High cut-off hemofiltration versus standard hemofiltration: a pilot assessment of effects on indices of apoptosis.

OBJECTIVES: To measure plasma pro-apoptotic and pro-necrotic activity in severe acute kidney injury (AKI) patients within a randomized controlled trial of continuous veno-venous hemofiltration with high cut-off filters (CVVH-HCO) versus standard filters (CVVH-Std). METHODS: We measured pro-apoptotic and pro-necrotic plasma activity by trypan blue exclusion cell viability assay, detection of DNA fragmentation, and by determination of caspase-3 activity and annexin V-based apoptosis and necrosis detection assay. RESULTS: Compared to no apoptosis or necrosis after incubation with healthy plasma, 14-18% of cells showed apoptosis and 4-8% showed necrosis after incubation with plasma from AKI patients. When comparing different measures of pro-apoptotic or pro-necrotic activity, CVVH-HCO and CVVH-Std showed no differential effects on such activity, which remained high over the first 3 days of treatment. However, using annexin V-FITC, there was a significant drop in pro-apoptotic activity across the filter for the CVVH-HCO group (p = 0.043) but not for the CVVH-Std group (p = 0.327) and a significant difference between the two groups (CVVH-HCO vs. CVVH-Std p = 0.006). CONCLUSIONS: Patients with severe AKI have increased pro-apoptotic and pro-necrotic activity. Although on single-pass effect assessment, CVVH-HCO was superior to CVVH-Std in decreasing annexin V-FITC-assessed pro-apoptotic activity, there was no overall attenuation of such activity during the first 3 days of treatment.

Potential of dihydropyrimidine dehydrogenase genotypes in personalizing 5-fluorouracil therapy among colorectal cancer patients.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine. METHODS: A total of 26 patients comprising 3 different ethnic groups (Malay, Chinese, and Indian) diagnosed with colorectal cancer and treated with 5-FU chemotherapy regimen from local hospital were recruited. Polymerase chain reaction and denaturing high-performance liquid chromatography methods were developed to screen polymorphisms of DPYD gene. High-performance liquid chromatography-based quantification assay was developed to measure the serum concentration of 5-FU among these patients. RESULTS: Patients with DPYD genotypes of deficient enzyme activity had higher median serum levels of 5-FU compared with normal DPD group (median, 11.51 mcg/mL; 95% confidence interval, 10.18-16.11 versus median, 0.83 mcg/mL; 95% confidence interval, 0.55-5.90, Mann-Whitney U test; P = 0.010). Patients with neutropenia (n = 11) had significantly higher serum concentrations of 5-FU as compared with those with normal white blood cell count (n = 15) (Mann-Whitney U test, P = 0.031). Combined regression analysis showed that the predictive power of DPYD*5 (rs1801159) and 1896 T>C (rs17376848) for serum concentrations of 5-FU in the studied group was 36.6% (P = 0.04). Similarly, DPYD*5 and 1896 T>C accounted for 29.9% of the occurrences of neutropenia (analysis of variance, P = 0.017). CONCLUSIONS: This study revealed that DPYD*5 (rs1801159) and 1896 T>C (rs17376848) are potentially useful predictive markers of patients' responses to 5-FU chemotherapy. Pharmacogenotyping is therefore recommended to guide dosing of 5-FU and prevent neutropenia.

Association between Appendectomy and Demyelinating Disorders in Subjects 40 Years and Older.

BACKGROUND: The association between appendectomy and multiple sclerosis (MS) is unknown. In this study, we explored the association between appendectomy and MS and neuromyelitis optica spectrum disorder (NMOSD). PATIENTS AND METHODS: MS and NMOSD patients older than 40 were identified from neurology records from hospitals in Malaysia. The diagnoses were based on the Revised McDonald (2010) and Wingerchuk (2015) criteria. Controls were sampled from Malaysia's normal population. Individuals were interviewed telephonically or face-to-face. The age inclusion criterion (over 40) differentiated high or low lifetime risk of appendicitis, as appendicitis incidence is rare after 40. RESULTS: 49 MS, 71 NMOSD, and 880 controls met the inclusion criteria. Seventy-two individuals (9 MS, 4 NMOSD, 59 control) had undergone appendectomy. Appendectomy rates were 18.37% in the MS group (95% CI 7.5-29.2%), 5.6% in the NMOSD group (0.3%, 11%), and 6.7% among controls (5.1%, 8.4%), (MS vs NMOSD P = 0.036, MS vs controls P = 0.007). Binary regression analysis showed that MS was an independent risk factor for appendectomy (OR 2.938, 95% CI 1.302, 6.633, P = 0.009). NMOSD showed no association with appendectomy. CONCLUSION: MS is positively associated with appendectomy, unlike ulcerative colitis, which is negatively associated. We hypothesize that there is a commonality in the microflora in persons who have had these two illnesses.

Sensitivity and specificity of automated analysis of single-field non-mydriatic fundus photographs by Bosch DR Algorithm-Comparison with mydriatic fundus photography (ETDRS) for screening in undiagnosed diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Early diagnosis through effective screening programs is likely to improve vision outcomes. The ETDRS seven-standard-field 35-mm stereoscopic color retinal imaging (ETDRS) of the dilated eye is elaborate and requires mydriasis, and is unsuitable for screening. We evaluated an image analysis application for the automated diagnosis of DR from non-mydriatic single-field images. Patients suffering from diabetes for at least 5 years were included if they were 18 years or older. Patients already diagnosed with DR were excluded. Physiologic mydriasis was achieved by placing the subjects in a dark room. Images were captured using a Bosch Mobile Eye Care fundus camera. The images were analyzed by the Retinal Imaging Bosch DR Algorithm for the diagnosis of DR. All subjects also subsequently underwent pharmacological mydriasis and ETDRS imaging. Non-mydriatic and mydriatic images were read by ophthalmologists. The ETDRS readings were used as the gold standard for calculating the sensitivity and specificity for the software. 564 consecutive subjects (1128 eyes) were recruited from six centers in India. Each subject was evaluated at a single outpatient visit. Forty-four of 1128 images (3.9%) could not be read by the algorithm, and were categorized as inconclusive. In four subjects, neither eye provided an acceptable image: these four subjects were excluded from the analysis. This left 560 subjects for analysis (1084 eyes). The algorithm correctly diagnosed 531 of 560 cases. The sensitivity, specificity, and positive and negative predictive values were 91%, 97%, 94%, and 95% respectively. The Bosch DR Algorithm shows favorable sensitivity and specificity in diagnosing DR from non-mydriatic images, and can greatly simplify screening for DR. This also has major implications for telemedicine in the use of screening for retinopathy in patients with diabetes mellitus.

The impact factor of an open access journal does not contribute to an article's citations.

Background Citations of papers are positively influenced by the journal's impact factor (IF). For non-open access (non-OA) journals, this influence may be due to the fact that high-IF journals are more often purchased by libraries, and are therefore more often available to researchers, than low-IF journals. This positive influence has not, however, been shown specifically for papers published in open access (OA) journals, which are universally accessible, and do not need library purchase. It is therefore important to ascertain if the IF influences citations in OA journals too. Methods 203 randomized controlled trials (102 OA and 101 non-OA) published in January 2011 were included in the study. Five-year citations for papers published in OA journals were compared to those for non-OA journals. Source papers were derived from PubMed. Citations were retrieved from Web of Science, Scopus, and Google Scholar databases. The Thompson-Reuter's IF was used. Results OA journals were found to have significantly more citations overall compared to non-OA journals (median 15.5 vs 12, p=0.039). The IF did not correlate with citations for OA journals (Spearman's rho =0.187, p=0.60). The increase in the citations with increasing IF was minimal for OA journals (beta coefficient = 3.346, 95% CI -0.464, 7.156, p=0.084). In contrast, the IF did show moderate correlation with citations for articles published in non-OA journals (Spearman's rho=0.514, p<0.001). The increase in the number of citations was also significant (beta coefficient = 4.347, 95% CI 2.42, 6.274, p<0.001). Conclusion It is better to publish in an OA journal for more citations. It may not be worth paying high publishing fees for higher IF journals, because there is minimal gain in terms of increased number of citations. On the other hand, if one wishes to publish in a non-OA journal, it is better to choose one with a high IF.

Cellular events and biomarkers of wound healing.

Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs) and the tissue inhibitors of these metalloproteinases (TIMPs). MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds.

Recurrent furunculosis as a cause of isolated penile lymphedema: a case report.

INTRODUCTION: Isolated lymphedema of the penis is extremely rare: combined involvement of the scrotum and penis is the norm. Furunculosis as a cause is not, to our knowledge, previously reported. We present a case of isolated penile lymphedema that responded to excision of lymphedematous tissue and reconstruction with flaps. CASE PRESENTATION: A 32-year-old Arab man presented with a three-year history of a gradually increasing, painless penile swelling. Our patient's main complaint was non-erectile sexual dysfunction. The swelling was preceded by at least three prior episodes of severe furunculosis at the penile root. He had no other contributory past medical or family history. On examination there was gross penile enlargement, maximally at the mid shaft, associated with thickened skin at the sites of prior furunculosis. The glans and scrotum were normal. Both testes were palpable. Serology for filariasis, and urinary tract ultrasound and computed tomography scan were normal. The clinical diagnosis was lymphedema following recurrent penile furunculosis. At operation the lymphedematous tissues were removed. Closure of the penile shaft was accomplished by bilateral advancement of flaps from both ends of the penis. He resumed normal sexual activity one month after surgery. At 12 months, he had a good cosmetic result, with no signs of recurrence. CONCLUSIONS: Furunculosis at the penile root may result in lymphedema confined to the penile shaft, sparing the scrotum. Excision of abnormal tissue and cover with a skin flap gave excellent cosmetic results, and allowed satisfactory sexual activity.