Matrix metalloproteinase production by COOH-terminal heparin-binding fibronectin fragment in rheumatoid synovial cells

Fibronectin with IIICS region is present in rheumatoid synovium, and fibronectin fragments are increased in rheumatoid joints. We investigated the ability of COOH-terminal heparin-binding fibronectin fragment (COOH-HBFN-f) containing IIICS to induce matrix metalloproteinase (MMP) production and the role of mitogen-activated protein kinase (MAPK) pathway and CS-1 sequence that can bind alpha4beta1 integrin in MMP induction by COOH-HBFN-f in rheumatoid synovial fibroblasts (RSF). When RSF in monolayer culture were incubated with COOH-HBFN-f, COOH-HBFN-f stimulated the production of MMP-1, MMP-3, and MMP-13 by RSF in association with activation of extracellular signal-regulated kinase, p38 MAPK, and c-Jun NH(2)-terminal kinase. Immunoprecipitation of cell lysates demonstrated the presence of alpha4 integrin in cultured RSF. Similar to COOH-HBFN-f, treatment with CS-1 synthetic peptide derived from IIICS resulted in increased MMP production and activation of the kinases, although the MMP levels were low. Preincubation of RSF with anti-alpha4 integrin antibody resulted in partial suppression of the COOH-HBFN-f-stimulated MMP production. Inhibition studies using protein kinase inhibitors (PD98059 and SB203580) showed that those MAPK pathways contributed to MMP up-regulation by COOH-HBFN-f and CS-1. Thus, the present results have clearly shown that COOH-HBFN-f and CS-1 stimulate MMP production in association with activation of MAPK pathways in RSF. Integrin alpha4beta1 may be partially involved in the MMP induction by COOH-HBFN-f.     

Examining Trichophyton tonsurans genotype and biochemical phenotype as determinants of disease severity in tinea capitis.

Trichophyton tonsurans infections occur in various host populations, on various body sites and with varying degrees of inflammation. This investigation was undertaken to determine whether fungal factors could explain the degree of severity in clinical symptomatology among infected children. Otherwise healthy children (n=54) presenting with tinea capitis were enrolled in this study. A thorough history was performed, the extent and severity of infection graded and a fungal specimen collected from each child. Strain type was determined by genotyping for 11 sequence variations in the rDNA and ALP1 loci. Secreted protease activity was quantitated after 5 days of growth in aqueous medium. Forty participants were evaluable. Infection duration ranged from 1 day to 3 years and clinical severity score (CSS) from 4-19. Seventeen unique fungal genotypes were present. Keratinase, collagenase and elastase activity varied 32.7-fold, 64.9-fold and 303.3-fold, respectively. A significant association was observed between genotype and disease severity with the rDNA sequence variations accounting for over 50% of the variation observed in CSS (r2=0.539; P<0.001). Phylogenetic analyses appear to suggest that the ancestral strain types of T. tonsurans cause more severe disease. These observations are consistent with reports that recently diverge anthropophilies are associated with diminished inflammatory involvement.     

HbA1c over 8.5% is not predictive of increased infection rate following penile prosthesis implant surgery in diabetic patients with erectile dysfunction

Diabetes mellitus is associated with increased risk of erectile dysfunction. Penile prosthesis implantation is an efficient therapeutic option for erectile dysfunction, but not without risk, as infection remains a prominent concern. This study investigates diabetes mellitus as a risk factor for penile prosthesis implantation infection and the relationship between haemoglobinA1c levels and infection rates. All diabetic patients with erectile dysfunction who underwent penile prosthesis implantation surgery between January 2012 and November 2019 at Hamad Medical Corporation, Qatar, were included in this retrospective observational study. A total of 599 diabetic patients with erectile dysfunction had penile prosthesis implantation. Mean age was 59.69 ± 31.19. Penile prosthesis implantation infection rate was 0.83% (5/599), while the mean haemoglobinA1c level was 7.58 ± 1.45 mmol/l (range: 4.1–12.6). A comparison between diabetic patients with penile prosthesis implantation infection and those without infection revealed no significant difference in the level of haemoglobinA1c between the two groups with mean haemoglobinA1c in patients with infected implants 7.14 and 7.59 for noninfected (p = 0.491). Limitations include retrospective single-centre design and low-infection rates reducing sample number. Penile prosthesis implantation infection rate in a large series of diabetic patients was low with no significant association between haemoglobinA1c level and penile prosthesis implantation infection observed.     

Basement membrane thickening in the placentae from diabetic women

A light microscopy study was carried out on 48 placentae. Seventeen placentae were obtained from non-diabetic mothers while the other 31 placentae were from both women with controlled diabetes and women who had an abnormality of the glucose tolerance test. All the women delivered at 38-40 weeks of gestation. Placentae from diabetic patients showed immaturity of the villi, hypertrophy of the capillaries and thickening of the basement membrane of the trophoblastic villi (3.2 +/- 0.35 microns) and the amniotic membrane (1.8 +/- 0.3 microns). Focal fibrinoid necrosis, an increase in the number of Hofbauer cells and dilatation of villi capillaries were also commonly observed in placentae from diabetic mothers, and the normal cuboidal cells lining the amniotic membrane tended to become tall columnar (17.6 +/- 6.3 microns) with distally located nuclei. Similar findings were observed in patients who had a potentially abnormal glucose tolerance test, which suggests the possibility of primary lesion in origin. Therefore, control of hyperglycemia may only partially prevent the development of placental abnormalities.     

Imaging spectrum in disseminated histoplasmosis: Case report and brief review

The clinical manifestations of chronic disseminated histoplasmosis are non-specific and resemble those of other chronic infections and malignancies. We report the radiographic, sonographic and contrast-enhanced CT appearances of histoplasmosis in an adult male with non-insulin dependent diabetes mellitus, who was HIV negative and presented with weight loss and pyrexia. Imaging studies simulated tuberculosis with mediastinal lymphadenopathy, bilateral fibrotic lung lesions, hepatomegaly and bilateral hypoattenuating adrenal enlargement, without clinical or laboratory evidence of hypoadrenalism. Computed tomography-guided fine-needle aspiration biopsy of adrenal glands revealed Histoplasma capsulatum. We report our experience to increase awareness of the imaging spectrum of disseminated histoplasmosis and its similarity to tuberculosis as, with increasing incidence of AIDS, the chances of these infections are likely to increase. Moreover, awareness of this entity is important because it is known that untreated disseminated histoplasmosis is fatal.     

Incorporating PROMIS Symptom Measures into Primary Care Practice—a Randomized Clinical Trial

Background

Symptoms account for more than 400 million clinic visits annually in the USA. The SPADE symptoms (sleep, pain, anxiety, depression, and low energy/fatigue) are particularly prevalent and undertreated.

Objective

To assess the effectiveness of providing PROMIS (Patient-Reported Outcome Measure Information System) symptom scores to clinicians on symptom outcomes.

Design

Randomized clinical trial conducted from March 2015 through May 2016 in general internal medicine and family practice clinics in an academic healthcare system.

Participants

Primary care patients who screened positive for at least one SPADE symptom.

Interventions

After completing the PROMIS symptom measures electronically immediately prior to their visit, the 300 study participants were randomized to a feedback group in which their clinician received a visual display of symptom scores or a control group in which scores were not provided to clinicians.

Main Measures

The primary outcome was the 3-month change in composite SPADE score. Secondary outcomes were individual symptom scores, symptom documentation in the clinic note, symptom-specific clinician actions, and patient satisfaction.

Key Results

Most patients (84%) had multiple clinically significant (T-score?≥?55) SPADE symptoms. Both groups demonstrated moderate symptom improvement with a non-significant trend favoring the feedback compared to control group (between-group difference in composite T-score improvement, 1.1; P?=?0.17). Symptoms present at baseline resolved at 3-month follow-up only one third of the time, and patients frequently still desired treatment. Except for pain, clinically significant symptoms were documented less than half the time. Neither symptom documentation, symptom-specific clinician actions, nor patient satisfaction differed between treatment arms. Predictors of greater symptom improvement included female sex, black race, fewer medical conditions, and receiving care in a family medicine clinic.

Conclusions

Simple feedback of symptom scores to primary care clinicians in the absence of additional systems support or incentives is not superior to usual care in improving symptom outcomes.

Trial Registration

clinicaltrials.gov identifier: NCT02383862.

     

Chronic endogenous fungal endophthalmitis: diagnostic and treatment challenges: A case report

Rationale:Endogenous fungal endophthalmitis (EFE) is a sight-threatening complication of systemic fungemia. As the prevalence rises, treatment remains a challenge especially when there is a failure in first-line treatment or drug-resistant fungus. This case report studies a case of chronic EFE, focusing on the diagnostic procedures, treatment options, monitoring parameters and the treatment outcomePatient concerns:A 64-year-old man with underlying well controlled diabetes mellitus was treated with 2 weeks’ course of intravenous antifungal fluconazole for pyelonephritis as his blood culture grew Candida albicans. Concurrently, he complained of 3 months of bilateral painless progressive blurring of vision. At presentation, his visual acuity (VA) was light perception both eyes. Ocular examination revealed non granulomatous inflammation with dense vitritis of both eyes.Diagnosis:He was diagnosed with EFE but the condition responded poorly with the medications.Interventions:He was treated with intravitreal (IVT) amphotericin B and fluconazole was continued. Vitrectomy was performed and intraoperative findings included bilateral fungal balls in the vitreous and retina with foveal traction in the left eye. Postoperatively, vision acuity was 6/24, N8 right eye and 2/60, N unable for left eye with extensive left macular scar and hole. Vitreous cultures were negative. He received multiple IVT amphotericin B and was started on topical steroid eye drops for persistent panuveitis with systemic fluconazole. Ocular improvement was seen after switching to IVT and topical voriconazole. Despite this, his ocular condition deteriorated and he developed neovascular glaucoma requiring 3 topical antiglaucoma agents. Panretinal photocoagulation was subsequently performed.Outcomes:At 3 months’ follow-up, his vision acuity remained at 6/24 for right eye and 2/60 for the left eye. There was no recurrence of inflammation or infection in both eyes.Lessons:Voriconazole could serve as a promising broad spectrum tri-azole agent in cases of failure in first-line treatment or drug-resistant fungus.