A Retrospective,Longitudinal External Study of the robustness and reproducibility of National Antibacterial Prescribing Survey Data

International Journal of Clinical Pharmacy - Point prevalence surveys are used internationally to audit antibacterial use as well as the impact of interventions on improving prescribing and...     

PVP‐co‐DMAEMA as Novel Polymeric Coating Material for Probiotic Supplements Delivery

The paper investigates the use of poly(1‐vinylpyrrolidone‐co‐2‐dimethylaminoethylmetacrilate) (PVP‐co‐DMAEMA) as a novel coating agent in the preparation of alginate‐based microcapsule for the supplement delivery of probiotics. Probiotic Lactobacillus plantarum is used to study the viability of the encapsulated bacterium when exposed to conditions simulating the gastrointestinal tract and industrial process. Results demonstrate that the PVP‐co‐DMAEMA polymer constitutes a pH‐responsive coating suitable for probiotic supplement delivery.     

Markers of acute neuropsychiatric systemic lupus erythematosus: a multidisciplinary evaluation

This study was aimed to assess: (1) the additive diagnostic utility of diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) over conventional MRI in detecting brain lesions in patients with acute primary neuropsychiatric systemic lupus erythematosus (NPSLE), and (2) the relevance of their findings to the associated NP manifestations. Included were 34 patients with acute NPSLE with mean age of 33.26 ± 10.14 years and duration of illness of 3.33 ± 1.71 years. Clinical interviewing and psychiatric and cognitive evaluations were performed by applying the criteria of the diagnostic and statistical manual of mental health disorders criteria (DSM–IV), Stanford Binet Subset Testing, Mini-Mental State Examination and Wechsler Memory Scale-Revised. Serologic tests included looking for antinuclear antibodies, anti-double strand DNA, anti-phospholipid antibodies. Radiologic evaluation included conventional MRI, DWI and MRA. One or more NP manifestations were diagnosed in 28 patients, in which cognitive deficits were reported with headache, psychosis and CVS. Anti-phospholipid antibodies were reported in patients with CVS. Twenty patients (71.43 %) with primary NPSLE (n = 28) had MRI abnormalities in which hyperintense signals at subcortical and periventricular white matter and at the junction between the gray and white matter represented 75 % (n = 15) and with headache (n = 6), psychosis (n = 6) and acute confusional state (n = 3) with and without cognitive deficits, respectively. Moderate-sized infarctions with restricted diffusion in the distribution of middle cerebral arteries were represented in 35 % (n = 7) and with CVS, of them, 71.43 % (n = 5) had beading and focal narrowing of carotid arteries were consistent with vasculitis. Brain atrophy represented 20 % (n = 4) and with psychosis. Compared to those with normal MRI, patients with MRI abnormalities were older (P < 0.050) and had longer duration of illness (P < 0.050). To conclude, although DWI and MRA are helping in more precise etiopathologic diagnosis compared to conventional MRI, but their relevance to the present NP manifestations is still limited.     

Immunohistochemical Expression of PD-L1 and IDH1 with Detection of MGMT Promoter Methylation in Astrocytoma

Objective: Programmed death ligand 1 (PD-L1) expression was suggested as a poor prognostic predictor for glioblastoma. While isocitrate dehydrogenase (IDH) has been linked to enhanced overall survival in glioma cells. In glioblastoma patients receiving treatment with alkylating drugs, the methylguanine-DNA methyltransferase (MGMT) promoter’s methylation status has been discovered as a potent and distinct predictor of good survival. In this study, we aimed to investigate the expression rate of PD-L1, IDH1, and MGMT methylation in patients with different grades of  astrocytoma. Methods: The present retrospective study retrieved the data and archived paraffin blocks of 60 cases of astrocytoma. Immunohistochemical evaluation was done to assess the expressions of PD-L1 and IDH1, Methylation-specific-PCR was used to investigate the MGMT promoter. Results: This study included astrocytoma grade II 18% (11/60), grade III 22% (13/60), grade IV 60% (36 cases). PD-L1 expression was detected in 82% of all studied cases (49/60) while IDH1 mutant astrocytoma were 73% (44/60) & methylation was reported in 58.3% (35 cases). High grade astrocytoma showed highrer expression of PD-L1 & IDH1 but with insignificant correlation (p=0.989). Conclusion: There is a relatively high expression of PD-L1 and IDH1 in patients with astrocytoma. More than half of the patients presented with MGMT promoter methylation. Further studies with larger sample size are required to investigate the association between these biomarkers and characteristics of patients with astrocytoma.     

GRP78 and CHOP modulate macrophage apoptosis and the development of bleomycin‐induced pulmonary fibrosis

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been associated with fibrotic lung disease, although exactly how they modulate this process remains unclear. Here we investigated the role of GRP78, the main UPR regulator, in an experimental model of lung injury and fibrosis. Grp78^+/?, Chop^?/? and wild type C57BL6/J mice were exposed to bleomycin by oropharyngeal intubation and lungs were examined at days 7 and 21. We demonstrate here that Grp78^+/? mice were strongly protected from bleomycin‐induced fibrosis, as shown by immunohistochemical analysis, collagen content and lung function measurements. In the inflammatory phase of this model, a reduced number of lung macrophages associated with an increased number of TUNEL‐positive cells were observed in Grp78^+/? mice. Dual immunohistochemical and in situ hybridization experiments showed that the macrophage population from the protected Grp78^+/? mice was also strongly positive for cleaved caspase‐3 and Chop mRNA, respectively. In contrast, the administration of bleomycin to Chop^?/? mice resulted in increased quasi‐static elastance and extracellular matrix deposition associated with an increased number of parenchymal arginase‐1‐positive macrophages that were negative for cleaved caspase‐3. The data presented indicate that the UPR is activated in fibrotic lung tissue and strongly localized to macrophages. GRP78‐ and CHOP‐mediated macrophage apoptosis was found to protect against bleomycin‐induced fibrosis. Overall, we demonstrate here that the fibrotic response to bleomycin is dependent on GRP78‐mediated events and provides evidence that macrophage polarization and apoptosis may play a role in this process. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Prevalence and clinical demographics of cerebral salt wasting in patients with aneurysmal subarachnoid hemorrhage

Hyponatremia is a frequent complication following subarachnoid hemorrhage (SAH), and is commonly attributed either to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome (CSW). The object of this study is to elucidate the clinical demographics and sequelae of hyponatremia due to CSW in subjects with aneurysmal SAH. Retrospective chart review of patients >18 years with aneurysmal SAH admitted between January 2004 and July 2007 was performed. Subjects with moderate to severe hyponatremia (serum sodium <130 mmol l⁻¹) were divided into groups consistent with CSW and SIADH based on urine output, fluid balance, natriuresis, and response to saline infusion. Clinical demographics were compared. Of 316 subjects identified, hyponatremia (serum sodium <135 mmol l⁻¹) was detected in 187 (59.2%) subjects and moderate to severe hyponatremia in 48 (15.2%). Of the latter group, 35.4% were categorized with SIADH and 22.9% with CSW. Compared to eunatremic subjects, hyponatremia was associated with significantly longer hospital stay (15.7 ± 1.9 vs. 9.6 ± 1.1 days, p < 0.001). Subjects with CSW had similar mortality and duration of hospital stay vs. those with SIADH. Though less common than SIADH, CSW was detected in approximately 23% of patients with history of aneurysmal SAH and was not clearly associated with enhanced morbidity and mortality compared to subjects with SIADH. Further studies regarding the pathogenesis and management, along with the medical consequences, of CSW are important.     

Venovenous versus venoarterial extracorporeal life support for pediatric respiratory failure: are there differences in survival and acute complications?

OBJECTIVES: To examine the Extracorporeal Life Support Organization (ELSO) registry database of infants and children with acute respiratory failure to compare outcome and complications of venovenous (VV) vs. venoarterial (VA) Extracorporeal Life Support (ECLS). DESIGN: Retrospective cohort study. SETTING: ELSO registry for pediatric pulmonary support. PATIENTS: All nonneonatal pediatric pulmonary support ECLS cases treated at U.S. centers and reported to the ELSO registry as of July 1997. Patients were excluded if they had one or more of the following diagnoses: hematologic-oncologic, cardiac, abdominal surgical, burn, metabolic, airway, or immunodeficiency disorder. INTERVENTIONS: Venoarterial or venovenous extracorporeal life support for severe pulmonary failure. MEASUREMENTS AND MAIN RESULTS: From 1986 to June of 1997, 763 pediatric patients met the inclusion criteria. Overall, 595 were initially managed with VA bypass, and 168 with VV bypass. The VA group was younger (mean +/- SD, 26.1+/-42.2 months for VA vs. 63.5+/-68.7 months for VV) and smaller (11.8+/-15.1 kg vs. 22.9+/-23.8 kg) (p<.001). There were no differences between groups in number of days on mechanical ventilation before ECLS, number of hours on ECLS, or number of hours on mechanical ventilation post-ECLS in survivors. Mean pH and Paco2 values, positive end-expiratory pressure, and mean airway pressure just before placing the patient on ECLS were also similar. VA-treated patients had higher Fio2 requirements (p = .034), lower Pao2 (p = .047), and lower Pao2/Fio2 ratio (p = .014) just before cannulation. There was a trend of higher peak inspiratory pressure in VA-treated patients (p = .053). Overall, survival rate was not different for the two groups (55.8% for VA vs. 60.1% for VV; p = .33). Central nervous system complications were not different between the two groups. Examination of the same variables was then conducted after dividing the patients into four subgroups. There were no significant differences in survival or complications during bypass between VV and VA modes of ECLS in any subgroup. Stepwise logistic regression modeling was performed to control for variables associated with the outcome survival for VV and VA-treated groups, and variables measured before bypass were identified as being associated with improved survival. There was a trend of improved survival in the VV-treated patients (p = .12). CONCLUSIONS: Overall survival of pediatric patients with acute respiratory failure supported by VA or VV ECLS was comparable. A randomized clinical trial may be useful in clarifying these observations.