Risk Factors for Bloodstream Infections Among an Urban Population with Skin and Soft Tissue Infections: A Retrospective Unmatched Case-Control Study

Introduction: The prevalence of acute bacterial skin and skin structure infections (ABSSSIs) continues to increase. Bloodstream infection (BSI) is a severe secondary complication of ABSSSI. The objective of this study was to determine clinical and sociodemographic risk factors for BSI in patients with acute bacterial skin and skin structure infections (ABSSSIs) and to determine if sociodemographic factors impact severity at presentation. Methods This was a retrospective unmatched (1:1) case-control study. Predictors of BSI and severe infection were sought through multivariable logistic regression analyses. Cases and controls were collected from two major medical centers located in downtown Detroit, Michigan: the Detroit Medical Center and the Henry Ford Health System. The population of interest included adult patients with community-onset (CO) ABSSSI treated at a participating hospital between January 2010 and December 2015. Cases were defined as those developing BSI within 48 h of admission with CO-ABSSSI as the primary source, while controls were those with CO-ABSSSI without BSI. Results A total of 392 patients (196 cases, 196 controls) were included. Independent predictors of BSI were male gender (aOR 1.85: 95% CI 1.11, 3.66), acute renal failure (aOR 2.08: 95% CI 1.18, 3.66), intravenous drug use (aOR 4.38, 95% CI 2.22, 8.62), and prior hospitalization (aOR 2.41, 95% CI 1.24, 4.93). African American race (aOR 2.18, 95% CI 1.38, 3.4), leukocytosis (aOR 2.24, 95% CI 1.41, 3.55), and prior hospitalization (aOR 2.07, 95% CI 1.19, 3.00) were significantly associated with infection severity. Conclusion Both clinical and sociodemographic factors were associated with BSI and severe infection underscoring the importance of social determinants of health in outcomes among underserved populations

Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis

Background and purpose: Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment. // Methods: A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT 00731692) was undertaken. Data were available from 324 patients with magnetic resonance imaging scans up to 3 years after screening. New lesions at year 1 were identified with convolutional neural networks, and SELs obtained through a deformation-based method. Clinical disability was assessed annually by Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test, Timed 25-Foot Walk, and Paced Auditory Serial Addition Test. Linear, logistic, and mixed-effect models were used to assess the relationship between the Jacobian expansion in new lesions and SELs, disability scores, and treatment status. // Results: One hundred seventy patients had ≥1 new lesions at year 1 and had a higher lesion count at screening compared to patients with no new lesions (median = 27 vs. 22, p = 0.007). Among the new lesions (median = 2 per patient), 37% evolved into definite or possible SELs. Higher SEL volume and count were associated with EDSS worsening and confirmed disability progression. Treated patients had lower volume and count of definite SELs (β = −0.04, 95% confidence interval [CI] = −0.07 to −0.01, p = 0.015; β = −0.36, 95% CI = −0.67 to −0.06, p = 0.019, respectively). // Conclusions: Incident chronic active lesions are common in PPMS, and fingolimod treatment can reduce their number

Menstruation angina: a case report

<p>Abstract</p> <p>Introduction</p> <p>Menstruation is commonly associated with migraine and irritable bowel but is rarely correlated with angina or myocardial ischaemia. Only a small number of cases have been reported suggesting a link between menstruation and myocardial ischaemic events.</p> <p>Case presentation</p> <p>A case of menstruation angina is reported in order to raise awareness of this association. A 47-year-old South Asian woman presented with recurrent chest pains in a monthly fashion coinciding with her menstruations. Each presentation was associated with troponin elevation. Angioplasty failed to resolve her symptoms but she eventually responded to hormonal therapy.</p> <p>Conclusions</p> <p>The possibility of menstruation angina should always be taken into account in any female patients from puberty to menopause presenting with recurrent chest pains. This can allow an earlier introduction of hormonal therapy to arrest further myocardial damage.</p

Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR

We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR −/−) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37°C for up to 9 days and displayed a terminal half-life (T1/2β) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that 125I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of' 111In-labelled ch806 was demonstrated with uptake of 31%ID g−1 and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent

Noninvasive Assessment of Antenatal Hydronephrosis in Mice Reveals a Critical Role for Robo2 in Maintaining Anti-Reflux Mechanism

Antenatal hydronephrosis and vesicoureteral reflux (VUR) are common renal tract birth defects. We recently showed that disruption of the Robo2 gene is associated with VUR in humans and antenatal hydronephrosis in knockout mice. However, the natural history, causal relationship and developmental origins of these clinical conditions remain largely unclear. Although the hydronephrosis phenotype in Robo2 knockout mice has been attributed to the coexistence of ureteral reflux and obstruction in the same mice, this hypothesis has not been tested experimentally. Here we used noninvasive high-resolution micro-ultrasonography and pathological analysis to follow the progression of antenatal hydronephrosis in individual Robo2-deficient mice from embryo to adulthood. We found that hydronephrosis progressed continuously after birth with no spontaneous resolution. With the use of a microbubble ultrasound contrast agent and ultrasound-guided percutaneous aspiration, we demonstrated that antenatal hydronephrosis in Robo2-deficient mice is caused by high-grade VUR resulting from a dilated and incompetent ureterovesical junction rather than ureteral obstruction. We further documented Robo2 expression around the developing ureterovesical junction and identified early dilatation of ureteral orifice structures as a potential fetal origin of antenatal hydronephrosis and VUR. Our results thus demonstrate that Robo2 is crucial for the formation of a normal ureteral orifice and for the maintenance of an effective anti-reflux mechanism. This study also establishes a reproducible genetic mouse model of progressive antenatal hydronephrosis and primary high-grade VUR

Molecular targeted therapies in head and neck cancer - An update of recent developements -

Targeted therapies have made their way into clinical practice during the past decade. They have caused a major impact on the survival of cancer patients in many areas of clinical oncology and hematology. Indeed, in some hematologic malignancies, such as chronic myelogenous leukemia or non-Hodgkin's lymphomas, biologicals and antibodies specifically designed to target tumour-specific proteins have revolutionized treatment standards. In solid tumours, new drugs targeting EGF- or VEGF- receptors are now approved and are entering clinical practise for treatment of colon, lung, kidney and other cancers, either alone or in combination with conventional treatment approaches

Bisphenol A and 17β-Estradiol Promote Arrhythmia in the Female Heart via Alteration of Calcium Handling

There is wide-spread human exposure to bisphenol A (BPA), a ubiquitous estrogenic endocrine disruptor that has been implicated as having potentially harmful effects on human heart health. Higher urine BPA concentrations have been shown to be associated with cardiovascular diseases in humans. However, neither the nature nor the mechanism(s) of BPA action on the heart are understood. leak suppressed estrogen-induced triggered activities. The rapid response of female myocytes to estrogens was abolished in an estrogen receptor (ER) β knockout mouse model. leak. Our study provides the first experimental evidence suggesting that exposure to estrogenic endocrine disrupting chemicals and the unique sensitivity of female hearts to estrogens may play a role in arrhythmogenesis in the female heart