Combined therapy with bevacizumab and photodynamic therapy for myopic choroidal neovascularization:A one-year follow-up controlled study

AIM: To evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizumab monotherapy.METHODS: Thirty-four eyes with angiographic evidence of myopic CNV were randomly divided into two groups:17 were treated with one intravitreal bevacizumab injection (1.25 mg) and low-fluence-rate PDT within seven days of the injection (Group A). The other 17 received monotherapy with bevacizumab injections (Group B). Clinical evidence of complications, best corrected visual acuity (BCVA) and fluorescein leakage were evaluated. BCVA and optical coherence tomography (OCT) were evaluated monthly. The timepoints follow-up was established at 6 and 12mo. All patients were retreated following a PRN protocol.RESULTS:A total of 34 eyes of 34 patients (26 women and 8 men) with a mean age of 62.35 years were included. In Group A (17 eyes) the mean BCVA increased from 0.55±0.13 logMAR before the treatment to 0.40±0.09 logMAR at the 12mo follow-up (P<0.01). In Group B (17 eyes) the mean BCVA increased from 0.60±0.11 logMAR before the treatment to 0.55±0.12 logMAR at the 12mo follow-up (P<0.01). There was no statistically significant difference between the two groups in terms of LogMar visual acuity. In Group A the mean number of combined treatments was 1.8±0.11 per patient; in Group B the mean number of intravitreal bevacizumab injections was 3.1±0.08 per patient. The number of treatments was significantly fewer in Group A (P<0.01). No local or systemic side effects occurred among any of the patients treated in this study.CONCLUSION:The combination of anti-angiogenic injections and PDT appears to be a safe and effective option for myopic CNV treatment and allows for a significant reduction of intravitreal injections.     

Downregulation of inflammatory markers by conjugated linoleic acid isomers in human cultured astrocytes

Objectives: Conjugated linoleic acid (CLA) isomers have been shown to possess anti-inflammatory activity in the central nervous system. In this study, we aimed to evaluate whether modulation of the fatty acid profile by the CLA isomers c9,t11 or t10,c12CLA was associated with changes in the expression of pro-inflammatory molecules in human astrocytes.

Methods: Cultured astrocytes were treated for 6 days with 100?µM fatty acids (c9,t11CLA or t10,c12CLA or oleic acid). Following the treatment, the fatty acid profile of the cell and pro-inflammatory molecule expression were assessed.

Results: Only the t10,c12CLA isomer induced a significant decrease in arachidonic acid and increased the ratio of docosahexaenoic acid/eicosapentaenoic acid, which constitutes indirect evidence of peroxisome proliferator-activated receptor alpha activation. Inhibition of tumour necrosis factor-α, interleukin-1β, and RANTES expression was observed in astrocytes treated with c9,t11CLA and t10,c12CLA.

Discussion: Current data demonstrate that CLA isomers, particularly t10,c12, may affect neuroinflammation by reducing the pro-inflammatory molecules in cultured astrocytes, suggesting a potential nutritional role of CLA isomers in modulating the astrocyte inflammatory response.     

Healthcare utilization following spinal cord injury: Objective findings from a regional hospital registry

Objective: The purpose was to describe the prevalence and characteristics of healthcare utilization among individuals with spinal cord injury (SCI) from a Level I trauma center.

Design: Retrospective data analysis utilizing a local acute trauma registry for initial hospitalization and merged with the Dallas-Fort Worth Hospital Council registry to obtain subsequent health care utilization in the first post-injury year.

Setting: Dallas, TX, USA.

Participants: Six hundred and sixty four patients were admitted with an acute traumatic SCI from January 2003 through June 2014 to a Level I trauma center. Fifty five patients that expired during initial hospitalization and 18 patients with unspecified SCI (defined by ICD-9 with no etiology or level of injury specified) were not included in the analysis, leaving a final sample of 591.

Outcome Measures: Data included demographic and clinical characteristics, charges, and healthcare utilization.

Results: Mean age was 46.1?years (±18.9?years), the majority of patients were male (74%), and Caucasian (58%). Of the 591 patients, 345 (58%) had additional inpatient or emergency healthcare utilization accounting for 769 additional visits (median of 3 visits per person). Of the 769 encounters, 534 (69%) were inpatient and 235 (31%) were emergency visits not resulting in an admission. The most prevalent ICD-9 codes listed were pressure ulcer, neurogenic bowel, neurogenic bladder, urinary tract infection, fluid electrolyte imbalance, hypertension, and tobacco use.

Conclusion: Individuals with SCI experience high levels of healthcare utilization which are costly and may be preventable. Increasing our understanding of the prevalence and causes for healthcare utilization after acute SCI is important to target preventive strategies.     

The outcome measures for loss of functionality in the activities of daily living of adults after stroke: a systematic review

Objective: To provide clinicians and researchers information regarding (1) the existing outcome measures to assess the loss of functionality in the activities of daily living (ADLs) of patients with stroke and (2) the presence of these assessment tools in the Italian context.

Study Design and Setting: For this Systematic Review Medline, CINAHL, and PsycINFO were searched for articles published up to 4 July 2017. Two authors independently identified eligible studies on the basis of prede?ned inclusion criteria and extracted data. Study quality and risk of bias were assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

Results: Of 370 publications identified and screened, 46 studies fell within the inclusion criteria and were critically reviewed. The most commonly used tools were: the Frenchay Activities Index and the Functional Independence Measure.

Conclusion: This review has emphasized the need for agreement among researchers as to which tool must be studied in depth or adapted to other national contexts in order to develop universal norms and standards.     

Efficacy and safety of pegylated liposomal doxorubicin in primary cutaneous B‐cell lymphomas and comparison with the commonly used therapies

Objectives: The therapy of advanced, relapsed or refractory primary cutaneous lymphomas is often unsatisfactory. Recent data indicate a favourable pharmacokynetic, pharmacodynamic and toxicity profile of pegylated liposomal doxorubicin (Peg‐Doxo) in primary cutaneous T‐cell lymphomas, while in primary cutaneous B‐cell lymphomas (PCBCLs), the drug efficacy has never been assessed so far. Methods: We performed a prospective phase II pilot clinical trial of Peg‐Doxo monotherapy (20 mg/m²) in PCBCLs. One patient had a marginal zone B‐cell lymphoma and four were affected by diffuse large B‐cell lymphoma‐leg type, all with widespread nodular lesions. Results: All the patients achieved a complete response (CR = 100%) in a short period of time (median 3 months), even when pretreated with radio‐chemotherapy. Two experienced a relapse. At follow‐up, one patient died for progressive disease; four are in CR after 5, 52, 63 and 69 months. As concerning the toxicity profile, the treatment was well‐tolerated, no one decreased or delayed the dose. The haematological toxicity was mild with only one case of grade III neutropenia; a patient showed a grade I neurotoxicity. Dermatological toxicity, in particular the palmar–plantar erythrodysesthesia, did not occurred, probably because of both the low dosages of Peg‐Doxo monotherapy and the oral prophylaxis with pyridoxine. Conclusions: In spite of the small number of patients, it emerges that monochemotherapy with Peg‐Doxo has a significantly high clinical activity and a good safety profile in PCBCLs, even in aggressive forms, compared with other therapeutic regimens, which are completely reviewed. It suggests the need of further investigations in this field.     

Gestación gemelar con feto muerto intraútero en el segundo trimestre

Nowadays, twin gestation is increased due to advances in assisted reproduction. Unquestionably, these pregnancies have an increased risk of foetal and maternal disorders. Single foetal death has a different incidence depending on gestational age; in the first trimester between 10-70%, in the second and third trimester it is a rare event, 0.5-7%.     

Further insight on the hypoglycemic and nonhypoglycemic effects of troglitazone 400 or 600 mg/d: effects on the very-low-density and high-density lipoprotein particle distribution.

The effects of troglitazone 400 or 600 mg/d on the glycemic control, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) subclass concentrations and plasminogen-activator inhibitor 1 (PAI-1) levels were assessed in patients with type 2 diabetes that had not been controlled with dietary treatment. This was a multicenter, open-label, parallel-groups study. It included a run-in 4-week diet period and a 24-week randomized treatment. Fifty one patients received 400 mg/d and 55 patients 600 mg. The mean HbA(1c) concentration at the end of the study was similar for both doses. Troglitazone, regardless of dose, significantly improved insulin sensitivity assessed by the homeostasis model (HOMA). PAI-1 levels were significantly decreased in both groups by 13%. Higher HDL cholesterol concentrations and lower triglycerides levels were observed at the end of treatment. Triglyceride contents were reduced only in the lighter VLDL1. The change in HDL cholesterol concentration resulted from a combination of increased HDL3 cholesterol and lower HDL2 cholesterol levels. No differences were found in the effects of both treatment groups on the evaluated parameters. Our data provide new information about the actions of the drug on the lipid profile. Troglitazone reduces triglyceride levels by lowering the triglycerides content of the VLDL1 particles and increases HDL cholesterol concentrations by increasing HDL3 cholesterol levels.     

The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta-analysis.

OBJECTIVES: The purpose of this work was to determine the prognostic value of normal exercise myocardial perfusion imaging (MPI) tests and exercise echocardiography tests, and to determine the prognostic value of these imaging modalities in women and men. BACKGROUND: Exercise MPI and exercise echocardiography provide prognostic information that is useful in the risk stratification of patients with suspected coronary artery disease (CAD). METHODS: We searched the PubMed, Cochrane, and DARE databases between January 1990 and May 2005, and reviewed bibliographies of articles obtained. We included prospective cohort studies of subjects who underwent exercise MPI or exercise echocardiography for known or suspected CAD, and provided data on primary outcomes of myocardial infarction (MI) and cardiac death with at least 3 months of follow-up. Secondary outcomes (unstable angina, revascularization procedures) were abstracted if provided. Studies performed exclusively in patients with CAD were excluded. RESULTS: The negative predictive value (NPV) for MI and cardiac death was 98.8% (95% confidence interval [CI] 98.5 to 99.0) over 36 months of follow-up for MPI, and 98.4% (95% CI 97.9 to 98.9) over 33 months for echocardiography. The corresponding annualized event rates were 0.45% per year for MPI and 0.54% per year for echocardiography. In subgroup analyses, annualized event rates were <1% for each MPI isotope, and were similar for women and men. For secondary events, MPI and echocardiography had annualized event rates of 1.25% and 0.95%, respectively. CONCLUSIONS: Both exercise MPI and exercise echocardiography have high NPVs for primary and secondary cardiac events. The prognostic utility of both modalities is similar for both men and women.     

Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients

BACKGROUND: The pathophysiologic mechanisms that determine the severity of Mediterranean spotted fever (MSF) and the host-related and microbe-related risk factors for a fatal outcome are incompletely understood. METHODS: This prospective study used univariate and multivariate analyses to determine the risk factors for a fatal outcome for 140 patients with Rickettsia conorii infection admitted to 13 Portuguese hospitals during 1994-2006 with documented identification of the rickettsial strain causing their infection. RESULTS: A total of 71 patients (51%) were infected with the Malish strain of Rickettsia conorii, and 69 (49%) were infected with the Israeli spotted fever (ISF) strain. Patients were admitted to the intensive care unit (40 [29%]), hospitalized as routine inpatients (95[67%]), or managed as outpatients (5[4%]). Death occurred in 29 adults (21%). A fatal outcome was significantly more likely for patients infected with the ISF strain, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, obtundation and/or confusion, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated levels of hepatic enzymes and creatine kinase. Some, but not all, of these findings were observed more often in ISF strain-infected patients. CONCLUSIONS: Although fatalities and similar clinical manifestations occurred among both groups of patients, the ISF strain was more virulent than the Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.