YokoCo

Chronic-pain is a debilitating illness that has become exceedingly widespread with currently limited treatments. Differences in the molecular signature of nociceptors, have been demonstrated between human and the commonly-used mouse model, suggesting functional differences in detection and transmission of noxious-stimuli. Therefore, direct understanding of pain-physiology in humans is required for pain treatment. This could be facilitated by studying humans carrying deleterious genetic mutations affecting pain sensation. The transient receptor potential vanilloid 1 (TRPV1) channel is associated with several body-functions, in particular, noxious-heat detection and inflammatory-pain. Reports of adverse effects in human trials have hinder the clinical development of TRPV1 antagonists as novel pain relievers. Hence, studies on the functional roles of TRPV1, which currently rely mainly on evidences obtained from rodents, should be extended to humans. Here, we examined humans carrying a unique missense mutation in TRPV1, rendering the channel non-functional. The affected individual demonstrated lack of aversion towards capsaicin and elevated heat-pain threshold. Surprisingly, he showed elevated cold-pain threshold and extensive neurogenic inflammatory flare and pain-responses following application of the TRPA1 channel-activator, mustard-oil. Our study provides the first direct evidence for pain-related functional-changes linked to TRPV1 in humans, which is a prime target in the development of novel pain-relievers.

Spinal cord stimulator (SCS) is approved to treat various pain conditions and is commonly seen in the chronic pain patient population. Due to the nature of the device and its location, infections associated with SCS have a particularly high morbidity. According to post-market data and medical device reports, 87% of patients receiving SCS implants were given perioperative antibiotics as the implantable neurostimulator or receiver pocket serve as the most common sites of infection. The most common antibiotics for surgical prophylaxis given are first-generation cephalosporins (cefalexin, cefazolin) at the time of implantation. If deep infection is suspected, imaging in the form of CT scan should be obtained as physical exam is not always sufficient. For infections involving the epidural space, vertebra, or intervertebral discs, MRI is the preferred imaging modality. If meningitis is suspected, a lumbar puncture is recommended. Positive cultures can help guide antibiotic therapy.

The main objective of this study is to examine chronic pain and limping in relation to lower extremity and pelvic fracture location in addition to fracture combinations if multiple fractures are present on the same leg that have not been previously reported. We hypothesize that fracture pattern and location of lower extremity and pelvis fractures of multiple injured patients influence their long-term pain outcome.

Psoriasis is a chronic, immune-mediated, skin disease with a significantly negative impact on patients' quality of life. Moderate-to-severe disease often requires systemic therapies and currently available ones still have numerous disadvantages or limitations. Tyrosine kinase 2 (TYK2) mediates immune signaling of IL-12, IL-23, and type I interferons, without interfering with other critical systemic functions. This article aims to review the current knowledge on deucravacitinib, a new oral drug which selectively inhibits TYK2, granting it a low risk of off-target effects. Two phase 3, 52-week trials evaluated deucravacitinib 6 mg against placebo and apremilast – POETYK PSO-1 and PSO-2 -, enrolling 1688 patients with moderate-to-severe psoriasis. At week 16, over 50% of patients treated with deucravacitinib reached PASI75, significantly superior to placebo and apremilast. Symptomatic improvement was also reported, with greater impact on itch. Deucravacitinib was well tolerated and safe. There were no reports of serious infections, thromboembolic events, or laboratory abnormalities. Persistent efficacy and consistent safety profiles were reported for up to 2 years. Deucravacitinib has the potential to become a safe, effective, and well-tolerated treatment for patients with moderate-to-severe disease. Future studies will be important to determine the exact role of this drug in the treatment of psoriasis.

The reciprocal interaction between pain and negative affect is acknowledged but pain-related alterations in brain circuits involved in this interaction, such as the mediodorsal thalamus (MDThal), still require a better understanding. We sought to investigate the relationship between MDThal circuitry, negative affect and pain severity in chronic musculoskeletal pain. For these analyses, participants with chronic knee pain (CKP, n=74) and without (n=36) completed magnetic resonance imaging scans and questionnaires. Seed-based MDThal functional connectivity (FC) was compared between groups. Within CKP group, we assessed the interdependence of MDThal FC with negative affect. Finally, post-hoc moderation analysis explored whether burden of pain influences affect-related MDThal FC. The CKP group showed altered MDThal FC to hippocampus, ventromedial prefrontal cortex, and subgenual anterior cingulate. Furthermore, in CKP group, MDThal connectivity correlated significantly with negative affect in several brain regions, most notably the medial prefrontal cortex, and this association was stronger with increasing pain burden and absent in pain-free controls. In conclusion, we demonstrate mediodorsal thalamo-cortical dysconnectivity in chronic pain with areas linked to mood disorders and associations of MDThal FC with negative affect. Moreover, burden of pain seems to enhance affect sensitivity of MDThal FC. These findings suggest mediodorsal thalamic network changes as possible drivers of the detrimental interplay between chronic pain and negative affect.

Saussurea involucrata oral liquid (SIOL) can clinically relieve symptoms, such as joint pain and swelling, and morning stiffness, in patients with rheumatoid arthritis (RA). However, the mechanism of action remains unclear. This study used a combination of gut microbiota and serum metabolomics analysis to investigate the effects and potential mechanisms of SIOL intervention on rats with RA induced by type II bovine collagen and Freund's complete adjuvant. Results showed that SIOL treatment consequently improved the degree of ankle joint swelling, joint histopathological changes, joint pathological score, and expression of serum-related inflammatory cytokines (interleukin (IL)-1β, IL-4, IL-6, IL-10, and tumor necrosis factor-α) in RA model rats. 16 S rRNA sequencing results showed that SIOL increased the relative richness of the Lactobacillus and Bacteroides genus and decreased the relative richness of Romboutsia, Alloprevotella, Blautia, and Helicobacter genus. Serum nontargeted metabolomic results indicated that SIOL could regulate metabolites related to metabolic pathways, such as glycine, serine, threonine, galactose, cysteine, and methionine metabolism. Spearman correlation analysis showed that the regulatory effects of SIOL on the tricarboxylic acid (TCA) cycle, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism pathways were correlated with changes in the richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus in the gut microbiome. In conclusion, this study revealed the ameliorative effects of SIOL on RA and suggested that the therapeutic effects of SIOL on RA may be related to the regulation of the community richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus, thereby improving the TCA cycle; phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism-related pathways.

Porokeratosis ptychotropica represents an unusual form of porokeratosis characterized by symmetrical dyskeratotic skin lesions on the gluteal clefts. Herein, we report a case of porokeratosis ptychotropica.

The aim of this randomized double-blind placebo controlled clinical trial was to investigate the effects of different doses of esketamine combined with sufentanil for postoperative intravenous controlled analgesia after cesarean section and the incidence of postpartum depression.

The effect of intraoperative tidal volume (VT) on clinical outcomes after off-pump coronary artery bypass grafting (OPCAB) has not been studied. The aim of this study was to assess the relationship between intraoperative tidal volume (VT) and acute kidney injury (AKI ) after OPCAB. A total of 1049 patients who underwent OPCAB between January 2009 and December 2018 were analyzed. Patients were divided into high (>8 ml/kg) and low VT (≤8 ml/kg) groups (intraoperative median VT standardized to predicted body weight). The data were fitted using a multivariable logistic regression model. Subgroup analyses were performed according to age, sex, comorbidities, preoperative laboratory variables, operative profiles, and Cleveland score. The risk of AKI was not significantly higher in the high than the low VT group (OR: 1.15, 95% CI: 0.80-1.66; P = .459); however, subgroup analyses revealed that a high VT may increase the risk of AKI in males, patients aged < 70 years, with chronic kidney disease, a left ventricular ejection fraction < 35%, or a long duration of surgery. High intraoperative VTs were not associated with an increased risk of AKI after OPCAB. Nonetheless, it may increase the risk of AKI in certain subgroups, such as younger age, male sex, reduced renal and cardiac function, and a long surgery time.