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Most patients with chronic plaque psoriasis receive topical treatment; however, available options lack a balance of efficacy with long-term safety and tolerability. Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 (PDE4) inhibitor approved by the US FDA for treatment of psoriasis.

The TWIK-related spinal cord K channel (TRESK) is part of the two-pore domain K channel family (K), which are also called leak potassium channels. As indicated by the channel family name, TRESK conducts K ions along the concentration gradient in a nearly voltage-independent manner leading to lowered membrane potentials. Although functional and pharmacological similarities exist, TRESK shows low sequence identity with other K channels. Moreover, the channel possesses several unique features such as its sensitivity to intracellular Ca ions, that are not found in other K2P channels. High expression rates are found in immune-associated and neuronal cells, especially in sensory neurons of the dorsal root and trigeminal ganglia. As a consequence of the induced hyperpolarization, TRESK influences neuronal firing, the release of inflammatory mediators and the proliferation of distinct immune cells. Consequently, this channel might be a suitable target for pharmacological intervention in migraine, epilepsy, neuropathic pain or distinct immune diseases. In this review, we summarize the biochemical and biophysical properties of TRESK channels as well as their sensitivity to different known compounds. Furthermore, we give a structured overview about the physiological and pathophysiological impact of TRESK, that render the channel as an interesting target for specific drug development.

Collagenous gastroduodenitis is a rare gastrointestinal disease diagnosed histologically by subepithelial collagen deposition in the lamina propria. Its clinical presentation is diverse. The authors encountered a 17-year-old female patient who complained of epigastric pain. Endoscopy revealed several deep ulcers in the gastric body. The gastric mucosa around the ulcer showed diffuse fine nodularity in the shape of cobblestones with open-type atrophy. The duodenal mucosa showed nodular lesions similar to those of the gastric mucosa. The gastric ulcer healed completely with proton pump inhibitor treatment. The patient was followed up, showing no remarkable mucosal change of stomach or duodenum for several years. Collagenous gastroduodenitis was diagnosed by repeated histologic examinations. This paper reports a rare case of chronic collagen gastritis with deep gastric ulcer and its long-term clinical progress.

Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial). 21,315 participants (aged 60-84 years) were randomly assigned to a monthly dose of 60,000 IU vitamin D3 or a matching placebo. Pain was measured using the 6-item Pain Impact Questionnaire (PIQ-6), administered 1, 2 and 5 years after enrollment. We used regression models (linear for continuous PIQ-6 score and log-binomial for binary categorizations of the score, namely 'some or more pain impact' and 'presence of any bodily pain') to estimate the effect of vitamin D on pain. We included 20,423 participants who completed ≥1 PIQ-6. In blood samples collected from 3943 randomly selected participants (∼800 per year) the mean (SD) 25(OH)D concentrations were 77 (SD 25) and 115 (SD 30) nmol/L in the placebo and vitamin D groups, respectively. Most (76%) participants were predicted to have 25(OH)D concentration >50 nmol/L at baseline. The mean PIQ-6 was similar in all surveys (∼50.4). The adjusted mean difference in PIQ-6 score (vitamin D cf placebo) was 0.02 (95% CI, -0.20 to 0.25). The proportion of participants with some or more pain impact and with presence of bodily pain was also similar between groups (both prevalence ratios 1.01, 95% CI 0.99 to 1.03). In conclusion, supplementation with 60,000 IU of vitamin D3 per month had negligible effect on bodily pain.

Pyoderma gangrenosum (PG) is a rare inflammatory skin disease that is difficult to diagnose. PG may be an extra-intestinal manifestation of ulcerative colitis (UC). In recent times, coronavirus disease (COVID-19) vaccines have caused various adverse cutaneous reactions. However, to the best our knowledge, combinations thereof have not been reported. We encountered a case of PG triggered by COVID-19 vaccination in a patient with UC. A 40-year-old woman developed severe pain and an abscess in the dorsum of the left foot after receiving the first dose of the messenger RNA (mRNA)-based Pfizer/BioNTech BNT162b2 COVID-19 vaccine. Severe painful ulcers with purulent necrosis and gaseous gangrene progressed rapidly along the extensor tendons and muscles to the toes and ankle. Although surgical debridement can worsen PG by triggering pathergy, we nonetheless performed wide debridement including partial extensor tenotomy with abscess drainage to prevent progression to pyogenic ankle arthritis and to rescue the toes. Antibiotics, corticosteroids, and anticoagulants were prescribed during surgical wound management via negative pressure therapy. After the lesion improved, the skin and soft tissue defect were covered using a superficial circumflex iliac artery perforator free flap and a split-thickness skin graft. The patient was satisfied with the foot salvage, and could walk unaided (without a brace or cane) from 8 weeks after the final surgery. PG may be rare even in UC patients, but mRNA-based COVID-19 vaccines may find an immunosuppressive niche. A high level of caution and suspicion of skin manifestations after vaccination is essential.

Single studies support the presence of several post-COVID-19 symptoms; however, there is no evidence for the synthesis of symptoms.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator that regulates the cerebrovascular and peripheral circulation. A new class of migraine therapies decreases CGRP through various mechanisms. One unknown off-target effect is the impact decreasing CGRP will have on the peripheral circulation. The following cases report new onset Raynaud's phenomenon (RP) following the use of CGRP receptor antagonists (-gepants) for both the acute and preventive treatment of migraine. These cases describe the development of RP in two individuals after using each of the currently available gepant medications. To our knowledge these are the first cases reported of RP associated with the use of gepants. RP has previously been reported in association with monoclonal antibodies to the CGRP ligand and CGRP receptor indicated in the prevention of migraine.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disorder which harm exocrinic glands located mainly in the oral and ocular regions. pSS patients often complain about pain and mouth dryness. The aim of this retrospective study was to evaluate the influence of parotid glands' sialendoscopy on salivary flow in pSS patients and to assess the tissue characteristics of the parotid glands during the sialendoscopy procedure.

More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups.

Around 10% of adults infected with SARS-CoV-2 that survive a first episode of COVID-19 appear to experience long-term clinical manifestations. The signs and symptoms of this post-acute COVID-19 syndrome (PACS) include fatigue, dyspnea, joint pain, myalgia, chest pain, cough, anosmia, dysgeusia, headache, depression, anxiety, memory loss, concentration difficulties, and insomnia. These sequelae remind the constellation of clinical manifestations previously recognized as myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). This condition has been described following distinct infectious events, mostly acute viral illnesses. In this way, the pathophysiology of PACS might overlap with mechanisms involved in other post-infectious fatigue syndromes. The risk of PACS is more frequent in women than men. Additional host genetic factors could be involved. There is a dysregulation of multiple body organs and systems, involving the immune system, the coagulation cascade, endocrine organs, autonomic nervous system, microbiota-gut-brain axis, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, etc. Hypothetically, an abnormal response to certain infectious agents could trigger the development of postinfectious fatigue syndromes.