Clinical benefits of routine examination and synchronous repair of occult inguinal hernia during laparoscopic peritoneal dialysis catheter insertion: a single-center experience.

PURPOSE: Occult inguinal hernias (IH) predispose peritoneal dialysis (PD) patients to the symptomatic IH formation after starting PD, which may cause complications. We conducted a retrospective study to assess the benefit/risk profile of routine laparoscopic examination for occult IH (RLEOH) with a synchronous repair in patients receiving PD catheter placement. METHODS: 432 patients were enrolled in this study. Patients with an internal hernia sac at all sizes were deemed to have occult IH. We retrospectively reviewed data including demographic characteristics and operative details. We also measured incidence rates of symptomatic IH, metachronous IH repair, and catheter survival over a follow-up period after starting PD. RESULTS: These patients were classified into the RLEOH group (n = 365) and the non-RLEOH group (n = 67). The RLEOH group was subdivided into occult IH with a synchronous repair (n = 17; the subgroup A), no occult IH (n = 339; the subgroup B), and occult IH without a synchronous repair (n = 9; the subgroup C). The incidence rates of symptomatic IH developed after staring PD in subgroups A, B, and C were 0, 5.6, and 22.2%, respectively, whereas that in the non-RLEOH group was 13.4%. The RLEOH group had a reduced hazard ratio for metachronous IH repair compared with the non-RLEOH group (HR = 0.426; 95% CI 0.195-0.930, p = 0.032). None of our patients suffered from herniorrhaphy-related complications. CONCLUSION: RLEOH with a synchronous repair during PD catheter insertion confers clinical benefits in reducing the risk of developing IH after starting PD and the need for a metachronous repair. This is a safe and reasonable approach.

Downstream changes in river avulsion style are related to channel morphology.

One of the most dramatic events in river environments is the natural diversion, or avulsion, of a channel across its floodplain. Though rarely witnessed, avulsions can cause massive floods, and over geologic time they create most of the fluvial stratigraphic record. Avulsions exhibit behavior ranging from reoccupying abandoned channels to constructing new channels and splay complexes. To quantify avulsion behavior, or style, we measure avulsion-related floodplain disturbance in modern environments. We show that for 63 avulsions from Andean, Himalayan, and New Guinean basins, avulsion style correlates with channel morphology and changes systematically downstream. Avulsions in braided rivers reoccupy abandoned channels, whereas avulsions in meandering rivers often produce flooding and sediment deposition during channel construction. These downstream changes in avulsion style can explain the abrupt transition from channel-dominated to floodplain-dominated facies commonly observed in foreland basin stratigraphy. These dynamics also explain why some avulsions are more hazardous than others.

Simultaneous regeneration of calcium lactate and cellulose into PCL nanofiber for biomedical application.

Synthetic polymers are easy to process and have excellent mechanical properties but low wettability and poor cell compatibility limit their applications in tissue scaffolding. In this study, a facile procedure was established to regenerate cellulose and calcium lactate (CaL) into a polycaprolactone (PCL) nanofibrous scaffold for tissue engineering applications. Briefly, varying amounts of lactic acid (LA) was mixed with the blend of PCL and cellulose acetate (CA) solutions and electrospun to fabricate an optimal composite PCL/CA/LA fibrous membrane. Later on, as-prepared membranes were treated with calcium hydroxide solution. This process simultaneously converted CA and LA contents into Cellulose and CaL, respectively. In situ regeneration of Cellulose and CaL into the composite fiber remarkably enhanced the biological and physicochemical properties of the composite fiber. This work provides a novel dual-channel strategy for simultaneous regeneration of biopolymer and bioactive molecule into the PCL nanofiber for regenerative medicine and tissue engineering applications.

Spleen-preserving versus spleen-sacrificing distal pancreatectomy in adults with blunt major pancreatic injury.

BACKGROUND: The aim of this study was to analyse outcomes of spleen-preserving (SPDP) and spleen-sacrificing (SSDP) distal pancreatectomy in adults with severe blunt pancreatic injuries. METHODS: This was an observational study of adult patients who underwent distal pancreatectomy for grade III or IV blunt pancreatic injury between 1991 and 2015. Outcomes of SPDP and SSDP were compared. RESULTS: Fifty-one patients were included, of whom 23 underwent SPDP and 28 SSDP. The median Injury Severity Score (ISS) was 13·0 (i.q.r. 9·0-18·0). No significant differences were observed between the groups regarding sex, trauma mechanism, shock at triage, laboratory data, location, ISS, associated injury, length of stay, mortality or morbidity. Age (27·0 versus 36·5 years; P = 0·012) and time interval from injury to distal pancreatectomy (15·0 versus 44·0 h; P = 0·022) differed significantly between SPDP and SSDP groups respectively. The mortality rate was 4 per cent (1 of 23) versus 11 per cent (3 of 28) respectively (P = 0·617). Nine patients (39 per cent) developed abdominal morbidity after SPDP, compared with 17 (61 per cent) after SSPD (P = 0·125). In the SPDP group, eight patients had grade B postoperative pancreatic fistula (POPF), two of whom required further intervention. In the SSDP group, six of ten patients with grade B POPF required CT-guided drainage, and a further five patients required reoperation for other causes. There were more reinterventions after SSDP: 11 of 28 (39 per cent) versus 3 of 23 (13 per cent) in the SPDP group (P = 0·037). CONCLUSION: SPDP was performed more often in younger patients and at a shorter interval after severe blunt pancreatic injury. SPDP was associated with fewer reinterventions.

Prediction of radiographic abnormalities by the use of bag-of-features and convolutional neural networks.

This study evaluated the feasibility of bag-of-features (BOF) and convolutional neural networks (CNN) for computer-aided detection in distinguishing normal from abnormal radiographic findings. Computed thoracic radiographs of dogs were collected. For the purposes of this study, radiographic findings were used to distinguish between normal and abnormal in the following areas: (1) normal cardiac silhouette vs. cardiomegaly, (2) normal lung vs. abnormal lung patterns, (3) normal mediastinal position vs. mediastinal shift, (4) normal pleural space vs. pleural effusion, and (5) normal pleural space vs. pneumothorax. Images for training and testing the models consisted of ventrodorsal and lateral projection images of the same scale. The number of images used for each finding are as follow: 3142 for cardiomegaly (1571 normal and 1571 abnormal from 1143 dogs), 2086 for lung pattern (1043 normal and 1043 abnormal from 1247 dogs), 892 for mediastinal shift (446 normal and 446 abnormal from 387 dogs), 940 for pleural effusion (470 normal and 470 abnormal from 284 dogs), and 78 for pneumothorax (39 normal and 39 abnormal from 61 dogs). All data samples were divided so that 60% would be used for training the algorithms and 40% for testing the two models. The performance of the classifiers was evaluated by calculating the accuracy, sensitivity and specificity. The accuracy of both models ranged from 79.6% to 96.9% in the testing set. CNN showed higher accuracy (CNN; 92.9-96.9% and BOF; 79.6-96.9%) and sensitivity (CNN; 92.1-100% and BOF; 74.1-94.8%) than BOF. In conclusion, both BOF and CNN have potential to be useful for improving work efficiency by double reading.

Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: The first evidence.

OBJECTIVES: Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis. METHODS: CK13 and CK17 expressions were evaluated using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterisation of CK17 expression with respect to its ability in predicting metastatic disease, an in vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed using a serial statistical method. RESULTS: CK13 was predominately expressed in non-cancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P < .0001) in an in vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan-Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P < .05) with 10-year follow-up. CONCLUSION: Our findings provide the first evidence that CK17 under-expression might be a potential predictor of nodal metastasis and adverse prognosis.

Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia.

Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC-derived susceptibility variants. Schizophrenia PRS at the P-value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han-Taiwanese samples, and the score itself had a P-value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.

Challenges in the Development of Novel Cardiovascular Therapies.

Cardiovascular disease accounts for nearly one in three deaths globally, but few novel therapies have reached patients and clinicians in recent years. This translational report reviews trends in the development and approval of cardiovascular drugs and evaluates recent innovation in the field of cardiovascular disease therapeutics. New policies are needed to better support the development of safe and effective therapies with the greatest potential to improve patient health outcomes.

Effect of US Food and Drug Administration's Cardiovascular Safety Guidance on Diabetes Drug Development.

In 2008, the US Food and Drug Administration (FDA) issued guidance on the need for cardiovascular outcome trials to assess the safety of new diabetes medications. Using two large commercial databases, we evaluated the effect of the FDA's cardiovascular safety guidance on drug development for type 2 diabetes as well as a comparison group of drugs intended to treat other alimentary and metabolic conditions. The FDA's guidance was associated with a 31% differential decrease in the rate of diabetes drugs entering phase II trials, but the remaining drugs were significantly more likely to target novel biological pathways (72% of drugs had novel mechanisms after the guidance vs. 49% before the guidance). No differential changes were observed for phase I and phase III trials. There was no measurable improvement during the study period in glycemic efficacy among investigational products entering phase III trials. This research highlights how regulatory actions can impact pharmaceutical innovation.

Radiologist performance in the interpretation of contrast enemas performed for Hirschsprung's disease in children >1 year of age.

AIM: To evaluate the diagnostic performance of contrast enemas (CEs) for the diagnosis of Hirschsprung's disease (HD). METHODS AND MATERIALS: CE studies performed as part of an HD workup in patients 1-18 years of age over a 10-year period were identified. All abnormal CE studies and an equal number of age-matched controls were included in the final study group. Two radiologists independently and blindly reviewed all CE studies for quality (scale of 0-3) and the presence of large colon calibre, colon redundancy, transition zone, rectosigmoid ratio, and abnormal contractions. Readers also determined whether a rectal biopsy would be recommended to confirm an HD diagnosis. Discrepancies were resolved in consensus. Findings were correlated with surgery and biopsy data. RESULTS: Out of 834 CE studies, 38 abnormal CE studies were identified (mean age 5.9 years) and included 38 matched controls. Seventeen of 76 patients were recommended for rectal biopsy, of which five were confirmed to have HD. Twelve of 70 (17.1%) were false positives, and were clinically confirmed not to have HD. The proportion of HD in the present population was 6/834 (0.72%). Of the 17 recommended for biopsy, CE studies showed 17/17 (100%) with an abnormal rectosigmoid ratio, 16/17 (94.1%) with redundant colon, and 15/17 (88%) with large colon. Of patients not recommended for biopsy, one was diagnosed with HD, (false negative, 16.7%). The diagnostic performance of CE was 83.3% sensitivity and 82.9% specificity. CONCLUSION: Few children >1 year of age were found to have HD and the diagnostic performance of the CE is moderately high. The CE examination is a valuable non-invasive imaging study to help exclude older children who may not have HD, thereby obviating the need for invasive rectal biopsy and surgery.

Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography.

Optical coherence tomography angiography (OCTA) is a noninvasive method of 3D imaging of the retinal and choroidal circulations. However, vascular depth discrimination is limited by superficial vessels projecting flow signal artifact onto deeper layers. The projection-resolved (PR) OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers. This novel technology allowed us to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Our investigation in normal human volunteers revealed the presence of 2 to 4 distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers are consistent with previous histologic studies. Based on these data, we propose an improved system of nomenclature and segmentation boundaries for detailed 3-dimensional retinal vascular anatomy by OCTA. This could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion, and neovascularization.

Aberrant expression of microRNAs as biomarker for schizophrenia: from acute state to partial remission, and from peripheral blood to cortical tissue.

Based on our previous finding of a seven-miRNA (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) signature as a potential biomarker for schizophrenia, this study aimed to examine if hospitalization could affect expressions of these miRNAs. We compared their expression levels between acute state and partial remission state in people with schizophrenia (n=48) using quantitative PCR method. Further, to examine whether the blood and brain show similar expression patterns, the expressions of two miRNAs (hsa-miR-34a and hsa-miR-548d) were examined in the postmortem brain tissue of people with schizophrenia (n=25) and controls (n=27). The expression level of the seven miRNAs did not alter after ~2 months of hospitalization with significant improvement in clinical symptoms, suggesting the miRNAs could be traits rather than state-dependent markers. The aberrant expression seen in the blood of hsa-miR-34a and hsa-miR-548d were not present in the brain samples, but this does not discount the possibility that the peripheral miRNAs could be clinically useful biomarkers for schizophrenia. Unexpectedly, we found an age-dependent increase in hsa-miR-34a expressions in human cortical (Brodmann area 46 (BA46)) but not subcortical region (caudate putamen). The correlation between hsa-miR-34a expression level in BA46 and age was much stronger in the controls than in the cases, and the corresponding correlation in the blood was only seen in the cases. The association between the miRNA dysregulations, the disease predisposition and aging warrants further investigation. Taken together, this study provides further insight on the candidate peripheral miRNAs as stable biomarkers for the diagnostics of schizophrenia.

Semi-quantitative HPV viral load in patients with ASC-US cytology: viral load correlates strongly with the presence of CIN but only weakly with its severity.

OBJECTIVES: This study was performed to evaluate the prognostic significance of human papillomavirus (HPV) viral load, expressed in relative light units (RLUs), in patients with atypical squamous cells of undetermined significance (ASC-US) cytology. METHODS: A total of 349 ASC-US cases with HPV infection, detected using Hybrid Capture 2, were diagnosed histologically. A colposcopically directed punch biopsy was performed on acetowhite areas. Endocervical curettage biopsy and random cervical punch biopsy in four quadrants were performed in unsatisfactory colposcopy cases. In negative colposcopy cases, random cervical punch biopsy in four quadrants was performed. RESULTS: Case with no cervical intraepithelial neoplasia (CIN), CIN1 and CIN2+ (CIN2/CIN3) accounted for 162, 135 and 52 cases, respectively. The mean age showed no difference among the three groups (P = 0.510). There was a significant correlation between RLU values and the presence of CIN (P < 0.001), but less so with its severity: the median RLU values for negative, CIN1 and CIN2+ cases were 42.68, 146.45 and 156.43, respectively, with widely overlapping confidence intervals. The cut-off values of RLU to detect CIN1+ and CIN2+ were 6.73 and 45.64, respectively. CONCLUSIONS: The HPV viral load in ASC-US cases showed a significant correlation with the presence of CIN and less so with its severity, and showed large overlap of viral loads between grades of CIN. In ASC-US cases, RLU was not an accurate predictor of immediate high-grade CIN.

Prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma.

AIM: In this study, we investigated the prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma (GC). PATIENTS AND METHODS: A total of 1194 node-positive and 1030 node-negative GC patients undergoing potentially curative gastrectomy was enrolled in this study. Patients were stratified into 3 groups according to the number of examined lymph nodes: group 1, ≤ 15; group 2, 16-25; group 3, >25. RESULTS: Patients with node-negative GC had significantly favorable survival compared with those with node-positive. Among patients with node-negative T2-T4 disease, the percentage of locoregional relapse was higher in those with <25 examined lymph nodes than in those with ≥ 25 examined lymph nodes. The number of examined lymph nodes affected the overall survival rates for patients with node-negative T2-T4 GC but not for patients with T1 lesions. Tumor size, tumor location, the number of examined lymph nodes, T status, and the presence of perineural invasion were significant prognostic factors as determined by multivariate analysis in node-negative GC. CONCLUSIONS: No survival benefit of examining ≥ 15 lymph nodes was noted for patients with node-negative T1 GC. Extensive lymphadenectomy in patients with node-negative T2-T4 lesions in whom the number of examined lymph nodes was >25 had favorable survival.

Impact of personality and depression on quality of life in patients with severe haemophilia in Korea.

Among reports on the psychological variables that influence quality of life (QoL), none has addressed the impact of personality on QoL in patients with haemophilia. We investigated the impact of psychosocial variables including depression and personality on QoL in patients with severe haemophilia. A cross-sectional survey examining psychosocial and clinical characteristics was administered to Korean patients with severe haemophilia. Personality traits were ascertained using the 10-item short version of the Big Five Inventory, which quantifies five personality dimensions including extraversion, agreeableness, conscientiousness, neuroticism and openness. Patient QoL and depression were measured by the World Health Organization Quality of Life-abbreviated version and the Beck Depression Inventory (BDI) respectively. Multivariate linear regression analyses were used for each domain to determine the impact of psychological variables on QoL. Of the 53 subjects who consented to participate, 46 cases were finally analysed. Multivariate linear regression analyses demonstrated that agreeableness was significantly and positively associated with the physical health domain of QoL. Openness was independently and positively associated with the psychological and social relationship domains of QoL. BDI scores were significantly and negatively associated with all four domains of the QoL. Persistent pain and joint impairment showed strong associations with all domains in a univariate analysis, but the impact was attenuated after adjusting for psychosocial variables. Personality and depression had strong impacts on QoL independent of physical status in patients with severe haemophilia. Providing psychological screening and intervention are recommended for enhancing QoL in patients with severe haemophilia.

Safety of cycloserine and terizidone for the treatment of drug-resistant tuberculosis: a meta-analysis.

Although cycloserine (CS) is recommended by the World Health Organization as a second-line agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), safety concerns have impeded its uptake by several national TB programmes. Terizidone (TRD), a structural analogue of cycloserine, may be better tolerated. To assess the safety of CS and TRD for TB treatment, a systematic review and meta-analysis were conducted. From articles published up to December 2011, 27 studies with 2164 patients were included in our review of CS use. The pooled estimate for the frequencies of any adverse drug reaction (ADR) from CS was 9.1% (95%CI 6.4-11.7); it was 5.7% (95%CI 3.7-7.6) for psychiatric ADRs, and 1.1% (95%CI 0.2-2.1) for central nervous system (CNS) related ADRs. TRD showed no better to moderately better safety than CS in a systematic review of the available literature. The published evidence suggests that CS is associated with a higher frequency of psychiatric and CNS-related ADRs than other second-line drugs. While data were limited, treatment discontinuation rates appeared to be manageable. There were no significant differences in tolerability by region, study period or combination. As countries review and revise their treatment programmes, CS, and potentially TRD, should be included in MDR-TB treatment regimens. Adequate information on possible ADRs should be provided to patients, their families and attending health care workers. Greater attention to MDR-TB patients' mental health and a significant increase in resources devoted to pharmacovigilance and treatment of MDR-TB are essential.

Association of glypican-4 with body fat distribution, insulin resistance, and nonalcoholic fatty liver disease.

CONTEXT AND OBJECTIVE: Glypican-4 was identified as a novel adipokine capable of enhancing insulin signaling and modulating adipocyte differentiation. We investigated associations between glypican-4 and body composition, insulin resistance, arterial stiffness, and nonalcoholic fatty liver disease (NAFLD) in nondiabetic Asian subjects. DESIGN AND PARTICIPANTS: We analyzed baseline cross-sectional data from the Korean Sarcopenic Obesity Study, an ongoing prospective cohort study. NAFLD was diagnosed by unenhanced computed tomography using the liver attenuation index. We also examined the effects of a 3-month combined aerobic and resistance exercise program on glypican-4 levels and cardiometabolic risk factors. RESULTS: Circulating glypican-4 levels were higher in men than in women (1.83 [1.19, 2.78] ng/mL vs 1.17 [0.66, 2.00] ng/mL, P < .001) and had a significant positive relationship with the waist-to-hip ratio (WHR) (r = 0.20, P = .014) and the ratio of visceral to sc fat area (r = 0.30, P < .001). Furthermore, glypican-4 levels in women were correlated with cardiometabolic risk factors, including insulin resistance and arterial stiffness, and were independently associated with NAFLD by multiple logistic regression analysis (P = .017, R² = 0.33). The 3-month combined exercise training program significantly improved several cardiometabolic parameters and reduced retinol binding protein-4 levels. Changes in glypican-4 levels after the exercise program were significantly different between subjects with an increased WHR compared with those with a decreased WHR (P = .034). CONCLUSION: A gender-based difference in circulating glypican-4 levels was apparent as these were increased in women with NAFLD and related to body fat distribution, insulin resistance, and arterial stiffness.

How safe and effective is routine left hand-assisted laparoscopic donor nephrectomy with multiple renal arteries? A high-volume, single-center experience.

BACKGROUND: We investigated the safety and effectiveness of routine harvest of the left kidney for renal transplantation regardless of the presence of multiple renal arteries to obtain the longer renal vein. PATIENTS AND METHODS: Between February 2000 and July 2008, 325 patients underwent left hand-assisted laparoscopic living donor nephrectomy. The true renal arterial anatomy as evaluated intraoperatively was compared with the renal arterial anatomy by computed tomography (CT). We compared the results for the patients with a single renal artery (group I) with the patients with multiple renal arteries (group II) in terms of the donor and recipient outcomes. RESULTS: Multiple renal arteries in left kidney were identified in 86 patients (26.5%). Thirty-seven CTs (11.4%) were in discord with the renal arterial anatomy evaluated intraoperatively. There was no difference in age, gender, body mass index, estimated blood loss, complication rate, or length of hospital stay between the 2 groups in the donor. Although the warm ischemic time and the operation time were significantly longer in group II (P = .008 and .001), overall graft survival was similar between the groups. CONCLUSION: Routine harvest of the left kidney can be performed safely and effectively for the donor and recipient, even in the presence of multiple renal arteries.