Rejected

Klippel-Feil syndrome (KFS) is defined by multiple abnormal segments of the cervical spine with congenital synostosis of two or more cervical vertebrae. KFS patients who demonstrate progressive symptomatic instability and/or neurologic sequelae are traditionally managed with operative decompression and arthrodesis.

In the Corona Virus Disease 2019 (COVID-19) pandemic, the primary problem is respiratory-related, but there also is increasing evidence of central nervous system (CNS) involvement. This study aims to summarize the literature on neurological manifestations of COVID-19, underlying mechanisms of CNS involvement and cognitive consequences.

Hypotension following major abdominal surgery is common, and once hypovolaemia has been optimally treated, is often due to vasodilation which can be treated with vasopressor infusions. There is unpredictability in the dose and duration of post-operative vasopressor infusions, and factors associated with this have not been determined.

Colon cancer is a rare diagnosis in 30-year-old women, which may be further complicated by their concurrent gravid status. Several physiological changes that occur during an intrauterine pregnancy (IUP) can mask symptoms of early colon cancer. Our patient was a 30-year-old, Gravida 2, Para 0 woman with an uncomplicated pregnancy until the 35 week of gestation when she developed preeclampsia and symptoms suggestive of early hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome. Following induction of labor and the subsequent, uncomplicated vaginal delivery, the patient developed symptoms of nausea, vomiting, and constipation with abdominal pain and bloating. Abdominal computed tomography (CT) revealed a large mass in the right colon along with the involvement of periaortic lymph nodes and the presence of liver metastases. Hepatic metastases were possibly responsible for the patient's elevated liver enzyme levels, which were initially considered to have been caused by HELLP syndrome because the patient also had preeclampsia. The rarity of colon cancer in young, pregnant patients with no family history, such as in this case, results in poor prognosis owing to nonspecific symptoms of the developing malignancy being attributed to pregnancy, which further delays diagnosis and subsequent therapy. Of 29 cases of colon cancer in pregnant patients recorded till date, this is the first report of a stage 4 adenocarcinoma of the colon with hepatic metastasis, elevated liver enzyme levels, and increased blood pressure with associated preeclampsia, which was diagnosed in the postpartum period. It may be important to consider broader differential diagnoses in expectant patients presenting with unusual and persistent symptoms.

Bladder pain syndrome (BPS) is a chronic condition characterized by pelvic pain or pressure which is perceived to be originating from the bladder, accompanied by one or more urinary symptoms, including frequency, urgency and nocturia. The precise etiology of BPS is not fully understood. Chronic bacterial infection, defective glycosaminoglycan (GAG) layer of the bladder urothelium, inappropriate activation of mast cells in the suburothelial layer of the bladder, autoimmune-mediated mechanisms and autonomic nervous system dysfunction have all been implicated. Treatments targeted at each of these mechanisms have been developed with mixed outcomes. High-quality research into the treatment options is lacking and it is difficult to draw definite conclusions. The treatment approach is multimodal and should be patient specific, targeting the symptoms which they find most bothersome. Conservative treatment, including patient education, behavioural modification, dietary advice, stress relief and physical therapy is an essential initial management strategy for all patients. If no response is observed, oral treatments such as amitriptyline are likely to offer the greatest response. Cystoscopy is essential to phenotype patients, and Hunner lesion directed therapy with fulguration or resection can be performed at the same time. Intravesical instillation of DMSO or lidocaine, detrusor injections of botulinum toxin A and neuromodulation can be used if initial management fails to improve symptoms. Oral cyclosporin can be trialled in those experienced with its use; however, it is associated with significant adverse events and requires intense monitoring. Lastly, radical surgery should be reserved for those with severe, unremitting BPS, in which quality of life is severely affected and not improved by previously mentioned interventions. Future work investigating exact aetiological factors will help target the development of efficacious treatment options, and several promising oral and intravesical treatments are emerging.

Hypertrophic pachymeningitis (HP) is generally regarded as a rare inflammatory disease, which results in a diffuse thickening of the dura mater. We retrospectively collected data from patients with HP.

As a degenerative joint disease with severe cartilage destruction and pain, osteoarthritis (OA) has no satisfactory therapy to date. In traditional Chinese medicine (TCM), Debeaux derived () has been developed for joint pain treatment. However, it causes adverse events in OA patients. Long-time decoction has been traditionally applied to reduce the aconite toxicity of and other aconite herbs, but its detoxifying effect is uncertain.

Interleukin-15 (IL-15) is a pro-inflammatory cytokine that is increased in joint fluids of early-stage osteoarthritis (OA) patients, and has been associated with expression of proteases that can damage cartilage, and the development of neuropathic pain-like symptoms (NP) after nerve injury. The objective of this study was to further explore the role of IL-15 in the pathogenesis of OA cartilage degeneration and test genetic variation in the IL-15 receptor α gene () for an association with OA with radiographic severity and symptoms. Cartilage samples from donors ( = 10) were analyzed for expression of the IL15 receptor α-chain using immunohistochemistry, and for responses to IL-15 using explant cultures. Data from two independent Nottinghamshire-based studies ( = 795 and = 613) were used to test genetic variants in the gene (rs2228059 and rs7097780) for an association with radiographic severity, symptomatic vs. asymptomatic OA and NP. IL-15Rα was expressed in chondrocytes from cartilage obtained from normal and degenerative knees. IL-15 significantly increased the release of matrix metalloproteinase-1 and -3 (MMP-1 and -3), but did not affect loss of proteoglycan from the articular matrix. Genetic variants in the gene are associated with risk of symptomatic vs. asymptomatic OA (rs7097780 OR = 1.48 95% 1.10-1.98 < 0.01) and with the risk of NP post-total joint replacement (rs2228059 OR = 0.76 95% 0.63-0.92 < 0.01) but not with radiographic severity. In two different cohorts of patients, we show an association between genetic variation at the IL15 receptor and pain. Although cartilage explants could respond to IL-15 with increased protease production, we found no effect of IL-15 on cartilage matrix loss and no association between variants and radiographic severity. Together, these results suggest that IL-15 signaling may be a target for pain, but may not impact structural progression, in OA.

The prevalence of primary headaches in the pediatric population is shaped by many factors, of which pubertal status may possibly play a substantial role. Epidemiological studies in the pediatric population in the gulf region remain scarce. To examine the impact of puberty on the prevalence of primary headache disorders among female schoolchildren in Kuwait. We conducted a cross-sectional study that included Kuwaiti primary and middle schoolgirls in randomly selected schools located in two governorates in Kuwait during the academic year 2018/2019. Prevalence of headache was assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Female students were asked about their menarchal status and whether they attained menarche before or after experiencing headaches. The questionnaire was completed by 669 girls with a mean age of 11.44 ± 2.14 years. The 1-year prevalence of migraine headache disorder among girls was 23.62%, and the lifetime prevalence of any headache was 84.9%, whereas the 1-year prevalence of primary headache disorders was 47.98%. The mean age of girls with headaches was 11.44 ± 2.14 years. With respect to diagnostic criteria, migraine headache was the most frequently reported (23.62%), followed by tension-type headaches (20.93%), chronic headaches (2.99%), and probable medication-overuse headaches (0.45%). Postpubertal females were at significantly higher risk of having primary headaches compared to their prepubertal counterparts (64.26 vs. 34%; < 0.0001). All types of primary headaches were more significantly prevalent among postpubertal girls compared to those who are prepubertal. Migraine headache is commonly reported among Kuwaiti schoolgirls. Postpubertal females are at higher risk of developing primary headaches compared to prepubertal females. Pubertal transition and female sex hormones may play a significant role in the pathophysiology of headaches, migraines in particular, and further research is therefore needed to investigate the underlying mechanisms.

Eculizumab has been developed as a breakthrough treatment for paroxysmal nocturnal hemoglobinuria (PNH). Not only for breakthroughs, eculizumab therapy is also known to increase the risk of invasive meningococcal infection. It has also been recently reported that, although rarely, administration of eculizumab may result in disseminated gonococcal infection (DGI). We report here a case in which a young patient who had used eculizumab for PNH developed DGI. A 22-year-old Japanese male with PNH who had been treated with eculizumab complained of high fever, mild nausea, headache and right knee joint pain. The patient was admitted and suspected to have sepsis due to meningococcal infection and began to receive ceftriaxone (CTRX). Gonococci were detected in a venous blood culture a few days later, and this case was diagnosed as DGI. CTRX was effective, and the patient was discharged. However, four weeks later, he complained of the same subjective symptoms as at the beginning and was hospitalized again. The presence of gonococcus was proven by venous blood culture, CTRX was re-administered and the patient responded. After discharge, he was counseled on safer sexual activity, including accurate and consistent use of condoms, by urologists. He has not relapsed with DGI for more than one year. When serious signs of infection occur in patients receiving eculizumab, it is recommended to consider DGI as well as invasive meningococcal infection, and CTRX should be given.