Rejected

To report a case of petrous apicitis that manifested as chronic migraine without aura and to discuss the pathophysiological mechanisms behind this presentation.

Rheumatoid arthritis (RA) is a systemic, autoimmune disease that affects joints and extra-articular structures. In the last decade, the management of this chronic disease has dramatically changed with the introduction of several targeted mechanisms of action, such as tumor necrosis factor-α inhibition, T-cell costimulation inhibition, B-cell depletion, interleukin-6 blockade, and Janus kinase inhibition. Beyond its well-known hematopoietic role on the proliferation and differentiation of myeloid cells, granulocyte-monocyte colony-stimulating factor (GM-CSF) is a proinflammatory mediator acting as a cytokine, with a proven pathogenetic role in autoimmune disorders such as RA. In vitro studies clearly demonstrated the effect of GM-CSF in the communication between resident tissue cells and activated macrophages at chronic inflammation sites, and confirmed the elevation of GM-CSF levels in inflamed synovial tissue of RA subjects compared with healthy controls. Moreover, a pivotal role of GM-CSF in the perception of pain has been clearly confirmed. Therefore, blockade of the GM-CSF pathway by monoclonal antibodies directed against the cytokine itself or its receptor has been investigated in refractory RA patients. Overall, the safety profile of GM-CSF inhibitors seems to be very favorable, with a particularly low incidence of infectious complications. The efficacy of this new mechanism of action is comparable with main competitors, even though the response rates reported in phase II randomized controlled trials (RCTs) appear to be numerically lower than the response rates observed with other biological disease-modifying antirheumatic drugs already licensed for RA. Mainly because of this reason, nowadays the development program of most GM-CSF blockers for RA has been discontinued, with the exception of otilimab, which is under evaluation in two phase III RCTs with a head-to head non-inferiority design against tofacitinib. These studies will likely be useful for better defining the potential role of GM-CSF inhibition in the therapeutic algorithm of RA. On the other hand, the potential role of GM-CSF blockade in the treatment of other rheumatic diseases is now under investigation. Phase II trials are ongoing with the aim of evaluating mavrilimumab for the treatment of giant cell arteritis, and namilumab for the treatment of spondyloarthritis. Moreover, GM-CSF inhibitors have been tested in osteoarthritis and diffuse subtype of systemic sclerosis. This review aims to describe in detail the available evidence on the GM-CSF blocking pathway in RA management, paving the way to a possible alternative treatment for RA patients. Novel insights regarding the potential use of GM-CSF blockers for alternative indications will be also addressed.

A 59-year-old patient with no history of rheumatic musculoskeletal disease was diagnosed with metastatic melanoma and was being treated with the monoclonal antibody to PD-1, nivolumab, a checkpoint inhibitor. Whilst undergoing the treatment he developed widespread painful stiffness with reduced movement of the neck. The pain occurred mostly at night and he reported morning stiffness of up to 3 hours. The clinical examination revealed a reduced range of motion of the neck. Laboratory tests showed raised inflammatory markers. This article is protected by copyright. All rights reserved.

We report a case of a 13-year-old girl who presented with a 2-month history of intermittent abdominal pain. Laboratory examination showed hepatitis and pancreatitis. Because of persistent vomiting, computed tomography (CT) was performed, which revealed a circumferential soft tissue density in the duodenal wall, causing partial obstruction. Supportive therapy failed. Repeat CT showed no significant change from the initial study. The patient underwent upper endoscopy, which revealed a mass in the second portion of the duodenum, which occluded most parts of the lumen. The histopathological finding was consistent with an anaplastic large cell lymphoma, a rare form of small bowel neoplasm. After the third course of chemotherapy, complete resolution of the mass was noted, and her symptoms were relieved.

Low back pain (LBP) is a highly prevalent chronic pain condition with a neuropathic component of pain that limits the benefits of classical opioids. Tapentadol is an innovative drug for the treatment of chronic severe pain, with a dual mechanism of action combining µ-opioid receptors agonism and noradrenaline re-uptake inhibition (NRI). Its efficacy is equal to that of strong opioids, with a better tolerability profile and a consequently lower risk of treatment discontinuation. The aim of this study was to evaluate the analgesic efficacy and tolerability of tapentadol prolonged release (PR) vs. other analgesics in patients with moderate-to-severe neuropathic low back pain, before and after back surgery.

The efficacy of dexketoprofen for migraine attack remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexketoprofen supplementation versus placebo on pain control in migraine attack patients.

Botulinum toxin (Botox) was introduced for the management of internal anal sphincter (IAS) achalasia after a pull-through procedure in Hirschsprung disease (HD). We conducted a prospective evaluation of the efficacy and safety of this Botox treatment.Our study group included 15 patients with HD (median age, 4.8 years; range, 1.7-7.4 years) who experienced persistent constipation after pull-through surgery. Rectal biopsy and colon study were performed before Botox injection to exclude agangliosis. Intersphincteric Botox injections (dose, 4 IU/kg) were performed at 3 sites, (3, 6, and 9 o'clock) under general anesthesia. Measured outcomes of efficacy included anorectal manometry, Wexner constipation score and the quality of life score for defecation, measured at baseline and at 2 weeks and 3 months after injection. The Holschneider incontinence score and an assessment of pain, bleeding, heating sensation, and swelling were also performed at follow-up as outcomes of safety.There was no significant change in measured outcomes with Botox treatment. Botox did decrease the number of patients who experienced abdominal distension at 3 months, compared to 2-weeks, post-injection. No major complications were identified, with only 2 cases of anal bleeding that resolved spontaneously. Local tenderness at the injection site was reported by 4 patients, recovering without treatment.The efficacy of Botox, injected into the IAS, for the treatment of achalasia is questionable on short-term follow-up. Larger studies with a longer follow-up period and the use of repeated injections are required to evaluate the evidence for this treatment.

Serratus anterior plane block has been used for pain management during the acute period of conditions affecting the thorax, such as postthoracotomy recovery, rib fracture, and breast surgery recovery. Here, we report the use of serratus anterior plane block in posttraumatic chronic pain treatment. We describe a case of posttraumatic chronic intercostal neuralgia, in which successful pain relief was achieved via repeated injections of local anesthetic and steroid combinations in the serratus anterior plane under ultrasonographic guidance. This novel technique is easy to administer, reliable, and warrants further investigation with regard to its use for rehabilitation of patients who are experiencing posttraumatic chronic neuropathies of the chest wall.

To identify clinical risk factors associated with development of delayed-onset postpartum preeclampsia, and to characterize management and subsequent risk of cardiovascular disease.

Calciphylaxis is a rare disorder of poor prognosis that can lead to intense, painful lesions involving the skin and subcutaneous tissue. Although mostly described in dialysis patients, it can affect patients with normal kidney function. The diagnosis of calciphylaxis is complicated by the absence of a gold standard marker of disease such as a clear histopathological finding. Late diagnosis and advanced lesions can significantly shorten life expectancy. Calciphylaxis wounds can have a major influence on the quality of life of patients, usually due to the immense unbearable pain these patients suffer from. The management of calciphylaxis mainly comprises aggressive wound care and symptomatic management. Therapeutic options are few and far between and are limited to off-label uses. Recent understanding of the pathogenesis of lesions has enabled development of novel therapeutic options, some of which are being studied in clinical trials (sodium thiosulfate, vitamin K). Vascular calcification and thrombosis underlie development of these lesions and research has been aimed at studying drugs that counteract such processes. Future research is required to establish clear causal pathways and improve on the treatment options currently available to patients.