Neuropathic pain and diabetes

Neuropathic pain is a common phenomenon resulting from injury to the central or peripheral nervous system. The means by which diabetes results in nerve injury is unclear but the effect is to cause injury at all levels of the nervous system from the level of the peripheral nerves to the brain. Nerve injury causes pain through a cascade of mechanisms resulting in altered processing of sensory input into the nervous system. This alteration occurs through chemical and anatomical changes in the nervous system that are similar to some of the processes seen in central sensitisation following acute pain. Following nerve injury, neuropathic pain occurs not only when these mechanisms are activated but also when sensitisation is maintained. Other processes occurring in neuropathic pain appear to be a loss of normal inhibitory controls as seen by a reduction in local GABA-ergic and descending monoaminergic influences. There are also important changes mediated via glial cells that can maintain neuropathic pain. Diabetes affects all areas of the nervous system and the contribution of higher levels of the nervous system is often overlooked. Neurophysiological and MRI evidence strongly suggest that these may contribute to the pain of diabetic neuropathy. Psychological dysfunction in diabetic patients is an important factor in increasing the suffering associated with all aspects of the disease, but treatment and control of pain can greatly improve the quality of life.     

Reference values of ECG parameters derived from 906 echocardiographically confirmed healthy Indian children: A population-based study from Gujarat

Introduction

There are few published studies on reference ranges of ECG parameters in children; some ethnic differences have been described.

Tuberculosis of the hip in children: A retrospective analysis of 27 patients

Background:

We retrospectively evaluated the pretreatment radiological presentation and the clinicoradiological outcome at the completion of 1 year chemotherapy in osteoarticular tuberculosis of hip in children to prognosticate correlation between them.

Materials and Methods:

We retrospectively analyzed the clinical and plain radiographic findings in 27 patients with an age of 12 years or younger in whom hip tuberculosis was diagnosed and treated between 2006 and 2010. The diagnosis was based on histopathology in 14 and clinicoradiological basis in 13 patients. The pre and post treatment plain radiographs were evaluated according to Shanmugasundaram radiological classification and our observations regarding unclassified cases which were not fit in this classification were suggested. The functional outcome at the completion of chemotherapy was assessed using modified Moon''s criteria.

Results:

The male female ratio was 11:16. The left hip was involved more frequently than the right (17:10). The average age was 7.37 years (range, 2-12 years). In the pretreatment radiographs, 9 hips were normal, 6 traveling, 4 dislocating, 1 protrusio acetabuli, 3 atrophic and 4 unclassified types (3 triradiate; 1 pseudarthrosis coxae). There were no Perthes and mortar pestle at the initial presentation. Posttreatment, the types changed to 9 normal, 3 Perthes, 1 protrusio acetabuli, 1 atrophic, 4 mortar pestle and 9 unclassified types (3 triradiate, 3 pseudarthrosis coxae and 3 ankylosed). There were 37% excellent, 18.5% good, 26% fair and 18.5% poor results. The prognosis was best with initial “triradiate” and normal types and worst with posttreatment atrophic and “ankylosed” types.

Conclusions:

The Shanmugasundaram radiological types accurately predict prognosis only in normal types and “triradiate” pattern. The functional outcome is independent of radiological morphology of the hip in smaller children.     

Atypical Mycobacterial Infection in Hairy Cell Leukemia Treated with Cladribine

We report a case of hairy cell leukemia who improved after cladribine but succumbed to disseminated atypical mycobacterial infection 2 months after completing cladribine.     

Beyond survival: how well do transplanted livers work? A preliminary comparison of standard‐risk,high‐risk,and living donor recipients

To help decrease mortality on the liver transplant waitlist, transplant centers are using living donors (LD) and high‐risk donors (HRD) in addition to standard‐risk donors (SRD). HRD is defined as having a donor risk index score higher than 1.6, which suggests a great risk of graft failure. Recent studies have examined survival rates between HRD and SRD recipients; however, little is known about outcomes other than survival, specifically psychosocial outcomes. The purpose of this preliminary, prospective study was to compare post‐transplant psychosocial and recovery outcomes between SRD and LD and HRD liver recipients. These outcomes include cognitive functioning, psychological distress, quality of life, and self‐reported and objective measures of recovery. Eighty‐four patients provided baseline and six‐month post‐transplant data. There were generally no statistically significant differences at baseline or the six‐month follow‐up, suggesting that patients receiving HRD livers have similar outcomes to those who receive SRD livers. However, some effect sizes suggest potential advantages for LD recipients compared to SRD recipients. Transplant centers may be more willing to encourage patients to accept HRD or LD livers knowing that they may have comparable outcomes to SRD recipients, which also has implications for the transplant waitlist.     

Validation of the Chronic Pain Acceptance Questionnaire-8 in an Australian Pain Clinic Sample

Background

Recently, an 8-item short-form version of the Chronic Pain Acceptance Questionnaire (CPAQ-8) was developed predominantly in an internet sample. Further investigation of the factor structure in a multidisciplinary pain clinic sample is required. Investigation of the concurrent validity of the CPAQ-8 after accounting for the effects of variables commonly measured in the pain clinic setting is also necessary.

Purpose

This study examines the factor structure and concurrent validity of the CPAQ-8 in a sample of treatment-seeking patients who attended a multidisciplinary pain clinic.

Methods

Participants were 334 patients who attended an Australian multidisciplinary pain service. Participants completed the CPAQ, a demographic questionnaire, and measures of patient adjustment and functioning.

Results

Confirmatory factor analysis identified a two-factor 8-item model consisting of Activity Engagement and Pain Willingness factors (SRMR?=?0.039, RMSEA?=?0.063, CFI?=?0.973, TLI?=?0.960) was superior to both the CPAQ and CPAQ with an item removed. The CPAQ and CPAQ-8 total scores were highly correlated (r?=?0.93). After accounting for pain intensity, the CPAQ-8 was a significant predictor of depression, anxiety, stress, and disability. The subscales of the CPAQ-8 were both unique contributors to depression and disability in regression analyses, after accounting for pain intensity and kinesiophobia, and after accounting for pain intensity and catastrophizing.

Conclusions

The CPAQ-8 has a sound factor structure and similar psychometric properties to the CPAQ; it may have clinical utility as a measure of pain acceptance in treatment-seeking, chronic pain patients.     

Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma

Tumor Treating Fields (TTFields), an approved therapy for glioblastoma (GBM) and malignant mesothelioma, employ noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to disrupt the mitotic spindle, leading to chromosome missegregation and apoptosis. Emerging evidence suggests that TTFields may also induce inflammation. However, the mechanism underlying this property and whether it can be harnessed therapeutically are unclear. Here, we report that TTFields induced focal disruption of the nuclear envelope, leading to cytosolic release of large micronuclei clusters that intensely recruited and activated 2 major DNA sensors — cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) — and their cognate cGAS/stimulator of interferon genes (STING) and AIM2/caspase 1 inflammasomes to produce proinflammatory cytokines, type 1 interferons (T1IFNs), and T1IFN-responsive genes. In syngeneic murine GBM models, TTFields-treated GBM cells induced antitumor memory immunity and a cure rate of 42% to 66% in a STING- and AIM2-dependent manner. Using single-cell and bulk RNA sequencing of peripheral blood mononuclear cells, we detected robust post-TTFields activation of adaptive immunity in patients with GBM via a T1IFN-based trajectory and identified a gene panel signature of TTFields effects on T cell activation and clonal expansion. Collectively, these studies defined a therapeutic strategy using TTFields as cancer immunotherapy in GBM and potentially other solid tumors.