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Locoregional interventional therapy including transcatheter arterial chemoembolization (TACE) and ablation are the current standard of treatment for early-to-mid-stage hepatocellular carcinoma (HCC). However, questions remain unanswered regarding the management of recurrence after locoregional treatment. PD-1 inhibitors can block inhibitory signals of T-cell activation and proliferation to reduce the recurrence. We conducted a single-arm phase 2 trial to evaluate the efficacy and safety of PD-1 inhibitors following locoregional interventional therapy in HCC patients with high recurrence risk guided by our novel scoring system.

We report a rare case of a patient with cystic fibrosis suffering from debilitating abdominal pain due to chronic pancreatitis. This 13-year-old patient was evaluated for surgical intervention to relieve pain from chronic pancreatitis and to improve quality of life. The patient carried two mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; the most common ΔF508 variant and a second variant, p.Glu1044Gly, which has not been previously described. The patient's condition did not improve despite medical management and multiple endoscopic interventions, and therefore total pancreatectomy with islet autotransplantation and a near-total duodenectomy was offered for definitive management. Patient-derived duodenal crypts were isolated and cultured from the resected duodenum, and duodenal organoids were generated to test CFTR function. Our studies demonstrate that this novel mutation (ΔF508/p.Glu1044Gly) caused severely impaired CFTR function . The Food and Drug Administration (FDA)-approved drug ivacaftor, a CFTR potentiator, was identified to robustly improve CFTR function in the context of this novel mutation. Herein, we describe a personalized medicine approach consisting of performing drug testing on individual patient derived organoids that has potential to guide management of patients with novel CFTR genetic mutations. Identified effective medical therapeutics using this approach may avoid irreversible surgical treatments such as total pancreatectomy with islet autotransplantation in the future.

Orofacial pain, in particular, chronic orofacial pain remains a great challenge in clinical practice. To better understand the underlying mechanism of disease, it is essential to apply a feasible and stable preclinical measurement of facial pain. Here, we introduced a novel electrical noxious stimulator in freely behavioral rodents and examined its validation in both naïve and chronic orofacial pain animals.

Pruritus of chronic spontaneous urticaria (CSU) is one of the most common and irritating sensations that severely affects the quality of life. However, the changes in the functional connectivity (FC) between thalamic subregions and other brain regions have not been fully elucidated. This study aimed to explore the potential changes in brain neural circuits by focusing on various subregions of the thalamus in patients with CSU pruritus to contribute to the understanding of chronic pruritus from the perspective of central mechanisms. A total of 56 patients with CSU and 30 healthy controls (HCs) completed the data analysis. Urticaria Activity Score 7 (UAS7), pruritus visual analog score (VAS-P), Dermatological Life Quality Index (DLQI), and immunoglobulin E (IgE) values were collected to assess clinical symptoms. Seed-based resting-state functional connectivity (rs-FC) analysis was used to assess relevant changes in the neural circuits of the brain. Compared to HCs, seeds within the caudal temporal thalamus (cTtha) on the right side of patients with CSU showed increased rs-FC with the cerebellum anterior lobe (CAL). Seeds within the lateral prefrontal thalamus (lPFtha) on the right side showed increased rs-FC with both CAL and pons, while those within the medial prefrontal thalamus (mPFtha) on the right side showed increased rs-FC with both CAL and the dorsal lateral prefrontal cortex (dlPFC) on the right side. Seeds within the posterior parietal thalamus (PPtha) on the right side showed increased rs-FC with the cerebellum posterior lobe (CPL) on the left side. The UAS7 values and IgE levels were positively correlated with the rs-FC of the right dlPFC. Our results suggest that patients with CSU may exhibit stronger rs-FC alterations between certain thalamic subregions and other brain regions. These changes affect areas of the brain involved in sensorimotor and scratching.

Cerebrovascular involvement of Kawasaki disease (KD) is poorly studied. White matter hyperintensities (WMH) indicate cerebral small vessel disease and increase the risk for stroke.

A wide variety of conditions can cause trigeminal neuralgia (TN).

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA. To investigate the effect of live LA-1 on OA progression, we administered LA-1 into monosodium iodoacetate (MIA)-induced OA animals. The pain threshold, cartilage damage, and inflammation of the joint synovial membrane were improved by live LA-1. Furthermore, the analysis of intestinal tissues and feces in the disease model has been shown to affect the systems of the intestinal system and improve the microbiome environment. Interestingly, inflammation of the intestinal tissue was reduced, and the intestinal microbiome was altered by live LA-1. Live LA-1 administration led to an increase in the level of which is a short-chain fatty acid (SCFA) butyrate-producing bacteria. The daily supply of butyrate, a bacterial SCFA, showed a tendency to decrease necroptosis, a type of abnormal cell death, by inducing autophagy and reversing impaired autophagy by the inflammatory environment. These results suggest that OA is modulated by changes in the gut microbiome, suggesting that activation of autophagy can reduce aberrant cell death. In summary, live LA-1 or butyrate ameliorates OA progression by modulating the gut environment and autophagic flux. Our findings suggest the regulation of the gut microenvironment as a therapeutic target for OA.

The levels of some migraine biomarkers differ between episodic migraine (EM) and chronic migraine (CM), but information on C-reactive protein (CRP) levels in EM and CM is conflicting. Thus, this study aimed to evaluate CRP levels in participants with EM and CM in comparison to those in healthy controls.

Distal symmetric diabetic peripheral polyneuropathy (DPN) is the most common form of neuropathy in the world, affecting 30 to 50% of diabetic individuals and resulting in significant morbidity and socioeconomic costs. This review summarizes updates in the diagnosis and management of DPN. Recently updated clinical criteria facilitate bedside diagnosis, and a number of new technologies are being explored for diagnostic confirmation in specific settings and for use as surrogate measures in clinical trials. Evolving literature indicates that distinct but overlapping mechanisms underlie neuropathy in type 1 versus type 2 diabetes, and there is a growing focus on the role of metabolic factors in the development and progression of DPN. Exercise-based lifestyle interventions have shown therapeutic promise. A variety of potential disease-modifying and symptomatic therapies are in development. Innovations in clinical trial design include the incorporation of detailed pain phenotyping and biomarkers for central sensitization.

Chronic bleeding disorders, allergy to implants, and chronic infections are all complicating factors when considering neuromodulation therapies. The American Society of Pain and Neuroscience (ASPN) determined a need for clinical guidance in these special patient populations that have increased risk of complications, in order to ensure patient safety and optimal outcomes with device implantation. The purpose of this publication was to review the published literature and explore the unique clinical challenges encountered among several special patient populations with relation to spinal cord stimulation. The executive board of the ASPN appointed a diverse group of well-established physicians to develop best practice guidelines regarding spinal cord stimulation implantation in these special populations. The physicians used the United States Preventive Services Task Force (USPSTF) structured guidelines for grading and level of certainty to make evidence-based recommendations about clinical practice. Where sufficient evidence was lacking to justify a USPSTF ranking, the physicians queried experts in neuromodulation and achieved consensus. These best practices and interventional guideline found the evidence for the use of neuromodulation in specialized patient populations to be relatively modest.