Rejected

Pain from nervous or musculoskeletal disorders is one of the most common complaints in clinical practice. Corticosteroids have a high pain-reducing effect, and their injection is generally used to control various types of pain. However, they have various adverse effects including flushing, hyperglycemia, allergic reactions, menstrual changes, immunosuppression, and adrenal suppression. Pulsed radiofrequency (PRF) is known to have a pain-reducing effect similar to that of corticosteroid injection, with nearly no major side effects. Therefore, it has been widely used to treat various types of pain, such as neuropathic, joint, discogenic, and muscle pain. In the current review, we outlined the pain-reducing mechanisms of PRF by reviewing previous studies. When PRF was first introduced, it was supposed to reduce pain by long-term depression of pain signaling from the peripheral nerve to the central nervous system. In addition, deactivation of microglia at the level of the spinal dorsal horn, reduction of proinflammatory cytokines, increased endogenous opioid precursor messenger ribonucleic acid, enhancement of noradrenergic and serotonergic descending pain inhibitory pathways, suppression of excitation of C-afferent fibers, and microscopic damage of nociceptive C- and A-delta fibers have been found to contribute to pain reduction after PRF application. However, the pain-reducing mechanism of PRF has not been clearly and definitely elucidated. Further studies are warranted to clarify the pain-reducing mechanism of PRF.

Chikungunya virus (CHIKV) infection causes intense cytokine/chemokine inflammatory responses and debilitating joint pain. Indoleamine2,3-dioxygenase 1 (IDO-1) is an enzyme that initiates the tryptophan degradation that is important in initial host innate immune defense against infectious pathogens. Besides that, IDO-1 activation acts as a regulatory mechanism to prevent overactive host immune responses. In this study, we evaluated IDO-1 activity and cytokine/chemokine patterns in CHIKV patients. Higher IDO-1 (Kyn/Trp ratio) activation was observed during the early acute phase of CHIKV infection and declined in the chronic phase. Importantly, increased concentrations of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Interferon γ (IFN-γ), C-C motif chemokine ligand 2/Monocyte Chemoattractant Protein-1 (CCL2/MCP-1) and C-X-C motif chemokine ligand 10/Interferon Protein-10 (CXCL10/IP-10) were found in the acute phase of infection, while C-C motif chemokine ligand 4/Macrophage Inflammatory Protein 1 β (CCL4/MIP-1β) was found at increased concentrations in the chronic phase. Likewise, CHIKV patients with arthritis had significantly higher concentrations of CCL4/MIP-1β compared to patients without arthritis. Taken together, these data demonstrated increased IDO-1 activity, possibly exerting both antiviral effects and regulating exacerbated inflammatory responses. CCL4/MIP-1β may have an important role in the persistent inflammation and arthritic symptoms following chikungunya infection.

Trigeminal neuralgia (TN) due to vertebrobasilar dolichoectasia (VBD) is a rare disease that can be challenging to treat. The objectives of this study are to investigate the characteristics of patients with TN due to VBD and to analyze the efficacy of microvascular decompression (MVD) by the interposition method for treatment of the condition. From 2010 until 2020, the data of 30 patients with TN due to VBD who were treated with MVD by the interposition method were analyzed retrospectively. The characteristics of the patients were compared with those of patients with non-VBD TN (n = 815). Kaplan-Meier survival analysis was performed to determine pain-free survival. The 30 patients (21 males, 9 females; mean age, 63.03 years) accounted for 3.55% of all patients with TN during the study period. In 30 patients, the offending vessel was the basilar artery (BA) in 1 patient, the vertebral artery (VA) in 6 patients, the VA plus the superior cerebellar artery (SCA) in 6 patients, the VA plus the anterior inferior cerebellar artery (AICA) in 12 patients, and the VA + SCA + AICA in 5 patients. Compared to non-VBD TN patients, those with TN due to VBD were significantly more likely to be male, to have TN of the left side, and to have hypertension (all P < 0.001). Mean age at surgery (P = 0.057) and symptom duration (P = 0.308) were comparable between the two groups. All 30 patients had immediate relief of facial pain after MVD and could stop medication. There were no postoperative complications. Over mean follow-up of 76.67 months, 3 patients had recurrence. The mean duration of pain-free survival was 70.77 months. In conclusions, TN due to VBD appears to be more likely in males, in those with hypertension, and to involve the left side. The interposition method performed by experienced and skilled neurosurgeons is a safe and effective treatment for TN due to VBD. Further studies are needed to analyze the associated long-term results and the pain recurrence rate among this special population.

Platelets may be pivotal mediators of the thrombotic and coagulopathic complications of preeclampsia (PE), linking inflammation and thrombosis with endothelial and vascular dysfunction. Both PE and gestational hypertension (GH) fall within the spectrum of hypertensive complications of pregnancy, with GH being a risk factor for preeclampsia. However, it is unclear what biomarkers distinguish PE from GH. Using a discovery size cohort, we aimed to characterize specific plasma and platelet thrombo-inflammatory drivers indicative of PE and differentiate PE from GH. We performed multiplex immunoassays, platelet and plasma quantitative proteomics and metabolomics of PE patients, comparing with non-pregnant (NP), healthy pregnant controls (PC) and GH participants. The expression pattern of plasma proteins and metabolites in PE/GH platelets was distinct from that of NP and PC. Whilst procoagulation in PC may be fibrinogen driven, inter-alpha-trypsin inhibitors ITIH2 and ITIH3 are likely mediators of thrombo-inflammation in GH and PE, and fibronectin and S100A8/9 may be major procoagulant agonists in PE only. Also enriched in PE were CCL1 and CCL27 plasma cytokines, and the platelet leucine-rich repeat-containing protein 27 and 42 (LRRC27/42), whose effects on platelets were explored using STRING analysis. Through protein-protein interactions analysis, we generated a new hypothesis for platelets' contribution to the thrombo-inflammatory states of preeclampsia.

Shortness of breath, chest pain, and palpitations occur as post-acute sequelae of COVID-19 (PASC), but whether symptoms are associated with echocardiographic abnormalities, cardiac biomarkers, or markers of systemic inflammation remains unknown. In a cross-sectional analysis, we assessed symptoms, performed echocardiograms, and measured biomarkers among adults >8 weeks after confirmed SARS-CoV-2 infection. We modeled associations between symptoms and baseline characteristics, echocardiographic findings, and biomarkers using logistic regression. We enrolled 102 participants at a median 7.2 months (IQR 4.1-9.1) following COVID-19 onset; 47 individuals reported dyspnea, chest pain, or palpitations. Median age was 52 years (range 24-86) and 41% were women. Female sex, hospitalization, IgG antibody to SARS-CoV-2 receptor binding domain and C-reactive protein were associated with symptoms. Regarding echocardiographic findings, 4/47 (9%) with symptoms had pericardial effusions compared to 0/55 without symptoms (p=0.038); those with effusions had a median 4 symptoms compared to 1 without (p<0.001). There was no strong evidence for a relationship between symptoms and echocardiographic functional parameters or other biomarkers. Among adults >8 weeks after SARS-CoV-2 infection, SARS-CoV-2 RBD antibodies, markers of inflammation and, possibly, pericardial effusions are associated with cardiopulmonary symptoms. Investigation into inflammation as a mechanism underlying PASC is warranted.

(1) Background: Treatment of cancer-related pain is still challenging, and it can be managed by both medical and interventional therapies. Spinal Cord Stimulation (SCS) is a minimally invasive technique, and its use is rapidly increasing in the treatment of chronic pain. (2) Materials and Methods: Our study aims to perform a review of the pertinent literature about current evidences in cancer pain treatment by Spinal Cord Stimulation. Moreover, we created a database based on case reports or case series (18 studies) in the literature. We analyzed a clinical group of oncological patients affected by intractable pain undergoing SCS implantation, focusing on outcome. (3) Results: The analysis of the 18 included studies in our series has shown a reduction in painful symptoms in 48 out of 56 treated patients (87.51%); also 53 out of 56 patients (96.64%) have shown an improvement in their Quality of Life (QoL). (4) Conclusions: Spinal Cord Stimulation can be considered an efficient method in the treatment of cancer-related pain. However, literature regarding SCS for the treatment of cancer-related pain is largely represented by case reports and small case series, with no effective population studies or Randomized Controlled Trials demonstrating the efficacy and the level of evidence. Further prospective studies are needed.

Cardiac troponin T (cTnT) and cTnI are considered cardiac-specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a non-cardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMD). We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in four hospitals in two countries. After cardiac work-up, patients were adjudicated into three predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed using high-sensitivity cTnT (hs-cTnT-Elecsys) and three hs-cTnI assays (hs-cTnI-Architect, hs-cTnI-Access, hs-cTnI-Vista), and compared to controls without SMD presenting with adjudicated non-cardiac chest pain to the emergency department (n=3508, mean age 55y, 37% female). In patients with available skeletal muscle biopsies, TNNT/I1-3 mRNA differential gene expression was compared to biopsies obtained in controls without SMD. Among 211 patients (mean age 57y, 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) mild and 59 (28%) severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no versus mild versus severe cardiac disease for all assays (all p<0.001). hs-cTnT-Elecsys concentrations were significantly higher in patients with SMD versus controls (median 16ng/L (IQR 7-32.5) versus 5ng/L (IQR 3-9), p<0.001) while hs-cTnI concentrations were mostly similar (hs-cTnI-Architect 2.5ng/L (IQR 1.2-6.2) versus 2.9ng/L (IQR 1.8-5.0), hs-cTnI-Access 3.3ng/L (IQR 2.4-6.1) versus 2.7ng/L (IQR 1.6-5.0) and hs-cTnI-Vista 7.4ng/L (IQR 5.2-13.4) versus 7.5ng/L (IQR 6-10)). hs-cTnT-Elecsys concentrations were above the upper-limit of normal (ULN) in 55% of patients with SMD vs 13% of controls (p<0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from non-inflammatory myopathy and myositis, showed 8-fold upregulation of TNNT2, encoding cTnT (but none for TNNI3, encoding cTnI); versus controls (n=16, pWald <0.001), the expression correlated with pathological disease activity (R=0.59, pt-statistic <0.001) and circulating hs-cTnT concentrations (R=0.26, pt-statistic =0.031). In patients with active chronic SMD, elevations in cTnT concentrations are common and not due to cardiac disease in the majority. This was not observed for cTnI, and may in part be explained by re-expression of cTnT in skeletal muscle.

Neuromodulation, also known as bioelectric neuromodulation or neurostimulation, is the therapeutic use of electrical stimulation of nerves or brain centers. Neuromodulation has been trialed in an increasing range of human diseases as well as gastrointestinal disorders. The application of neuromodulation to treat pediatric motility and functional disorders is an exciting recent development. This review aims to briefly discuss the use of neuromodulation for the treatment of pediatric gastroparesis, constipation, and visceral hyperalgesia.

Multisystem inflammatory syndrome in children (MIS-C), which is associated with coronavirus disease 2019 (COVID-19) and occurs in the immediately post-infectious period, has never-before been reported within the active duty population. It typically affects children, aged 5-13 years, but has been shown to affect those up to 20 years old. We present an 18-year-old active duty male that arrived at a military treatment facility emergency department with headache, neck pain, and shock without evidence of meningoencephalitis on cerebrospinal fluid analysis and with a negative COVID-19 test. He developed significant abdominal pain and cardiomyopathy. Chest computed tomography showed evidence of ground glass infiltrates, and repeat testing was positive for the COVID-19 virus. Multisystem inflammatory syndrome in children (MIS-C) was diagnosed and treated with a rapid improvement in the patient's condition. It is a rare but potentially fatal condition that has been shown to affect patients up to the age of 20, encompassing a large part of the junior enlisted population. Multisystem inflammatory syndrome in children (MIS-C) can lead to death, yet mimic other diseases leading to delay of care. Thus, it should be considered when faced with the appropriate constellation of symptoms.

The PRRT2 gene located at 16p11.2 encodes proline-rich transmembrane protein 2. In recent reviews, clinical spectrum caused by pathogenic PRRT2 variants is designated as PRRT2-associated paroxysmal movement disorders, which include paroxysmal kinesigenic dyskinesia, benign familial infantile epilepsy, and infantile convulsions with choreoathetosis, and hemiplegic migraine. The recurrent 16p11.2 microdeletion encompassing PRRT2 has also been reported to cause neurodevelopmental syndrome, associated with autism spectrum disorder. Although PRRT2 variants and 16p11.2 microdeletion cause each disease with the autosomal dominant manner, rare cases with bi-allelic PRRT2 variants or concurrent existence of PRRT2 variants and 16p11.2 microdeletion have been reported to show more severe phenotypes.