Rejected

Knee osteoarthritis (KOA) is a high incidence chronic joint disease that seriously affects patients' quality of life, and current treatment methods have limited efficacy. Self-management may be an effective strategy for KOA, and clinicians have been showing increased interest recently. However, the effectiveness of self-management for KOA remains controversial.

Unexplained persistent perineal pain poses a differential diagnosis, including pelvic nerve lesions. The rare occurrence of pelvic schwannoma is easily shown by a MRI as a T2-hyperintense enhancing mass.

We systematically analyzed the mechanism of plant-derived drugs alleviating cancer pain in our hospital through network pharmacology, so as to provide the possibility of further application of traditional Chinese medicine in the treatment of cancer pain.

Japanese encephalitis (JE) is an acute viral central nervous system disease, although less than 1% of patients infected with Japanese encephalitis virus (JEV) result in JE, which has an extremely poor prognosis. The Routine detection methods for JEV are time-consuming or limited by hospital conditions, therefore, need the quicker and sensitive techniques to detect JEV. Here, we reported a 14-year-old female who was admitted to our hospital with a severe fever, progressively headache and unconsciousness. Based on the clinical presentation, Preliminary diagnosis on admission indicated central nervous system infection of suspected viral meningoencephalitis or autoimmune encephalitis. The patient's symptoms were unrelieved after being treated with empiric antiviral therapy. Magnetic resonance imaging (MRI) showed that the lesions were located in the bilateral thalamus, head of caudate nucleus, and right lenticular nucleus, so we had to consider the possibility of Flaviviruses infection. We sent the cerebrospinal fluid (CSF) for metagenomic next-generation sequencing (mNGS) immediately, subsequent result suggested the infection caused by JEV. Two days later the results of the serum agglutination test confirmed that virus immunoglobulin M antibody positive. After a week treatment with intravenous immunoglobulin (IVIG), meanwhile, the lumbar puncture was used to check the pressure and various indicators of the CSF again to evaluate the treatment effect, An decrease in the number of WBC indicates, protein and unique RNA reads that the previous experimental treatment was effective, accompany by temperature and consciousness of the patient was normalized. Two weeks after admission, the patient was transferred to the rehabilitation hospital, MR showed the lesions had disappeared completely after 2 months of follow-up. We believed that mNGS may be an effective method for rapid identification of JE.

Pembrolizumab is an immune checkpoint inhibitor being increasingly used as immunotherapy for a multitude of cancers. With the increasing use of these agents, various immune-related adverse events are being recognized. Lichenoid reaction, pruritus, and eczema are well-established cutaneous side effects of pembrolizumab, but bullous pemphigoid (BP) is a rare side effect of the drug. It is difficult to establish this diagnosis because it needs a detailed history of the timeline of the evolution of symptoms and careful ruling out of other etiologies, especially other drugs. Here, we present the case of a 66-year-old male who developed BP after receiving pembrolizumab therapy for non-small-cell lung cancer. Discontinuation of pembrolizumab and the use of topical and systemic steroids led to the complete resolution of symptoms. Physicians should be aware of this potential complication and keep it on their differential diagnosis when treating patients on immune checkpoint inhibitors.

Spinal cord injury (SCI) can cause paralysis and serious chronic morbidity, and there is no effective treatment. Based on our previous experimental results of spinal cord fusion (SCF) in mice, rats, beagles, and monkeys, we developed a surgical protocol of SCF for paraplegic human patients. We designed a novel surgical procedure of SCF, called sural nerve transplantation (SNT), for human patients with lower thoracic SCI and distal cord dysfunction.

The precipitous and medically contraindicated reduction or "tapering" of opioids for patients with chronic pain due to serious medical conditions has caused needless suffering and, increasingly, suicide. Physicians could be liable for wrongful death based on negligent tapering of opioids.

Chronic inflammatory pain seriously affects patients' quality of life because of a paucity of effective clinical treatments caused, at least in part, by lack of full understanding of the underlying mechanisms. miRNAs are known to be involved in inflammatory pain via silencing or degrading of target mRNA in the cytoplasm. The present study provides a novel mechanism by which miRNA-22 positively regulates metal-regulatory transcription factor 1 () in the nuclei of neurons in the dorsal horn of the spinal cord. We found that miRNA-22 was significantly increased in the dorsal horn of mice with either inflammatory pain induced by plantar injection of complete Freund's adjuvant (CFA) or neuropathic pain induced by unilateral sciatic nerve chronic constrictive injury (CCI). Knocking down or blocking miRNA-22 alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas overexpressing miRNA-22 produced pain-like behaviors. Mechanistically, the increased miRNA-22 binds directly to the promoter to recruit RNA polymerase II and elevate expression. The increased subsequently enhances spinal central sensitization, as evidenced by increased expression of p-ERK1/2, GFAP, and c-Fos in the dorsal horn. Our findings suggest that the miRNA-22- signaling axis in the dorsal horn plays a critical role in the induction and maintenance of inflammatory pain. This signaling pathway may be a promising therapeutic target in inflammatory pain.

Enriched enrollment randomized withdrawal (EERW) pain trials are designed to include only responders with considerable pain relief without unacceptable side effects into the randomized phase. There are no recommendations for primary endpoints in such trials. Our objective was to propose recommendations based on assessment of trial characteristics, endpoints and effect sizes in EERW pain trials. We conducted a systematic review by searching electronic databases up to June 2020 for EERW trials comparing an analgesic with a placebo in adults suffering from chronic pain. A total of 28 trials met our criteria, involving 13662 patients in the open or single-blind phase and 7937 patients in the double-blind phase. As primary endpoint 18 trials used pain intensity measured with the visual analogue scale (VAS) or the 11-point numerical rating scale (NRS); 1 trial used a 4-point NRS. Loss of therapeutic response (LTR) was used in 1 trial and time to LTR was used in 8 trials as primary endpoint. Definitions of time to LTR differed considerably between trials. Only 2 out of 8 trials using time to LTR as primary endpoint reported the percentage of patients experiencing a minimum pain relief of 50%, compared to 14 out of 18 trials using NRS or VAS. Due to the complexity and diversity of time to LTR in EERW pain trials, we propose to use the NRS as primary endpoint with conservative imputation methods, and to use time to LTR as secondary endpoint.

Mesenteric ischemia (MI) is a condition characterized by compromised intestinal perfusion, leading to varied patterns of bowel hypoxia that requires prompt diagnosis and surgical intervention. Here, we report a case in which indocyanine green (ICG) was utilized to evaluate intestinal blood flow in a patient with acute-on-chronic MI. A 65-year-old underweight female presented with abdominal pain out of proportion to exam and was found to have diffuse aortic atherosclerotic disease with chronic occlusion of both superior and inferior mesenteric arteries with distal reconstitution. After multidisciplinary evaluation, elective treatment with vascular surgery was planned; however, on day three of her hospitalization, the patient's abdominal pain acutely worsened. She was taken to the OR for exploratory laparotomy. Under white light, the small bowel from the ligament of Treitz (LOT) to the terminal ileum and the large bowel from the cecum to the splenic flexure appeared ischemic with patchy areas of necrosis. Fluorescence angiography was then performed; injection of indocyanine green (ICG) dye and imaging with the SPY-PHI near-infrared camera system demonstrated appropriate blood flow into the bowel mesentery, with complete absence of flow into the bowel mucosal surface from the LOT to the splenic flexure, confirming irreversible bowel necrosis. Introduction of ICG intraoperatively decreased the uncertainty associated with white light assessment of bowel viability, leading to a definitive intraoperative diagnosis and clear plan of care. The use of fluorescence guidance to diagnose fulminant small and large bowel necrosis prevented the surgical team from having to perform multiple takebacks to the operating room in the setting of a nonsurvivable injury. Had the surgical team relied on the white light appearance of the bowel, they would not have been able to diagnose the true extent of bowel demise. The patient was placed on comfort care for this devastating nonsurvivable injury.