Rejected

Spartalizumab is a humanized IgG4κ monoclonal antibody that binds programmed death-1 (PD-1) and blocks its interaction with PD-L1 and PD-L2. This phase 1/2 study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of spartalizumab in patients with advanced or metastatic solid tumors.

Tension-type headache (TTH) is the most prevalent primary headache type world-wide. Chronic TTH (CTTH) of >15 headache-affected days per month for > 3 months can cause considerable pain and disability.

Osteoarthritis is the leading cause of chronic knee pain (CKP) in older adults. Medical practitioners often manage CKP using both pharmacological and nonpharmacological therapies. However, no studies have specifically focused on extracorporeal shockwave therapy (ESWT) for treatment of CKP.

Melanoma is one of the most aggressive and less chemotherapy-responsive human cancers, representing a major public health issue worldwide. The early diagnosis still represents the best approach in order to reduce mortality, especially in advanced stages. Preclinical evidence, collected through several in vitro and in vivo models, has been accumulating about the pathophysiological involvement of β-adrenoceptors in melanoma progression. This involvement has been paralleled by the evidence that drugs blocking β-adrenoceptors (β-blockers) may have a relevant role in the treatment of melanoma and in the prevention of its progression. β-blockers are a class of drugs extensively used in clinical practice, not limited to cardiovascular therapeutics. Evidence collected through retrospective and prospective observational studies suggests that treatment with β-blockers, mainly propranolol, is able to delay melanoma progression. Although conclusive evidence is still lacking, current knowledge proposes β-blockers as an opportunity for antitumor treatment in melanoma. Clinical trials are needed in order to prove their claimed efficacy. Graphical Abstract.

Diclofenac potassium for oral solution (CAMBIA®) may be an alternative for patients who would otherwise need to be seen in a healthcare setting for parenteral ketorolac. CAMBIA® is FDA-approved for the abortive treatment of migraine and has demonstrated superiority over generic diclofenac tablets with rapid migraine reduction. This study assessed for efficacy of CAMBIA® as an alternative outpatient treatment for refractory migraine to parenteral ketorolac.

Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.

Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the family Togaviridae and genus Alphavirus, that causes an acute febrile illness, chikungunya fever, transmitted to humans by Aedes species mosquitoes. During acute illness, patients have high fever, polyarthralgias/polyarthritis, maculopapular rash, headache, and myalgia that lasts for days to weeks. Following resolution of acute infection, a significant proportion of patients develop chronic chikungunya arthritis that can resemble rheumatoid arthritis. In this review, we first consider the historical background of infectious causes of inflammatory arthritis, and then the pathogenic and clinical manifestations of chronic chikungunya arthritis as an rheumatoid arthritis mimic. We believe that chronic chikungunya arthritis may be a post-infectious, inflammatory process and that an understanding of the parallels and differences between chronic chikungunya arthritis and rheumatoid arthritis may offer insights into better diagnosis and treatment of both diseases.

Neck pain is the fourth leading cause of disability. Acute neck pain largely resolves within 2 months. History and physical examination play a key role in ruling out some of the more serious causes for neck pain. The evidence for pharmacologic interventions for acute and chronic musculoskeletal neck pain is limited. Lower back pain is the leading cause of disability and productivity loss. Consultation with a physical medicine and rehabilitation spine specialist within 48 hours for acute pain and within 10 days for all patients with lower back pain may significantly decrease rate of surgical interventions and increase patient satisfaction.

To evaluate the analgesic effects of orally administered gabapentin on horses with chronic thoracic limb lameness.

Ketogenic diet (KD), the "High-fat, low-carbohydrate, adequate-protein" diet strategy, replacing glucose with ketone bodies, is effective against several diseases, from intractable epileptic seizures, metabolic disorders, tumors, autosomal dominant polycystic kidney disease, and neurodegeneration to skeletal muscle atrophy and peripheral neuropathy. Key mechanisms include augmented mitochondrial efficiency, reduced oxidative stress, and regulated phospho-AMP-activated protein kinase, gamma-aminobutyric acid-glutamate, Na K pump, leptin and adiponectin levels, ghrelin levels, lipogenesis, ketogenesis, lipolysis, and gluconeogenesis. In cancer cells, KD targets glucose metabolism, suppresses insulin-like growth factor-1 and PI3K/AKT/mTOR pathways, and reduces cancer cachexia and muscle waste and fatigue. An associated increased skeletal proliferator-activated receptor-γ coactivator-1α activity alters systemic ketone body homeostasis, contributing toward attenuated diabetic hyperketonemia. Antioxidative and anti-inflammatory properties enable KD enhance endurance and sports performances while preventing exercise-induced muscle and organ debility. KD reduces metabolic syndromes-associated allodynia and promotes peripheral axonal and sensory regeneration. This review enlightens effects of KD on various disease conditions. PRACTICAL APPLICATIONS: It is increasingly being realized that diet plays a very important role in our fight against several diseases. This can range from neurological disorders to diabetes and cancer. In this context, the potential of KD, the "High-fat, low-carbohydrate, adequate-protein" diet strategy, is increasingly being realized. In this article, we provide a comprehensive analysis of the benefits of KD against many diseases and discuss the underlying biochemical mechanisms. We hope that our write-up will stimulate further research on KD and help generate an interest for the populations to adopt this healthy diet. It can help overcome the problems associated with weight and dysregulated metabolism.