Rejected

There are over 80 million people currently living who have had a stroke. The ischemic injury in the brain starts a cascade of events that lead to neuronal death, inducing neurodegeneration which could lead to Alzheimer's disease (AD). Cerebrovascular diseases have been suggested to contribute to AD neuropathological changes, including brain atrophy and accumulation of abnormal proteins such as amyloid beta (Aβ). In patients older than 60 years, the incidence of dementia a year after stroke was significantly increased. Nevertheless, the molecular links between stroke and dementia are not clearly understood but could be related to neuroinflammation. Considering that activated microglia has a central role, there are brain-resident innate immune cells and are about 10-15% of glial cells in the adult brain. Their phagocytic activity is essential for synaptic homeostasis in different areas, such as the hippocampus. These cells polarize into phenotypes or subtypes: the pro-inflammatory M1 phenotype, or the immunosuppressive M2 phenotype. Phenotype M1 is induced by classical activation, where microglia secrete a high level of pro- inflammatory factors which can cause damage to the surrounding neuronal cells. Otherwise, M2 phenotype is the major effector cell with the potential to counteract pro-inflammatory reactions and promote repair genes expression. Moreover, after the classical activation, an anti-inflammatory and a repair phase are initiated to achieve tissue homeostasis. Recently it has been described the concepts of homeostatic and reactive microglia and they had been related to major AD risk, linking to a multifunctional microglial response to Aβ plaques and pathophysiology markers related, such as intracellular increased calcium. The upregulation and increased activity of purinergic receptors activated by ADP/ATP, specially P2X4R, which has a high permeability to calcium and is mainly expressed in microglial cells, is observed in diseases related to neuroinflammation, such as neuropathic pain and stroke. Thus, P2X4R is associated with microglial activation. P2X4R activation drives microglia motility via the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. Also, these receptors are involved in inflammatory-mediated prostaglandin E2 (PGE2) production and induce a secretion and increase the expression of BDNF and TNF-α which could be a link between pathologies related to aging and neuroinflammation.

Neuropathic pain (NP) is a type of intractable chronic pain with complicated etiology. The exact molecular mechanism underlying NP remains unclear. In this study, we searched for molecular biomarkers of NP.

Sickle cell disease (SCD) is an inflammatory disease that can result in both chronic and acute inflammation. Immature granulocytes (IG) are not-yet-mature white blood cells that can be easily detected in complete blood count (CBC) tests. In recent studies it has been suggested that IG may play a role in determining the prognosis of inflammatory diseases. The aim of our study was to investigate the role of IG percentage on predicting acute chest syndrome (ACS) and the severity of vaso-occlusive crisis (VOC) in patients with SCD.

Phenazopyridine is an over-the-counter urinary analgesic commonly used to alleviate the burning and urgency associated with lower urinary tract infections. Methaemoglobinaemia is an uncommon adverse effect of phenazopyridine use. We report a case of methaemoglobinaemia in a patient prescribed daily phenazopyridine to treat urethral and bladder irritation caused by a chronic indwelling Foley catheter.

Low back pain (LBP) is a common problem, but the efficacy of pharmacological therapies remains controversial. Therefore, we aimed to comprehensively evaluate and quantitatively rank various pharmacological therapies for patients with low back pain. Two meta-analyses were performed: an initial pair-wise meta-analysis, followed by network meta-analysis using a random-effects Bayesian model. We included randomized controlled trials comparing placebos, non-steroidal anti-inflammatory drugs, opioids, skeletal muscular relaxants, pregabalin (or gabapentin), and some drug combinations. The primary and secondary outcomes were pain intensity and physical function. Eighty-eight eligible trials with 21,377 patients were included. Here, we show that only skeletal muscle relaxants significantly decreased the pain intensity of acute (including subacute) low back pain. Several kinds of drugs significantly decreased the pain of chronic low back pain, but only opioids and cyclo-oxygenase 2-selective non-steroidal anti-inflammatory drugs effectively reduced pain and improved function. Pregabalin (or gabapentin) seemed to be an effective treatment to relieve pain, but it should be used with caution for low back pain.

In this case report, we review how probabilistic reasoning can be implemented in retrospect to refine the diagnostic process. A 67-year-old female with a history of polymyalgia rheumatica (PMR) and a recent dental procedure presented with weakness, falls, and chills ongoing for two weeks. She reported pain in her shoulders and lower back. On presentation, she was febrile, and labs were notable for leukocytosis with neutrophilic predominance and an elevated erythrocyte sedimentation rate (ESR). Chest radiograph revealed a left lower lung opacity, which was not seen on a repeat film. She was treated with antibiotics for community-acquired pneumonia and steroids for an exacerbation of PMR. After eight days of hospitalization, she was transferred to a subacute rehabilitation facility. A month later, she was readmitted with worsening lower back pain and right lower extremity weakness. Imaging revealed discitis and osteomyelitis at L1-L2. A spinal epidural abscess was present, leading to severe compression of the cauda equina nerve roots. Aspirate was positive for group B streptococcus. With antibiotic treatment alone, she recovered with resolution of her weakness. In reviewing the literature, it becomes evident where improvements could have been made in the diagnostic process. Fever, leukocytosis, and neurological weakness are not commonly associated with PMR exacerbations. Lack of cough or shortness of breath, a persistently elevated erythrocyte sedimentation rate and C-reactive protein despite antibiotic treatment, and a repeat chest radiograph without an opacity suggest an alternative diagnosis to pneumonia. Persistent back pain with an insidious onset is a feature of untreated spinal epidural abscess. Steroid use and dental procedures are possible risk factors for spinal epidural abscess. By shedding light on how probabilities should be estimated, we hope to encourage probabilistic thinking to improve diagnostic accuracy. As with the best political forecasters, making precise probability estimates and frequently updating them may improve diagnostic accuracy for clinicians.

Primary trigeminal neuralgia (PTN) is a clinical refractory disorder characterized by excruciating pain that severely impacts the quality of life. Several studies have shown that acupuncture can improve PTN pain. However, the comparative efficacy and safety of acupuncture are unknown. Herein, a systematic review was conducted to compare the efficacy and safety of various acupuncture methods for PTN treatment.

Chronic Urticaria (CU) is a debilitating disease whose treatment is mainly symptomatic. UCREX study aimed to identify CU patients' profile, disease management and quality-of-life (QoL) in daily clinical practice in Spain.

Intercostal nerve blockade (INB) for thoracic surgery analgesia has gained popularity in practice, but evidence demonstrating its efficacy remains sparse and inconsistent. We investigated the effect of INB with standard bupivacaine (SB) with epinephrine versus liposomal bupivacaine (LB) versus a mixed solution of the two on postoperative pain control and outcomes in video assisted thoracoscopic lobectomy patients.

Self-medication (SM) is a customary practice around the globe. Appropriate SM comes with many advantages, yet irrational SM is a concern and could lead to adverse drug events and poor health outcomes.