Rejected

A 60-year-old woman with diabetes mellitus presented to the emergency department (ER) with complaints of lower limb weakness, preceded by diarrhea. She complained of sweating and palpitations. There was no fever, cough, trauma, seizures, or headache. There was global weakness in all four limbs with absent reflexes and hypotonia. Examination of cranial nerves, the sensory system, and other systems was normal. Guillain-Barre syndrome (GBS) was suspected, but due to the patient's co-morbidities, treatment was withheld for 24 hours and the patient was kept under observation. Medical consultation was sought and thyroid function tests were ordered which showed thyroid-stimulating hormone (TSH) 0.019 uIU/ml (normal: 0.35-4.94 uIU/ml), free triiodothyronine (T3) 11.94 pg/ml (normal: 2.0-4.4 pg/ml), and free thyroxine (T4) >5 ng/dl (normal: 0.70-1.48 ng/dl). Thyroid storm was suspected and she was treated with hydrocortisone, propylthiouracil, Lugol iodine, and beta-blocker and her symptoms improved in 10 days with resolution of the weakness, confirming the diagnosis. Besides highlighting this association, this report demonstrates the importance of conducting thyroid function tests in patients presenting with axonal neuropathy. In patients having weakness in all four limbs and presenting with multiple comorbidities, we need to exclude medical reasons before starting treatment for GBS, such as in our case where it was thyrotoxicosis.

Cellular senescence is a contributor to intervertebral disc (IVD) degeneration and low back pain. Here, we found that RG-7112, a potent mouse double-minute two protein inhibitor, selectively kills senescent IVD cells through apoptosis. Gene expression pathway analysis was used to compare the functional networks of genes affected by RG-7112, a pure synthetic senolytic with o-Vanillin a natural and anti-inflammatory senolytic. Both affected a functional gene network related to cell death and survival. O-Vanillin also affected networks related to cell cycle progression as well as connective tissue development and function. Both senolytics effectively decreased the senescence-associated secretory phenotype (SASP) of IVD cells. Furthermore, bioavailability and efficacy were verified ex vivo in the physiological environment of degenerating intact human discs where a single dose improved disc matrix homeostasis. Matrix improvement correlated with a reduction in senescent cells and SASP, supporting a translational potential of targeting senescent cells as a therapeutic intervention.

New monoclonal antibodies against the calcitonin generelated peptide pathway have recently been developed for the  prevention of migraine. The aim of this study is to compare the efficacy  of monoclonal antibodies against the calcitonin generelated peptide  pathway drugs in chronic migraine through an adjusted indirect  treatment comparison, and to establish whether they can be considered  equivalent therapeutic alternatives in this pathology.

Many experimental and clinical studies have proven that the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tropism to the nervous system. The infection of the nervous system by SARS-CoV-2 can occur via the nasal route through trans-synaptic pathways. Coronaviruses can infect neurons and glial cells through angiotensin-converting enzyme 2 (ACE2) receptors or by endocytosis. The infection of the central nervous system (CNS) with the systemic inflammation associated with Coronavirus Disease 2019 (COVID-19) leads to the impairment of the blood-brain barrier and triggers a neuroinflammatory response with reactive astrogliosis, and microglial activation. In addition, brain stem cells are damaged, which results in respiratory distress. Apart from typical symptoms of COVID-19 related to the involvement of the respiratory system, neurological manifestations such as headache, dizziness, myalgia, anosmia, ageusia, encephalopathy, encephalitis, stroke, epileptic seizures, rhabdomyolysis and the Guillain-Barre syndrome (GBS) are associated with SARS-CoV-2 infection. In the study, attention was paid to the currently known neurological manifestations of COVID-19 so that they could be considered mainly in COVID-19 asymptomatic patients, which may limit the transmission of coronavirus infection.

To report complications after arthroscopic rotator cuff repairs (ARCRs) from a large patient cohort based on clinical application of a newly-defined core event set (CES) and severity grading.

Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared.

Degradation of extracellular matrix (ECM) in intervertebral disks (IVDs) during IVD degeneration plays a vital role in low back pain (LBP). In healthy IVDs, synthesis and degradation of ECM are kept in balance by matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs. MMPs are enzymes responsible for ECM degradation, and their expression levels are known to increase in degenerated disks. However, the exact pathophysiological concentration of MMP-1 in the degenerated disks of patients with chronic LBP has not been reported previously. Factors secreted by human mesenchymal stem cells (hMSCs) have shown positive results in cell therapy of degenerated disks. The aim of this study was to investigate the pathophysiological MMP-1 concentration (in ng/mL) in degenerated disk tissue and to evaluate if conditioned media (CM) from hMSCs could mitigate the effects of MMP-1 at the detected levels in a 3D in vitro disk cell (DC) pellet model. Tissue levels of MMP-1 were quantified in disk tissue collected from 6 chronic LBP patients undergoing surgery. DC pellet cultures were performed to investigate the effects of MMP-1 alone and the effects of conditioned media (CM) in the presence of MMP-1. MMP-1 was introduced in the pellets on day 14 at concentrations of 5, 50, or 100 ng/mL. The pellets were harvested on day 28 and evaluated for cell viability, proliferation, and ECM production. The mean concentration of MMP-1 in disk tissue was 151 ng/mL. Results from pellet cultures demonstrated a higher number of viable cells, glycosaminoglycan production, and ECM accumulation in the CM group even in the presence of MMP-1 compared to the controls. However, the level decreased with increasing MMP-1 concentration. The results demonstrated that CM has the ability to mitigate matrix degradation property of MMP-1 up to 50 ng/mL suggesting that CM could potentially be used to treat early stages of disk degeneration.

In this study, we aimed to evaluate the effect of gender on clinical findings, disease activity, functional status and quality of life in patients with axial involvement in Turkey. Patients with PsA who met the CASPAR classification criteria were enrolled consequently in this cohort. Turkish League Against Rheumatism (TLAR)-Network was formed with the participation of 25 centres. The demographic variables, fatigue, diagnostic delay, the beginning of peripheral arthritis, enthesitis, dactylitis and spine involvement, inflammatory low back pain, BASFI, HAQ, HAQ-s, visual analog scale-pain (VAS-pain), anxiety, depression and disease activity parameters (ESR, DAS28, BASDAI) were recorded. Axial involvement was assessed according to clinical and radiological data according to modified New York (MNYC) or SpondyloArthritis International Society Assessment (ASAS) criteria (AC). A total of 1018 patients with PsA were included in this study. Of the 373 patients with axial involvement, 150 were male (40.2%) and 223 (59.8%) were female. Spondylitis was detected in 14,7% of men and 21,9% of women in all patients. Pain score (VAS) (p< 0,002), fatigue (p <0.001), ESR (p <0.001), DAS28 (p <0.001), BASDAI score (p <0.001), PsAQoL (p <0.001), HAQ score (p < 0,01), HAQ-S score (p< 0.001), anxiety (p <0.001), depression (p < 0,024), FACIT (p <0.001) and FiRST (p <0.001) scores were statistically significantly worse in women than males with axial PsA. However, quality of life was better (p <0.001) and PASI score (p< 0.005) were statistically worse in male patients than in female patients with axial involvement. This study has shown that the burden of disease in axial PsA has significant difference between genders. Disease activity, physical disability, functional limitation, depression and anxiety scores were higher in female patients, while quality of life were better and PASI score were higher in male patients. Therefore, we suggest that new strategies should be developed for more effective treatment of axial PsA in female patients.

Opioid use disorder (OUD), a leading cause of morbidity and mortality in the USA, can be effectively treated with buprenorphine. However, the same pharmacologic properties (e.g., high affinity, partial agonism, long half-life) that make it ideal as a treatment for OUD often cause concern among clinicians that buprenorphine will prevent effective management of acute pain with full agonist opioid analgesics. Because of this concern, many patients are asked to stop buprenorphine preoperatively or at the onset of acute pain, placing them at high risk for both relapse and a difficult transition back to buprenorphine after acute pain has resolved. The purpose of this review is to summarize the existing literature for acute pain and perioperative management in patients treated with buprenorphine for OUD and to provide practical management recommendations for generalist practitioners based on evidence and clinical experience. In short, evidence suggests that sufficient analgesia can be achieved with maintenance of buprenorphine and use of both opioid and non-opioid analgesic options for breakthrough pain. We recommend that clinicians (1) continue buprenorphine in the perioperative or acute pain period for patients with OUD; (2) use a multi-modal analgesic approach; (3) pay attention to care coordination and discharge planning when making an analgesic plan for patients with OUD treated with buprenorphine; and (4) use an individualized approach founded upon shared decision-making. Clinical examples involving mild and severe pain are discussed to highlight important management principles.

We report six adult patients with Tyrosinaemia type 1 (HT-1) who presented with recurrent porphyria-like neurological crises after discontinuation/interruption of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC) treatment. The crises were life-threatening for some of the patients, with respiratory muscle paralysis requiring ventilatory support, hemodynamic disturbance due to autonomic changes requiring resuscitation, acute progressive ascending motor neuropathy causing profound impairment, recurrent seizures, and neuropathic pain. Our patients' porphyria-like presentations were variably misdiagnosed, with delay to diagnosis resulting in more severe recurrent attacks. We report the first series of neurological crises in adult patients with HT-1. These crises, which may be fatal, can be prevented and treated effectively with neurologist/physician awareness and patient education.