Rejected

Sickle cell disease (SCD) induces chronic haemolytic anaemia and intermittent vaso-occlusion that results in tissue ischaemia causing acute, severe pain episodes that can lead to frequent hospitalizations. These consequences can have repercussions on family, social, school and/or professional life. Here, we present some of the results of the PHEDRE study (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease), which is the largest study of patients with SCD in France. This paper intends to describe characteristics of the French SCD population. We also aimed to assess the impact of the disease on the lives of patients using objective and subjective variables.

The application of topical diclofenac has been suggested as a possible treatment for Achilles tendinopathy. Our aim was to answer the question, is topical diclofenac more effective than placebo for the treatment of Achilles tendinopathy?.

5-Hydroxytryptophan (5-HTP) plays an important role in the regulation of emotion, behavior, sleep, pain, body temperature, and other physiological functions. It is used in the treatment of depression, insomnia, migraine, and other diseases. Due to a lack of effective biosynthesis methods, 5-HTP is mainly obtained by natural extraction, which has been unable to meet the needs of the market. Through the directed evolution of enzymes and the introduction of substrate supply pathways, 5-HTP biosynthesis and yield increase have been realized. This review provides examples that illustrate the production mode of 5-HTP and the latest progress in microbial synthesis.

Although numerous studies have looked at the numeric rating scale (NRS) in chronic pain patients and several studies have evaluated objective pain scales, no known studies have assessed an objective pain scale for use in the evaluation of adult chronic pain patients in the outpatient setting. Subjective scales require patients to convert a subjective feeling into a quantitative number. Meanwhile, objective pain scales utilize, for the most part, the patient's behavioral component as observed by the provider in addition to the patient's subjective perception of pain. This study aims to examine the reliability and validity of an objective Chronic Pain Behavioral Pain Scale for Adults (CBPS) as compared to the traditional NRS.

Primary headaches are remarkably prevalent worldwide and are increasingly reported among children. However, the exact trend in this age group, particularly in the Gulf region, remains largely unknown. To examine the prevalence of primary headache disorders among primary and middle school students in Kuwait. We conducted a cross-sectional study that included Kuwaiti primary and middle school children and adolescents of both genders in randomly selected schools located in two governorates in Kuwait in the 2018/2019 academic year. Prevalence and attributable burden of headaches, definite and probable migraines, definite and probable tension-type headaches, chronic headaches (≥15 days/month), and probable medication-overuse headaches were assessed using the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Of 1,485 questionnaires that were distributed, 1,089 students completed the questionnaire with a respondent rate of 73.4%. The study population consisted of 420 boys (38.56%) and 669 girls (61.43%) students with a mean age of 11.5 ± 2.11 years. The 1-year prevalence of primary headache disorders was 42.78%, with more middle schoolers reporting headaches than primary schoolers (50.37 vs. 30.48%; < 0.02). The mean age of students with primary headaches was 11.98 ± 2.03 years in both genders. When stratified according to diagnostic criteria, migraine headaches were the most frequently reported (20.75%), followed by tension type headaches (18.8%), chronic headaches (2.75%), and probable medication-overuse headaches (0.46%). Primary headaches were significantly higher in girls compared to boys among middle schoolers (66.46 vs. 38.49%; < 0.001); however, no significant difference between genders was noted among primary school students (33.12 vs. 22.33%; < 0.118). Primary headaches are remarkably common in Kuwaiti school students, with migraine headaches being the most frequently reported type. Age and female gender may play a role in the development of primary headaches. These findings necessitate the direction of health services and research efforts toward this age group and warrant the need for further epidemiological studies.

A well-balanced intracellular iron trafficking in glial cells plays a role in homeostatic processes. Elevated intracellular iron triggers oxidative stress and cell damage in many neurological disorders, including migraine. This study aimed to investigate the effects of glyceryl trinitrate (GTN), on cellular iron homeostasis, matrixmetalloproteinase (MMP)-9, and calcitonin gene related peptide (CGRP) receptor (CRLR/CGRPR1) production in microglia, astrocyte, and meningeal cell cultures. Primary glial and meningeal cells in culture were exposed to GTN for 24 h. Messenger RNA expression was assessed using qPCR. Iron accumulation was visualized via modified Perl's histochemistry. MMP-9 levels in cell culture supernatants were measured using ELISA. Ferritin and CRLR/CGRPR1 proteins were visualized via immunofluorescence staining. Nitric oxide production increased significantly with GTN in meningeal and glial cells. GTN significantly increased the expression of the storage protein ferritin for all three cell types, but ferritin-L for meningeal cells and microglia. Iron trafficking associated with the efflux protein ferroportin and influx protein divalent metal transporter (DMT)1 was affected differently in all three cell types. MMP-9 expression was increased in astrocytes. GTN stimulation increased both CRLR/CGRPR1 expression, and immunostaining was apparent in microglia and meningeal cells. This study showed for the first time that GTN modulates intracellular iron trafficking regulated by storage and transport proteins expressed in meningeal cells and glia. CRLR/CGRPR1 expression might be related to altered iron homeostasis and they both may stimulate nociceptive pathways activated in migraine. These molecules expressed differently in glial and meningeal cells in response to GTN may bring not only new targets forward in treatment but also prevention in migraine.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with advanced non-small-cell lung cancer (aNSCLC), but immune-related adverse events (irAEs) have been evidenced curtailed the clinical use of them.

This is an unusual case of an obstructive rectal squamous cell carcinoma (SCC), causing perforation and a pelvic abscess, requiring source control and diverting colostomy. A 50-year-old female with chronic constipation presented with worsening right buttock pain for 1 month. On exam, the patient reported right hip tenderness. A computer tomography (CT) revealed rectal wall thickening with a presacral abscess. Due to the concern of rectal perforation with abscess she was taken to the operating room for proctoscopy with biopsy, colostomy diversion and drainage of the abscess over the right buttock. Pathology reported invasive rectal SCC. Rectal SCC presents similarly to rectal adenocarcinoma but its diagnosis must include special markers for cytokeratins. The treatment approach is controversial but adequately treated offers better survival than rectal ADC. Rectal SCC is rare and treated with chemoradiation however it must also be tailored to the variable acute presentations.

Chronic skin wounds represent a major global health problem and financial burden. The blocked healing process of chronic wounds involves excess inflammatory proteins, persistent microbial burden, and often, drug-resistant biofilm on the wound bed. Wound-bed debridement is considered crucial to restart the healing process.

We describe a case of a mucosal prolapse syndrome (MPS)-like inflammatory polyp protruding from the appendiceal orifice, mimicking an appendiceal neoplasm. A 48-year-old man presented with lower abdominal pain and elevated white blood cell count and C-reactive protein level. Computed tomography showed a swollen appendix with multiple small saccular lesions and periappendiceal fat stranding and small saccular lesions in the ascending colon and cecum. Ultrasonography showed a swollen appendix 25 mm in diameter with multiple saccular structures and a periappendiceal high-echoic area, suggesting appendiceal diverticulitis. Colonoscopy revealed an erythematous lesion protruding from the appendiceal orifice. An ileocecal resection was performed based on a preoperative diagnosis of appendiceal diverticulitis and tumor. Histopathological examination of the appendix showed multiple mucosal herniations with infiltration of inflammatory cells, indicating appendiceal diverticulitis. The tumor was characterized by glandular duct hyperplasia and stromal expansion with smooth muscle hyperplasia and was diagnosed as an inflammatory polyp resembling an MPS lesion. Although several studies have shown the macroscopic and endoscopic appearance of MPS-like inflammatory lesions associated with colonic diverticular disease, this case was the first to present an inflammatory polyp associated with appendiceal diverticulitis in which the lesion protruding from the appendiceal orifice was masquerading as an appendiceal neoplasm.