Rejected

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant (AD) genetic trait characterized by elevated basal serum tryptase ≥8 ng/mL, caused by increased α-tryptase-encoding copy number. HαT affects 5% to 7% of Western populations and has been associated with joint hypermobility. Hypermobility disorders are likewise frequently AD, but genetic etiologies are often elusive. Genotyping of individuals with hypermobility spectrum disorder (n = 132), hypermobile Ehlers-Danlos syndrome (n = 78), or axial skeletal abnormalities with hypermobility (n = 56) was performed. Clinical features of individuals with and without HαT were compared. When analyzing our combined cohorts, dysphagia (p = 0.007) and retained primary dentition (p = 0.0003) were significantly associated with HαT, while positive associations with anaphylaxis (p = 0.07) and pruritus (P = 0.5) did not reach significance likely due to limited sample size. Overall, HαT prevalence is not increased in individuals with hypermobility disorders, rather linked to a unique endotype, demonstrating how HαT may modify clinical presentations of complex patients.

Return to work is a challenging aspect of community integration for individuals with disabilities. The reintegration of individuals with spinal cord injury (SCI) is multifactorial; hence, regional challenges need to be investigated in the context of their clinical attributes and perceptions. A total of 121 male participants above 18 years of age with diagnosis of SCI and living at home were included in this cross-sectional survey. The study was conducted at a tertiary care rehabilitation facility in Saudi Arabia. The most common reported clinical barriers to employment were mobility, bladder incontinence, spasticity, musculoskeletal pain, and neuropathic pain. Bladder incontinence and musculoskeletal pain were the most common perceived clinical barriers for individuals with paraplegia and tetraplegia, respectively. A significant difference was observed for bowel incontinence as a reported barrier ( = 0.024) among adults less than thirty years of age in comparison with those older than thirty years. Spasticity as a barrier was reported more among patients who were older than thirty years (54.0%) compared to those younger than thirty years of age (37.9%) ( = 0.077). Twenty-two (23.7%) participants with paraplegia reported transfers as a perceived barrier to employment, which was significant ( = 0.014), and it was also reported as a significant barrier ( = 0.001) in individuals with tetraplegia (56%). This study shows that clinical conditions associated with SCI are considered potential barriers to employment by individuals with SCI. In terms of priority, the perceived barriers between individuals with tetraplegia and paraplegia were mostly different. This shows the need to consider relevant secondary health care conditions in goal setting while planning for employment in individuals with SCI.

Sarcopenia is a condition that is highly prevalent among older adults. This condition is linked to numerous adverse health outcomes, including cognitive impairment that impairs healthy ageing. While sarcopenia and cognitive impairment may share a common pathway, limited longitudinal studies exist to show the relationship between these two conditions. Therefore, this study aimed to examine the longitudinal association between sarcopenia and cognitive impairment. This is a cohort study among older adults residing in Kuala Pilah District, Negeri Sembilan, Malaysia. There were 2404 respondents at the baseline and 1946 respondents at one-year follow-up. Cognitive impairment was determined using Mini-mental State Examination scores. Sarcopenia was identified using the Asian Working Group for Sarcopenia 2019 criteria, gait speed was measured using a 4-meter gait test, handgrip strength was assessed using Jamar handheld dynamometer, and appendicular skeletal muscle mass was measured using bioelectrical impedance analysis. Generalized estimating equation (GEE) was used to determine the longitudinal association between sarcopenia and cognitive impairment, presented as relative risk (RR) and its 95% confidence interval. The prevalence of sarcopenia was 5.0% (95% CI 4.00-5.90), and severe sarcopenia was 3.60% (95% CI 2.84-4.31). Upon adjusting for covariates, older adults with sarcopenia have an 80 per cent increased risk of cognitive impairment compared to those without (RR 1.80; 95% CI 1.18-2.75). Similarly, severe sarcopenia was found to significantly increase the risk of cognitive impairment by 101 per cent in the adjusted model (RR 2.01; 95% CI 1.24-3.27). Our study showed that sarcopenia, severe sarcopenia, low physical activity, depressive symptoms, hearing impairment and chronic pain were associated with a higher risk of cognitive impairment among community-dwelling older adults. Therefore, early intervention to prevent sarcopenia, depressive symptoms, hearing impairment, chronic pain, and higher physical activity among older adults is recommended.

Osteoarthritis (OA) causes persistent pain, joint dysfunction, and physical disability. It is the most prevalent type of degenerative arthritis, affecting millions of people worldwide. OA is currently treated with a focus on pain relief, inflammation control, and artificial joint surgery. Hence, a therapeutic agent capable of preventing or delaying the progression of OA is needed. OA is strongly associated with the degeneration of the articular cartilage and changes in the ECM, which are primarily associated with a decrease in proteoglycan and collagen. In the progress of articular cartilage degradation, catabolic enzymes, such as matrix metalloproteinases (MMPs), are activated by IL-1β stimulation. Given the tight relationship between IL-1β and ECM (extra-cellular matrix) degradation, this study examined the effects of Chaenomeles Fructus (CF) on IL-1β-induced OA in rat chondrocytes. The CF treatment reduced IL-1β-induced MMP3/13 and ADAMTS-5 production at the mRNA and protein levels. Similarly, CF enhanced col2a and aggrecan accumulation and chondrocyte proliferation. CF inhibited NF-κB (nuclear factor kappa B) activation, nuclear translocation induced by IL-1β, reactive oxygen species (ROS) production, and ERK phosphorylation. CF demonstrated anti-OA and articular regeneration effects on rat chondrocytes, thus, suggesting that CF is a viable and fundamental therapeutic option for OA.

The purpose of this systematic review and network meta-analysis was to determine the analgesic effectiveness of peripheral nerve blocks (PNBs), including each anatomical approach, with or without intrathecal morphine (ITMP) in cesarean delivery (CD). All relevant randomized controlled trials comparing the analgesic effectiveness of PNBs with or without ITMP after CD until July 2021. The two co-primary outcomes were designated as (1) pain at rest 6 h after surgery and (2) postoperative cumulative 24-h morphine equivalent consumption. Secondary outcomes were the time to first analgesic request, pain at rest 24 h, and dynamic pain 6 and 24 h after surgery. Seventy-six studies (6278 women) were analyzed. The combined ilioinguinal nerve and anterior transversus abdominis plane (II-aTAP) block in conjunction with ITMP had the highest SUCRA (surface under the cumulative ranking curve) values for postoperative rest pain at 6 h (88.4%) and 24-h morphine consumption (99.4%). Additionally, ITMP, ilioinguinal-iliohypogastric nerve block in conjunction with ITMP, lateral TAP block, and wound infiltration (WI) or continuous infusion (WC) below the fascia also showed a significant reduction in two co-primary outcomes. Only the II-aTAP block had a statistically significant additional analgesic effect compared to ITMP alone on rest pain at 6 h after surgery (-7.60 (-12.49, -2.70)). In conclusion, combined II-aTAP block in conjunction with ITMP is the most effective post-cesarean analgesic strategy with lower rest pain at 6 h and cumulative 24-h morphine consumption. Using the six described analgesic strategies for postoperative pain management after CD is considered reasonable. Lateral TAP block, WI, and WC below the fascia may be useful alternatives in patients with a history of sensitivity or severe adverse effects to opioids or when the CD is conducted under general anesthesia.

We investigated the effects of multimodal combined bundle therapy, consisting of remote ischemic preconditioning (RIPC) and intrathecal morphine block (ITMB), on the early recovery of kidney function after robot-assisted laparoscopic partial nephrectomy (RALPN) in patients with renal cell carcinoma (RCC). In addition, we compared the surgical and analgesic outcomes between patients with and without bundle treatment. This prospective randomized double-blind controlled trial was performed in a cohort of 80 patients with RCC, who were divided into two groups: a bundle group ( = 40) and non-bundle group ( = 40). The primary outcome was postoperative kidney function, defined as the lowest estimated glomerular filtration rate (eGFR) on postoperative day (POD) 2. Surgical complications, pain, and length of hospital stay were assessed as secondary outcomes. The eGFR immediately after surgery was significantly lower in the bundle group compared to the preoperative baseline, but serial levels on PODs 1 and 2 and at three and six months after surgery were comparable to the preoperative baseline. The eGFR level immediately after surgery was lower in the non-bundle than bundle group, and serial levels on PODs 1 and 2 and at three months after surgery remained below the baseline. The eGFR level immediately after surgery was higher in the bundle group than in the non-bundle group. The eGFR changes immediately after surgery, and on POD 1, were smaller in the bundle than in the non-bundle group. The non-bundle group had longer hospital stays and more severe pain than the bundle group, but there were no severe surgical complications in either group. The combined RIPC and ITMB bundle may relieve ischemia-reperfusion- and pain-induced stress, as a safe and efficient means of improving renal outcomes following RALPN in patients with RCC.

The A adenosine receptor (AAR) is a target for pain, ischemia, and inflammatory disease therapy. Among the ligand tools available are selective agonists and antagonists, including radioligands, but most high-affinity non-nucleoside antagonists are limited in selectivity to primate species. We have explored the structure-activity relationship of a previously reported AAR antagonist DPTN (-[4-(3,5-dimethylphenyl)-5-(4-pyridyl)-1,3-thiazol-2-yl]nicotinamide) for radiolabeling, including 3-halo derivatives (3-iodo, MRS7907), and characterized as a high -affinity radioligand [H]MRS7799. AAR values were (nM): 0.55 (human), 3.74 (mouse), and 2.80 (rat). An extended methyl acrylate (MRS8074, ) maintained higher affinity (18.9 nM) than a 3-((5-chlorothiophen-2-yl)ethynyl) derivative . Compound had an excellent brain distribution in rats (brain/plasma ratio ∼1). Receptor docking predicted its orthosteric site binding by engaging residues that were previously found to be essential for AR binding. Thus the new radioligand promises to be a useful species-general antagonist tracer for receptor characterization and drug discovery.

Rib fracture (RF) pain management provides analgesia while reducing opioids. We postulated: (1) Prescriber factors affect opiate duration, and (2) lidocaine infusion curtails dependency.

Pain is a common postoperative complication. The ideal postoperative analgesia is awake, safe, mobile, and without side effects. The objective of this study is to provide new ideas for postoperative analgesia by observing the safety and analgesic effect of different analgesic methods in patients undergoing laparotomy after surgery.

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 10/L. Several of them also showed benefits on nasal polyps (NP), one of the most frequent comorbidities of the severe asthma, but comparative studies on their effectiveness in the association SAA-NP are currently lacking. The aim of this study is to compare the effectiveness of benralizumab, mepolizumab and omalizumab in patients with SAA-NP in real-life settings. A retrospective, observational, multicenter real-life study was realized including patients with SAA-NP treated by benralizumab, mepolizumab or omalizumab for 6 months. We analysed the nasal and respiratory symptoms, the number of asthma attacks and salbutamol use/week, acute sinusitis and severe exacerbation rates, the asthma control score, the lung function parameters, the NP endoscopic score, the sinus imaging and the blood eosinophil count 6 months before and after treatment. Seventy-two patients with SAA-NP were included: 16 treated by benralizumab, 21 by mepolizumab and 35 by omalizumab. After 6 months of treatment, almost all studied parameters were improved (except sinus imaging) with a greater effect of omalizumab on the nasal pruritus (p = 0.001) and more benefits of benralizumab on exacerbations rate, asthma attacks per week and lung function (all p < 0.05). Benralizumab and mepolizumab were more effective to improve the NP endoscopic score and the blood eosinophil count (both p < 0.001). All three biological therapies showed effectiveness by improving asthma and nasal outcomes in patients with SAA-NP. Several differences have been found that should be confirmed by larger comparative studies.