In schizophrenia,non-remitters and partial remitters to treatment with antipsychotics are qualitatively distinct classes with respect to neurocognitive deficits and neuro-immune biomarkers: results of soft independent modeling of class analogy

Around one third of schizophrenia patients are non-responders to antipsychotic therapy. The present study aimed to delineate the pathway-phenotypes of non-remitters (NRTT) and partial remitters (PRTT) to treatment with antipsychotics as defined using the Global Clinical Impression scales. We recruited 60 NRTT, 50 PRTT and 43 healthy controls and measured schizophrenia symptoms, neurocognitive tests, plasma CCL11, interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box-1 protein (HMGB1), κ- and μ-opioid receptors (KOR and MOR, respectively), endomorphin-2 (EM-2), and β-endorphin. Soft independent modeling of class analogy (SIMCA) showed that NRTT and PRTT are significantly discriminated with a cross-validated accuracy of 94.7% and are qualitatively distinct classes using symptomatome, and neuro-immune-opioid-cognitome (NIOC) features as modeling variables. Moreover, a NIOC pathway phenotype discriminated PRTT from healthy controls with an accuracy of 100% indicating that PRTT and controls are two qualitative distinct classes. Using NIOC features as discriminatory variables in SIMCA showed that all PRTT were rejected as belonging to the normal control class and authenticated as belonging to their target class. In conclusion, a non-response to treatment can best be profiled using a SIMCA model constructed using symptomatome and NIOC features. A partial response should be delineated using SIMCA by authenticating patients as controls or PRTT instead of using scale-derived cut-off values or a number of scale items being rated mild or better. The results show that PRTT is characterized by an active NIOC pathway phenotype and that both NRTT and PRTT should be treated by targeting neuro-immune and opioid pathways.

     

Hospitalisation costs associated with heart failure with preserved ejection fraction (HFpEF): a systematic review

Heart Failure Reviews - Heart failure with preserved ejection fraction (HFpEF) is problematic to treat, with guidelines for HFpEF management concentrated on treating prevalent comorbidities. The...     

Spectrum of microscopic colitis in a tertiary care centre in India

INTRODUCTION: The incidence of microscopic colitis has recently increased. Although collagenous colitis and lymphocytic colitis are the two main subtypes of microscopic colitis, many patients may not fit into either category and are thus included under the header nonspecific colitis. Of late, the spectrum of microscopic colitis has widened to include minimal change colitis, microscopic colitis not otherwise specified and microscopic colitis with giant cells. There is a lack of information concerning the spectrum of microscopic colitis in Asia. METHOD: In a retrospective analysis, case records of 29 patients diagnosed with microscopic colitis between 1999-2005 were analysed. Drug use parasitic infection and common bacterial infections were excluded. Colonoscopic/ sigmoidoscopic examination was done and multiple colonic mucosal biopsies were stained serially with haematoxylin and eosin for detailed histological examination and Masson trichrome for sub-epithelial collagen band. Based on histological criteria, patients were categorised into five subtypes: collagenous colitis (presence of collagenous thickening of surface epithelium basement membrane > 10 microm), lymphocytic colitis (intra-epithelial lymphocytes more than 20 per 100 colonocytes), minimal change colitis (crypt architectural abnormality in the form of cryptitis and crypt dilatation in the absence of increase in intraepithelial lymphocytes and subepithelial collagenous band), microscopic colitis not otherwise specified (increased inflammatory cell infiltrates in the lamina propria in the absence of other abnormalities) and microscopic colitis with giant cells. RESULTS: Mean age of patients was 38.59 years (range 12-62). Of 29 patients with microscopic colitis, 7 (24.1%), 4 (13.8%), 7 (24.1%) and 11 (37.9%) were classified as collagenous colitis, lymphocytic colitis, minimal change colitis and microscopic colitis not otherwise specified, respectively. None of these patients had giant cells. There was no significant correlation between disease type and clinical manifestations. CONCLUSION: Microscopic colitis has a wide histological spectrum. Cases reported as non-specific colitis, may be categorised into definite subtypes of microscopic colitis.     

Assessment of inflamed synovial membrane in the knee joint by dynamic magnetic resonance imaging

Dynamic magnetic resonance imaging (dynamic MRI) was used to examine the synovial membrane in the knee joints of 15 patients with rheumatoid arthritis (RA) in order to investigate the relationship between pathological and MRI findings. Signal intensities in the regions of interest (ROI), identified as the synovial membrane of the suprapatellar pouch, were measured on MR images. Signal intensities at various times after the injection of contrast medium Gd–diethylenetriaminopentoacetic acid (Gd–DTPA) were normalized relative to the signal intensity at 80s, and designated as the normalized signal intensity (NSI). Pathological findings were quantified, and the types of inflamed synovial membrane were classified as either acute or chronic. A significant difference in NSI was observed between acute and chronic types (P 0.05). Dynamic MRI was capable of classifying acute and chronic RA by measuring NSI 20s after contrast medium injection. Dynamic MRI was therefore shown to be useful for assessing regional synovial inflammation.     

Solitary rectal ulcer syndrome in children and adolescents: a descriptive clinicopathologic study

Solitary rectal ulcer syndrome (SRUS) is an uncommon disorder of the rectum. While benign, it can cause concern for patients and affect quality of life. Reported studies on SRUS worldwide are scarce. The aim of this study is to describe the clinicopathologic characteristics of SRUS in a cohort of children based in Saudi Arabia. In this study, children with a confirmed diagnosis of SRUS at King Abdulaziz University Hospital (KAUH) were included, during the period November 2003 to November 2017. Data were collected from hospital medical records. The study comprised twenty-one patients: 17 males (81%) and 4 females (19%); the median age was 11.4 years (range, 5.43-17.9 years). The most common presenting symptoms were rectal bleeding in 21 patients (100%), passage of mucus in 16 (76.1%), abdominal pain in 14 (66.6%), constipation in 13 (61.9%), straining in 9 (42.9%), and rectal prolapse in 5 (23.8%). The most common finding at initial colonoscopy was a single ulcer in 7 patients (33.3%), multiple ulcers in 6 (28.5%), polypoid lesions in 5 (23.8%), and hyperemic mucosa in 3 (14.2%). All patients received medical treatment and 14 (81%) continued to manifest one or more of the symptoms following treatment, which required subsequent modification of the treatment course. None of the patients required surgery. In conclusion, the study found rectal bleeding to be the most common presentation, with a single ulcer being the most prevalent lesion in endoscopy. Treatment response was variable, but almost half of patients reported relief of symptoms following treatment.     

Effects of Denosumab,Alendronate, or Denosumab Following Alendronate on Bone Turnover,Calcium Homeostasis,Bone Mass and Bone Strength in Ovariectomized Cynomolgus Monkeys

Postmenopausal osteoporosis is a chronic disease wherein increased bone remodeling reduces bone mass and bone strength. Antiresorptive agents including bisphosphonates are commonly used to mitigate bone loss and fracture risk. Osteoclast inhibition via denosumab (DMAb), a RANKL inhibitor, is a newer approach for reducing fracture risk in patients at increased risk for fracture. The safety of transitioning from bisphosphonate therapy (alendronate; ALN) to DMAb was examined in mature ovariectomized (OVX) cynomolgus monkeys (cynos). One day after OVX, cynos (7–10/group) were treated with vehicle (VEH, s.c.), ALN (50 μg/kg, i.v., twice monthly) or DMAb (25 mg/kg/month, s.c.) for 12 months. Other animals received VEH or ALN for 6 months and then transitioned to 6 months of DMAb. DMAb caused significantly greater reductions in serum CTx than ALN, and transition from ALN to DMAb caused further reductions relative to continued ALN. DMAb and ALN decreased serum calcium (Ca), and transition from ALN to DMAb resulted in a lesser decline in Ca relative to DMAb or to VEH‐DMAb transition. Bone histomorphometry indicated significantly reduced trabecular and cortical remodeling with DMAb or ALN. Compared with ALN, DMAb caused greater reductions in osteoclast surface, eroded surface, cortical porosity and fluorochrome labeling, and transition from ALN to DMAb reduced these parameters relative to continued ALN. Bone mineral density increased in all active treatment groups relative to VEH controls. Destructive biomechanical testing revealed significantly greater vertebral strength in all three groups receiving DMAb, including those receiving DMAb after ALN, relative to VEH controls. Bone mass and strength remained highly correlated in all groups at all tested skeletal sites, consistent with normal bone quality. These data indicate that cynos transitioned from ALN to DMAb exhibited reduced bone resorption and cortical porosity, and increased BMD and bone strength, without deleterious effects on Ca homeostasis or bone quality. © 2014 American Society for Bone and Mineral Research.