular communication in normal and pathological processes. One mode of circulating miRNA transport in bodily fluids is within 30-150 nm small extracellular vesicles (sEVs) or exosomes. Uptake of sEVs can regulate gene expression in recipient cells enabling circulating miRNAs to exert paracrine and systemic effects. Complex regional pain syndrome (CRPS) is a debilitating pain disorder characterized by chronic inflammation. Our previous investigations identified a significant decrease of hsa-miR-939 in whole blood from CRPS patients compared to control; we also observed that overexpression of miR-939 can negatively regulate several proinflammatory genes . Though downregulated in whole blood, miR-939 was significantly upregulated in sEVs isolated from patient serum. Here we investigated miR-939 packaging into sEVs under inflammation induced by monocyte chemoattractant protein-1 (MCP-1), a chemokine that is upregulated in CRPS patients. Stimulation of THP-1 monocytes by MCP-1 led to elevated levels of miR-939 in sEVs, which was abrogated using inhibitors of exosome secretion. miRNAs loaded into exosomes largely contain short miRNA sequence motifs called EXOmotifs. Mutation analysis of miR-939 showed that EXOmotif is one of the possible cellular mechanisms responsible for packaging miR-939 into sEVs. We confirmed gene expression changes in recipient cells following the uptake of sEVs enriched in miR-939 using RNA sequencing. Additionally, our data from primary immune cell-derived sEVs of CRPS patients and controls demonstrate that while the relative expression of miR-939 is higher in sEVs derived from B cells, T cells and NK cells relative to monocyte-derived sEVs in controls, only the B cell-derived sEVs showed a significantly higher level of miR-939 in CRPS patients. Differential miRNA sorting into exosomes and its functional impact on recipient cells may contribute to the underlying pathophysiology of CRPS.