Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents.
Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis \"MYKKE.\" Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics.
From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102).
Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

UNASSIGNED: Clerodendrum petasites, an herbal plant in Thailand, has been used for many years in folk medicine. However, scientific evidence regarding CNS safety pharmacology and antinociceptive activity of C. petasites (CP) has not yet been well characterized.
UNASSIGNED: The present study aimed to assess the CNS safety pharmacology and antinociceptive and antiinflammatory effects of CP extract.
UNASSIGNED: The effect of CP extract on CNS safety pharmacology was assessed using LABORAS automated home cage monitoring and rotarod test. Its pharmacological activity was evaluated both in-vitro, and in-vivo using hot-plate, acetic acid-induced writhing, formalin, and carrageenan-induced paw edema models.
UNASSIGNED: CP extract significantly improved thermal and chemical nociceptive behaviors and acute inflammatory pain at all doses: 300, 600, and 1200 mg/kg, p.o. The antiinflammatory effect of CP extract in inflammatory pain models was comparable to the effect of positive control: indomethacin 10 mg/kg at all dose levels tested. Further, the CP extract at 600 mg/kg dose significantly inhibited 82.3% of carrageenan-induced total edema. In-vitro, CP extract at 12.5, 25, and 50 μg/mL concentrations significantly reduced the expression of LPS-induced nitric oxide, IL-6, and TNF-α expression in both RAW 264.7 macrophage and BV-2 microglial cell lines. In addition, CP extract did not show any potential effects on the CNS, indicated by no significant effects on motor coordination, spontaneous locomotor activity, general behaviors, and well-being compared to vehicle-treated mice (p > 0.05). Overall, the present study evidences the potential antinociceptive, antiinflammatory efficacies of CP extract with a favorable CNS safety profile.

UNASSIGNED: To conduct a network meta-analysis comparing all treatments for osteoarthritis (OA) pain in the Cochrane Library.
UNASSIGNED: The Cochrane Library and Epistemonikos were searched for randomized controlled trials (RCTs) about treatments for hip and knee OA. We constructed 17 broad categories, comprising drug treatments, exercise, surgery, herbs, orthotics, passive treatments, regenerative medicine, diet/weight loss, combined treatments, and controls. In addition to a full network analysis, we compared the direct/indirect effects, and studies with shorter-/longer follow-up. CINeMA software was used for assessing confidence in network meta-analysis estimates.
UNASSIGNED: We included 35 systematic reviews including 445 RCTs. There were 153 treatments for OA. In total, 491 comparisons were related to knee OA, less on hip OA, and only nine on hand OA. Six treatment categories showed clinically significant effects favoring treatment over control on pain. \"Diet/weight loss\" and \"Surgery\" had effect sizes close to zero. The network as a whole was not coherent. Of 136 treatment comparisons, none were rated as high confidence, six as moderate, 13 as low, and 117 as very low.
UNASSIGNED: Direct comparison of different available treatment options for OA is desirable, however not currently feasible in practice, due to heterogeneous study populations and lack of clear descriptions of control interventions. We found that many treatments were effective, but since the network as a whole was not coherent and lacked high confidence in the treatment comparisons, we could not produce a ranking of effects.

Postpancreatectomy hemorrhage (PPH) is a severe complication of pancreatic surgery. This condition often develops on the background of pancreatic fistula. In our report, we demonstrate an unusual case of spontaneous cessation of severe postpancreatectomy common hepatic artery (СHA) hemorrhage after distal pancreatectomy in a patient with celiac artery stenosis (CAS). A 64-year-old male diagnosed with pancreatic tail tumor underwent extended distal pancreatectomy. He developed pancreatic fistula and was discharged with an abdominal drain, and was readmitted with severe postpancreatectomy hemorrhage from a pseudoaneurysm of the CHA. The bleeding stopped spontaneously due to CHA thrombosis. The patient developed no ischemic symptoms. Spontaneous severe postpancreatectomy hemorrhage cessation is an extremely rare phenomenon. Vascular anomalies must be considered when attempting interventional radiology treatment. CHA probably may be sacrificed with no ischemic consequences in case of severe hemorrhage in patients with CAS.

UNASSIGNED: Diabetes significantly increases the risk of postoperative macular edema (PME) after cataract surgery, leading to potential worst post-operative outcomes. This study aims to compare the effect of different prophylactic interventions in improving postoperative anatomic and visual acuity outcomes of diabetes patients who underwent cataract surgery.
UNASSIGNED: We searched MEDLINE, Embase, Web of Science databases from inception until February 2nd, 2022, for studies including studies reporting PME events and/or best-corrected visual acuity (BCVA) outcomes. Random-effects Bayesian network meta-analysis was performed to compare the efficiency of intravitreal anti-vascular endothelial growth factor injections (anti-VEGF), nonsteroidal anti-inflammatory drugs (NSAIDs) and topical steroids eye drop at 1 week, 1 month, 3 months, 6 months after cataract surgery.
UNASSIGNED: The total of 2566 participants from 17 randomized controlled trials were included in the network meta-analysis, with moderate risk of bias and no evidence of publication of bias. Compared to placebo/steroid eye drop alone, patients received additional topical NSAIDs or intravitreal anti-VEGF injections had lower risk of PME at 1 month (NSAIDs: OR=0·221, 95% Confidence interval [CI], 0·044-0·755, I2 =0·0%, 5 studies; anti-VEGF: OR=0·151, 95%CI, 0·037-0·413, I2 =0·0%, 5 studies) and 3 month (NSAIDs: OR=0·370, 95%CI, 0·140-0·875, I2 =0·0%, 8 studies; anti-VEGF: OR=0·203, 95%CI, 0·101-0·353, I2 =0·0%, 4 studies) after cataract surgery. Further, additional anti-VEGF exhibited better BCVA outcome at 1 month (mean difference of LogMAR: -0·083, 95%CI, -0·17 to -0·014, I2 =62·0%, 5 studies), and 3 months (mean difference of LogMAR: -0·061, 95%CI, -0·11 to -0·011, I2 =0·0%, 5 studies) after cataract surgery. Such additional benefits did not reach statistic significant at 6 months after surgery.
UNASSIGNED: Our data suggests that compared to placebo/steroid eye drop alone, additional prophylactic anti-VEGF intervention could be considered for preventing the occurrence of PME after cataract surgery in patients with diabetes.
UNASSIGNED: Research and Development of Special (2020-1-2052); Science & Technology Project of Beijing Municipal Science & Technology Commission (Z201100005520045, Z181100001818003).

OBJECTIVE: Echinodorus macrophyllus (Kunth.) Micheli is popularly used for acute and chronic inflammatory conditions. The anti-inflammatory activity was previously demonstrated for its flavonoid-enriched fractions. The aim of this work assessed the antinociceptive properties of both aqueous extract and its fractions.
METHODS: The antinociceptive activity was determined by acetic acid-induced writhing, formalin test, tail immersion test, hot-plate test, xylene-induced ear edema methods, and the evaluation of its mechanism was performed in the writhing model. The aqueous extract of Echinodorus macrophyllus (AEEm) was fractionated, yielding Fr20, and Fr40. Fr40 composition was determined by HPLC-DAD-ESI-MS.
CONCLUSIONS: Fr20 (all doses) and Fr40 (100 mg/kg) reduced the nociception in the tail-flick model. Both fractions increased the percentage of maximum possible effect with 25 mg/kg, in the hot-plate assay, at 60 min, while AEEm reduced pain only with 50 and 100 mg/kg. There was a reduction in xylene-edema index, with Fr40 (25 mg/kg), AEEm (50 mg/kg) and Fr20 (50 mg/kg). All doses of AEEm, Fr20, and Fr40 reduced both phases of the formalin model. In the abdominal contortion model, Fr40 presented the highest activity, reducing 96% of contortions and its antinociceptive mechanism was evaluated. The results indicated the involvement of NO and adrenergic activation pathways. The main components of Fr40 are swertisin, swertiajaponin, isoorientin 7,3\'-dimethyl ether, swertisin-O-rhamnoside, isoorientin, isovitexin, isovitexin-Orhamnoside, and isovitexin-7-O-glucoside. The aqueous extract of E. macrophyllus leaves and its fractions exhibited significant analgesic effect, mediated through both peripheral and central mechanisms being considered a potentially antinociceptive drug.

UNASSIGNED: To summarize the level of knowledge regarding the effects of microcurrent therapy (MCT) on musculoskeletal pain in adults.
UNASSIGNED: The PubMed, Physiotherapy Evidence Database, Cumulative Index to Nursing Allied Health Literature, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi database were searched from the time of their inception to December 2020.
UNASSIGNED: Randomized controlled trials (RCTs) investigating the effects of MCT on musculoskeletal pain were included. Additionally, non-RCTs were included to assess the adverse events.
UNASSIGNED: The primary outcomes were pain and adverse events related to MCT. To assess the reproducibility of MCT, we evaluated the completeness of treatment description using the Template for Intervention Description and Replication (TIDieR) checklist. We also assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
UNASSIGNED: A comprehensive assessment of 4 RCTs and 5 non-RCTs that met the inclusion criteria revealed that MCT significantly improved shoulder pain (1 study, 40 patients) and knee pain (1 study, 52 patients) compared with sham MCT without any severe adverse events. MCT has clinically significant benefits for knee pain. This study also revealed a clinically significant placebo response in treating knee pain. This evidence highlights the substantial effect of placebo response in clinical care. These treatment effects on knee pain are further supported by the high quality of evidence in GRADE with high reproducibility in TIDieR.
UNASSIGNED: The findings of this meta-analysis highlight the effect of placebo response in treating knee pain. MCT is a potential, core nonpharmacologic treatment option in clinical care with minimal adverse events and should be further investigated. This study proposes a framework for the future investigation of the effect of MCT on musculoskeletal pain to enhance the study quality and reproducibility.

Bone is one of the preferential target organs of cancer metastasis. Bone metastasis is associated with various complications, of which bone pain is most common and debilitating. The cancer-associated bone pain (CABP) is induced as a consequence of increased neurogenesis, reprogramming and axonogenesis of sensory nerves (SNs) in harmony with sensitization and excitation of SNs in response to the tumor microenvironment created in bone. Importantly, CABP is associated with increased mortality, of which precise cellular and molecular mechanism remains poorly understood. Bone is densely innervated by autonomic nerves (ANs) (sympathetic and parasympathetic nerves) and SNs. Recent studies have shown that the nerves innervating the tumor microenvironment establish intimate communications with tumors, producing various stimuli for tumors to progress and disseminate. In this review, our current understanding of the role of SNs innervating bone in the pathophysiology of CABP will be overviewed. Then the hypothesis that SNs facilitate cancer progression in bone will be discussed in conjunction with our recent findings that SNs play an important role not only in the induction of CABP but also the progression of bone metastasis using a preclinical model of CABP. It is suggested that SNs are a critical component of the bone microenvironment that drives the vicious cycle between bone and cancer to progress bone metastasis. Suppression of the activity of bone-innervating SNs may have potential therapeutic effects on the progression of bone metastasis and induction of CABP.

The risk of severe coronavirus disease-2019 (COVID-19) disease seems to be higher in individuals with solid organ transplantation. Therefore, the purpose of the present research is to investigate the incidence of COVID-19 and laboratory data and epidemiologic factors in liver transplant recipients and the patients on the waiting list for liver transplantation. In this study, we evaluated the records of patients on the waiting list for liver transplantation and of recipients of a liver transplant. Demographic data, underlying disease, history of drug use and participants\' outcomes were collected. The diagnosis of SARS-CoV-2 infection for all patients was confirmed using a nasopharyngeal swab specimen with real-time RT-PCR. During the study period, 172 patients were enrolled, among whom 85 patients (49.4%) were on the waiting list for liver transplantation, and 87 patients (50.6%) were recipients of a liver transplant. Out of them, 10 (5.8%) had a positive result for SARS-CoV-2. Of these patients, 7.05% (6/85) and 4.6% (4/87) of patients on the waiting list and recipients of liver transplants were positive for SARS-CoV-2, respectively. Patients on the waiting list with COVID-19 infection had a higher median of albumin, ALT, AST, TBIL, DBIL, HDL and LDL value. In summary, the incidence of COVID-19 in liver transplant patients was slightly higher. The existence of underlying liver diseases should be well known as one of the poor predictive factors for worse outcomes in patients with COVID-19. So, comparative studies are recommended to identify risk factors for COVID-19 in patients with liver injury.

The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.