Rejected

BACKGROUND This study aimed to identify NOTCH3 mutations and describe the genetic and clinical features and magnetic resonance imaging results in 11 unrelated patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from Henan province in China. MATERIAL AND METHODS NOTCH3 was directly sequenced in 11 unrelated patients of Chinese descent. The clinical presentations and magnetic resonance imaging features were retrospectively analyzed in the 11 index patients with a definite diagnosis. RESULTS Seven different mutations were identified in 11 unrelated patients, including 4 novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) in China and 3 reported mutations (p.C117R, p.R578C, and p.R607C). Four novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) were predicted to be probably pathogenic using an online pathogenicity prediction program through comprehensive analysis. Clinical presentations in symptomatic patients included stroke, cognitive decline, psychiatric disturbances, and migraine. Multiple lacunars infarcts and leukoaraiosis were detected on MRI in most symptomatic patients, while white-matter lesions were identified in the temporal pole or the external capsule in all affected patients. CONCLUSIONS The mutation spectrum of CADASIL patients from Henan province in China displayed some differences from that of those reported previously. DNA sequencing was used to diagnose all 11 patients as having CADASIL, and we found 4 novel mutations. The present results further contribute to the enrichment of NOTCH3 mutation databases.

Functional abdominal pain disorders (FAPD) have been widely reported as a major group of gastrointestinal disorders across the world. This study describes the prevalence, related factors, symptomatology and its relationship to emotional stress in Indonesian adolescents.

An 80-year-old woman presented with chest pain and dyspnea. The electrocardiogram (ECG) showed a known chronic complete left bundle branch block and elevated levels of high-sensitivity cardiac Troponin T. The first diagnosis was acute coronary syndrome, but a few hours later she developed shock and syncope; after resuscitation a coronary angiography was performed but it did not show any acute coronary obstruction. The echocardiogram showed McConnell's sign suggesting a massive pulmonary embolism; the pulmonary angiography showed large thrombi in both branches of pulmonary artery, so a catheter-based treatment was performed with thromboaspiration and rt-PA administration, and a significant improvement of blood pressure, clinical condition and right ventricle function was observed. In spite of bleeding at the puncture sites (femoral artery and vein), controlled by local compression, catheter-based therapy in massive pulmonary embolism was associated with survival and satisfactory outcome. A combined fragmentation/thromboaspiration and catheter-directed fibrinolysis strategy may be useful to reduce the embolic load, improve RV function, and reduce mortality.

Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety of tofacitinib have been shown in several randomized clinical trials. The study presented here aimed to assess the clinical tolerability and effectiveness of tofacitinib among RA patients in real life. Consecutive patients between January 2015 and April 2017 with RA who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria were included in a prospectively designed analysis of retrospective data. Patients were initiated on tofacitinib 5 mg bid. The primary objective was to analyze the safety of tofacitinib in a real-life cohort. Safety was assessed by the reasons to stop tofacitinib during follow up and changes of liver enzymes, hemoglobin, and creatinine. The secondary outcome was to analyze the frequency of and time to achieve low disease activity (LDA) and remission as defined by 28 joint count disease activity score (DAS28). A total of 144 patients were treated with tofacitinib. A total of 84.9% of patients were pre-exposed to at least one biological agent. The average DAS28 at the initiation of tofacitinib was 4.43. A total of 50.0% of patients were positive for rheumatoid factor and 49.0% for ACPA. The mean follow up was 1.22 years (range 10d-3.7a) after initiation of tofacitinib treatment. A total of 94 (64.4%) patients remained on tofacitinib during follow-up. The average time to stop tofacitinib was 190.0 days. Reasons to stop tofacitinib were: insufficient response (n = 23), gastrointestinal symptoms (n = 18), infection ( = 5), myalgia ( = 2), remission ( = 2), headache ( = 2), cough, blue finger syndrome, intolerance, heartburn, psoriasis, and increased liver enzymes (all = 1). Increased alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2× upper limit of normal (ULN) were detected in 3.3% and 4.4% of patients, respectively. Hemoglobin decrease of >10% was detected in 15.1% of the patients and decreased lymphocytes <500/μL in 3.4%. An increase of creatinine >20% was detected in 9.4% of patients. A total of 62.9% and 50.0% of the patients achieved low disease activity (LDA) or remission after a median of 319 and 645 days, respectively. These rates were significantly higher in patients naïve to biologic agents as compared to patients pre-exposed to biologics (LDA: naïve 100% 92 d, pre-exposed 57.0% 434 d, p ≤ 0.001; remission: naïve 86.7% 132 d, pre-exposed 44.1%, 692 d, p = 0.001). Tofacitinib is a safe and effective treatment option for patients with RA. Tofacitinib may induce high rates of LDA and remission in patients with active disease, even after the use of one or more biologics, though the rate appeared higher in patients naïve to biologics. Tofacitinib may be a valuable option in a treat-to-target approach. Our data demonstrate that Janus kinase (JAK) inhibitors are safe and efficacious in real life patients.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized oftentimes by symmetrically distributed, severely pruritic nodules. Currently, the pathophysiology of PN remains to be fully elucidated, but emerging evidence suggests that neuroimmune alterations play principal roles in the pathogenesis of PN. There are several associated etiologic factors thought to be associated with PN, including dermatoses, systemic, infectious, psychiatric, and neurologic conditions. We conducted a systematic literature review to evaluate the clinical presentation, diagnosis, and etiologic factors of PN. In this review, we discuss common differential diagnoses of PN and recommend an evidence-based, standardized diagnostic evaluation for those with suspected PN.

Nursing staff in all settings have multiple work-related problems due to patient handling and occupational stressors, which result in high stress levels and low back pain. In this context the importance of health promotion becomes apparent. The aim of this study is to analyse whether nursing staff (in elderly care, hospitals, home care, or trainees) show different levels of work-related burdens and whether they require individualized components in health promotion programs. N = 242 German nurses were included in a quantitative survey (Health survey, Screening Scale (SSCS) of Trier Inventory for Chronic Stress, Slesina). The differences were tested using Chi-Tests, Kruskal-Wallis Test and one-way ANOVA. Nurses differed in stress loads and were chronically stressed (F = 5.775, = 0.001). Nurses in home care showed the highest SSCS-values with time pressure as the most important straining factor. The physical strains also placed a particular burden on nurses in home care, whereas they still reported higher physical well-being in contrast to nurses in elderly care (Chi = 24.734, < 0.001). Nurses in elderly care and home care preferred strength training whereas nurses in hospitals and trainees favoured endurance training. Targeted programs are desirable for the reduction of work-related burdens. While nurses in elderly care and home care need a combination of ergonomic and strength training, all nurses require additional stress management. Planning should take into account barriers like perceived additional time consumption. Therefore, health promotion programs for all settings should be implemented during working time at the work setting and should consider the working schedule.

Pain is recognized as one of the main symptoms in knee osteoarthritis and is the main reason why patients seek medical attention. has been popularly used to relieve discomfort caused by various painful conditions. The objective of the study is to evaluate the analgesic and anti-inflammatory effect of the crude extract of , in an experimental model of osteoarthritis. The experiment was performed with Wistar rats divided into 4 groups with 5 animals each: healthy, saline, crude extract, and meloxicam groups. Knee osteoarthritis was induced by intra-articular injection of sodium mono-iodoacetate. First, clinical parameters of pain were assessed at days 0, 5, 10, 15, and 20 after induction. Second, the potential cyclooxygenase inhibition was evaluated, and the cytokines of the synovial fluid were quantified. An in silico test and Molecular Docking tests were performed. A histopathological evaluation was made on articular cartilage with safranin O staining. The results showed that a 15-day treatment with crude extract reduced edema, spontaneous pain, peripheral nociceptive activity, and proinflammatory cytokines in the synovial fluid. The highest inhibition of cyclooxygenase 2 in the crude extract occurred at 50 µg/mL. The crude extract of presents therapeutic potential for the treatment of osteoarthritis due to its anti-inflammatory and anti-nociceptive action.

Background Prolactin-secreting pituitary adenomas in childhood and adolescence are rare. First-line therapy consists of dopamine agonists (DAs) like cabergoline. Experience in treating prolactinomas in paediatric and adolescent patients is limited. Methods This study was a retrospective analysis of clinical data, laboratory data, radiological findings and medical treatment of paediatric and adolescent patients with prolactinomas between 2009 and 2018. Results Our cohort of nine patients had a median age at diagnosis of 13 years (range 5-17). Main presenting symptoms were weight gain, disorders of the pituitary-gonadal axis and headache. Treatment with cabergoline resulted in a marked reduction in prolactin concentration in all nine patients. Tumour mass reduction was confirmed by magnetic resonance imaging (MRI) scan in seven patients. Noteworthy is that cabergoline therapy triggered frequent adverse effects in a total of eight patients – seven of whom suffered from mental disorders, five of whom had neurological symptoms and five of whom had gastrointestinal problems. The adverse effects occurred at a median dose of only 0.5 mg/week (range 0.25-2.0). Most symptoms were alleviated after the cabergoline dose was lowered. Therapy discontinuation was not necessary in any patient. Conclusions Cabergoline effectively lowers prolactin levels and may reduce tumour mass in paediatric and adolescent patients with prolactinomas. Potential adverse effects may include mental disorders and behavioural problems even at low cabergoline doses. Low starting doses and careful individual dose adjustments are required to enable therapy adherence.

Objective The goal of this study was to evaluate the presentation, management, and clinical outcome of nonfunctioning pituitary adenomas (NFPAs) in a tertiary care setup. Methods We conducted a retrospective review of patient records of 157 patients with the diagnosis of NFPA managed at Aga Khan University Hospital, a tertiary care hospital in Karachi, Pakistan from January 1, 2007, to December 31, 2017. We collected data on basic demographic characteristics, signs, and presenting symptoms, management, and outcomes. Data analysis was performed by using Stata, Version 12 (StataCorp LLC, College Station, TX). Results Most patients in the study were men (59%), and the mean age of the study population was 48 ± 14 years. The main presentations of NFPA were visual disturbance (77%) and headache (55%). In 78% of patients, the tumor was >1 cm on MRI. Most (87%) of patients underwent surgical resection, and of those, 93% received transsphenoidal surgery that was well tolerated. In the study population, 31% of patients had transient, 9% had permanent diabetes insipidus, and 25% developed hyponatremia. Of those in the study, 53% had low cortisol, 57% had hypothyroidism, and 27% needed sex hormone replacement after surgery. Residual tumor was confirmed in 43% of patients by postoperative MRI. Tumor recurrence and regrowth occurred in 17 patients and required repeat resection or radiosurgery. Conclusion In Pakistan, patients with NFPAs are more likely to present during the later stage, with larger adenoma and compressive symptoms compared to patients in developed countries. For the detection of residual disease and tumor recurrence, close screening and a multidisciplinary approach are needed after surgery.

Lyme disease is the most common vector-borne disease in the northern hemisphere. Neurological complications usually manifest in patients who do not receive treatment for Lyme disease. Neurological involvement may be early or late, depending on the duration of the symptoms. Early neuroborreliosis presents with symptoms such as headache and meningism; late neuroborreliosis can present with signs and symptoms of encephalopathy and stroke-like symptoms. The diagnosis is based on clinical manifestations and lumbar puncture finding. Treatment consists of intravenous antibiotics for a period of three to four weeks. Patients who receive early treatment usually have an excellent prognosis, with very few patients developing post-treatment Lyme disease syndrome. Here, we report an unusual case of Lyme disease with extremely high cerebrospinal fluid protein level and devastating neurological sequelae. The diagnosis of neuroborreliosis is based on neurological symptoms and lumbar puncture findings.