Impact of Colic Pain as a Significant Factor for Predicting the Stone Free Rate of One-Session Shock Wave Lithotripsy for Treating Ureter Stones: A Bayesian Logistic Regression Model Analysis

Purpose

This study was conducted to evaluate colic pain as a prognostic pretreatment factor that can influence ureter stone clearance and to estimate the probability of stone-free status in shock wave lithotripsy (SWL) patients with a ureter stone.

Materials and Methods

We retrospectively reviewed the medical records of 1,418 patients who underwent their first SWL between 2005 and 2013. Among these patients, 551 had a ureter stone measuring 4–20 mm and were thus eligible for our analyses. The colic pain as the chief complaint was defined as either subjective flank pain during history taking and physical examination. Propensity-scores for established for colic pain was calculated for each patient using multivariate logistic regression based upon the following covariates: age, maximal stone length (MSL), and mean stone density (MSD). Each factor was evaluated as predictor for stone-free status by Bayesian and non-Bayesian logistic regression model.

Results

After propensity-score matching, 217 patients were extracted in each group from the total patient cohort. There were no statistical differences in variables used in propensity- score matching. One-session success and stone-free rate were also higher in the painful group (73.7% and 71.0%, respectively) than in the painless group (63.6% and 60.4%, respectively). In multivariate non-Bayesian and Bayesian logistic regression models, a painful stone, shorter MSL, and lower MSD were significant factors for one-session stone-free status in patients who underwent SWL.

Conclusions

Colic pain in patients with ureter calculi was one of the significant predicting factors including MSL and MSD for one-session stone-free status of SWL.     

Extracorporeal Shock Wave Lithotripsy for Management of Residual Stones after Ureterolithotripsy versus Mini-Percutaneous Nephrolithotomy: A Retrospective Study

Purpose

To compare the efficacy of extracorporeal shock wave lithotripsy in managing residual stones after ureterolithotripsy and mini-percutaneous nephrolithotomy.

Materials and Methods

A retrospective study was carried out of 71 patients with proximal urinary tract stones (greater than 10 mm) who underwent ureterolithotripsy or mini-percutaneous nephrolithotomy at a single institution from 2009 to 2011. The 71 patients were divided into two groups: group I (n = 37) comprised patients who underwent ureterolithotripsy, and group II (n = 34) comprised patients who underwent mini-percutaneous nephrolithotomy. Clinical characteristics, stone-free rates, stone demographics, and complications were evaluated.

Results

The overall stone-free rate was 90.1%. The stone-free rates in groups I and II were 97.3% and 82.4%, respectively. There was a statistically significant difference in the stone-free rates between groups I and II (P = 0.035). Neither serious intraoperative nor postoperative complications were observed. No significant difference in complications was observed between the two groups (P = 0.472).

Conclusions

The results of our study suggest that extracorporeal shock wave lithotripsy is an effective and safe auxiliary procedure for managing residual stones after primary endoscopic surgery. This procedure is associated with a satisfactory stone-free rate and a low complication rate, particularly for residual stones after ureteroscopic procedures.     

Cardiac Troponin Is a Predictor of Septic Shock Mortality in Cancer Patients in an Emergency Department: A Retrospective Cohort Study

BackgroundSeptic shock may be associated with myocardial damage; however, the prognostic value of cardiac enzymes in cancer patients with septic shock is unknown. In this study, we evaluated the prognostic significance of cardiac enzymes in combination with established prognostic factors in predicting the 7-day mortality rate of patients with septic shock, and we constructed a new scoring system, Septic Oncologic Patients in Emergency Department (SOPED), which includes cardiac enzymes, to predict 7-day mortality rates.ConclusionsTroponin-I >0.05 ng/mL was an important predictor of short-term mortality (≤7 days). The SOPED scoring system, which incorporated troponin-I, was more prognostically accurate than were other scores for 7-day mortality. Large multicenter studies are needed to verify our results and prospectively validate the prognostic performance of the SOPED score.     

Preoperative Neutrophil-to-Lymphocyte Ratio Is a Predictor of Recurrence following Thermal Ablation for Recurrent Hepatocellular Carcinoma: A Retrospective Analysis

Purpose

The aim of this study is to determine the predictive value of preoperative blood neutrophil-to-lymphocyte ratio (NLR) for recurrence in recurrent hepatocellular carcinoma (RHCC) patients following thermal ablation.

Material and Methods

This retrospective study enrolled 506 RHCC patients who underwent thermal ablation from April 2006 to April 2014. The clinicopathological parameters including NLR were evaluated to identify predictors of recurrence rate after thermal ablation. A Cox multiple regression analysis was performed to determine the parameters that predicted recurrence in RHCC patients. The best cutoff value of NLR was determined with time-dependent receiver operating characteristic (ROC) curve analysis. The recurrence-free survival (RFS) rate was determined in patients with high and low NLR.

Results

The multivariate Cox proportional hazard model analysis showed that NLR was a prognostic factor in recurrence-free survival. NLR ≥2.14 was evaluated (AUROC = 0.824; P<0.001), and 183 of 506 patients (36.2%) had a NLR of more than 2.14. During the follow-up period (12–96 months), the 1-, and 3- year recurrence rates were 20.7% and 31.6% in low NLR group, respectively. These recurrence rates were significantly less than those in the high NLR group (57.9% and 82.5%, respectively) (P<0.001). A recurrence-free survival analyses demonstrated that the RFS in the low NLR group (67.2%) was significantly higher than that in the high NLR group (13.1%) (P<0.001).

Conclusion

Our results show that preoperative NLR is a predictor for re-recurrence after thermal ablation in RHCC patients. Additionally, patients with NLR <2.14 have a lower recurrence rate, which may improve the clinical management of RHCC patients.     

Occupancy Models for Monitoring Marine Fish: A Bayesian Hierarchical Approach to Model Imperfect Detection with a Novel Gear Combination

Occupancy models using incidence data collected repeatedly at sites across the range of a population are increasingly employed to infer patterns and processes influencing population distribution and dynamics. While such work is common in terrestrial systems, fewer examples exist in marine applications. This disparity likely exists because the replicate samples required by these models to account for imperfect detection are often impractical to obtain when surveying aquatic organisms, particularly fishes. We employ simultaneous sampling using fish traps and novel underwater camera observations to generate the requisite replicate samples for occupancy models of red snapper, a reef fish species. Since the replicate samples are collected simultaneously by multiple sampling devices, many typical problems encountered when obtaining replicate observations are avoided. Our results suggest that augmenting traditional fish trap sampling with camera observations not only doubled the probability of detecting red snapper in reef habitats off the Southeast coast of the United States, but supplied the necessary observations to infer factors influencing population distribution and abundance while accounting for imperfect detection. We found that detection probabilities tended to be higher for camera traps than traditional fish traps. Furthermore, camera trap detections were influenced by the current direction and turbidity of the water, indicating that collecting data on these variables is important for future monitoring. These models indicate that the distribution and abundance of this species is more heavily influenced by latitude and depth than by micro-scale reef characteristics lending credence to previous characterizations of red snapper as a reef habitat generalist. This study demonstrates the utility of simultaneous sampling devices, including camera traps, in aquatic environments to inform occupancy models and account for imperfect detection when describing factors influencing fish population distribution and dynamics.     

A Bayesian Approach for Modeling Cattle Movements in the United States: Scaling up a Partially Observed Network

Networks are rarely completely observed and prediction of unobserved edges is an important problem, especially in disease spread modeling where networks are used to represent the pattern of contacts. We focus on a partially observed cattle movement network in the U.S. and present a method for scaling up to a full network based on Bayesian inference, with the aim of informing epidemic disease spread models in the United States. The observed network is a 10% state stratified sample of Interstate Certificates of Veterinary Inspection that are required for interstate movement; describing approximately 20,000 movements from 47 of the contiguous states, with origins and destinations aggregated at the county level. We address how to scale up the 10% sample and predict unobserved intrastate movements based on observed movement distances. Edge prediction based on a distance kernel is not straightforward because the probability of movement does not always decline monotonically with distance due to underlying industry infrastructure. Hence, we propose a spatially explicit model where the probability of movement depends on distance, number of premises per county and historical imports of animals. Our model performs well in recapturing overall metrics of the observed network at the node level (U.S. counties), including degree centrality and betweenness; and performs better compared to randomized networks. Kernel generated movement networks also recapture observed global network metrics, including network size, transitivity, reciprocity, and assortativity better than randomized networks. In addition, predicted movements are similar to observed when aggregated at the state level (a broader geographic level relevant for policy) and are concentrated around states where key infrastructures, such as feedlots, are common. We conclude that the method generally performs well in predicting both coarse geographical patterns and network structure and is a promising method to generate full networks that incorporate the uncertainty of sampled and unobserved contacts.     

Artificial Cervical Vertebra and Intervertebral Complex Replacement through the Anterior Approach in Animal Model: A Biomechanical and In Vivo Evaluation of a Successful Goat Model

This was an in vitro and in vivo study to develop a novel artificial cervical vertebra and intervertebral complex (ACVC) joint in a goat model to provide a new method for treating degenerative disc disease in the cervical spine. The objectives of this study were to test the safety, validity, and effectiveness of ACVC by goat model and to provide preclinical data for a clinical trial in humans in future. We designed the ACVC based on the radiological and anatomical data on goat and human cervical spines, established an animal model by implanting the ACVC into goat cervical spines in vitro prior to in vivo implantation through the anterior approach, and evaluated clinical, radiological, biomechanical parameters after implantation. The X-ray radiological data revealed similarities between goat and human intervertebral angles at the levels of C2-3, C3-4, and C4-5, and between goat and human lordosis angles at the levels of C3-4 and C4-5. In the in vivo implantation, the goats successfully endured the entire experimental procedure and recovered well after the surgery. The radiological results showed that there was no dislocation of the ACVC and that the ACVC successfully restored the intervertebral disc height after the surgery. The biomechanical data showed that there was no significant difference in range of motion (ROM) or neural zone (NZ) between the control group and the ACVC group in flexion-extension and lateral bending before or after the fatigue test. The ROM and NZ of the ACVC group were greater than those of the control group for rotation. In conclusion, the goat provides an excellent animal model for the biomechanical study of the cervical spine. The ACVC is able to provide instant stability after surgery and to preserve normal motion in the cervical spine.     

Impact on Clinical and Cost Outcomes of a Centralized Approach to Acute Stroke Care in London: A Comparative Effectiveness Before and After Model

Background

In July 2010 a new multiple hub-and-spoke model for acute stroke care was implemented across the whole of London, UK, with continuous specialist care during the first 72 hours provided at 8 hyper-acute stroke units (HASUs) compared to the previous model of 30 local hospitals receiving acute stroke patients. We investigated differences in clinical outcomes and costs between the new and old models.

Methods

We compared outcomes and costs ‘before’ (July 2007–July 2008) vs. ‘after’ (July 2010–June 2011) the introduction of the new model, adjusted for patient characteristics and national time trends in mortality and length of stay. We constructed 90-day and 10-year decision analytic models using data from population based stroke registers, audits and published sources. Mortality and length of stay were modelled using survival analysis.

Findings

In a pooled sample of 307 patients ‘before’ and 3156 patients ‘after’, survival improved in the ‘after’ period (age adjusted hazard ratio 0.54; 95% CI 0.41–0.72). The predicted survival rates at 90 days in the deterministic model adjusted for national trends were 87.2% ‘before’ % (95% CI 86.7%–87.7%) and 88.7% ‘after’ (95% CI 88.6%–88.8%); a relative reduction in deaths of 12% (95% CI 8%–16%). Based on a cohort of 6,438 stroke patients, the model produces a total cost saving of £5.2 million per year at 90 days (95% CI £4.9-£5.5 million; £811 per patient).

Conclusion

A centralized model for acute stroke care across an entire metropolitan city appears to have reduced mortality for a reduced cost per patient, predominately as a result of reduced hospital length of stay.     

Bilateral Nerve Alterations in a Unilateral Experimental Neurotrophic Keratopathy Model: A Lateral Conjunctival Approach for Trigeminal Axotomy

To study bilateral nerve changes in a newly developed novel mouse model for neurotrophic keratopathy by approaching the trigeminal nerve from the lateral fornix. Surgical axotomy of the ciliary nerve of the trigeminal nerve was performed in adult BALB/c mice at the posterior sclera. Axotomized, contralateral, and sham-treated corneas were excised on post-operative days 1, 3, 5, 7 and 14 and immunofluorescence histochemistry was performed with anti-β-tubulin antibody to evaluate corneal nerve density. Blink reflex was evaluated using a nylon thread. The survival rate was 100% with minimal bleeding during axotomy and a surgical time of 8±0.5 minutes. The blink reflex was diminished at day 1 after axotomy, but remained intact in the contralateral eyes in all mice. The central and peripheral subbasal nerves were not detectable in the axotomized cornea at day 1 (p<0.001), compared to normal eyes (101.3±14.8 and 69.7±12.0 mm/mm² centrally and peripherally). Interestingly, the subbasal nerve density in the contralateral non-surgical eyes also decreased significantly to 62.4±2.8 mm/mm² in the center from day 1 (p<0.001), but did not change in the periphery (77.3±11.7 mm/mm², P = 0.819). Our novel trigeminal axotomy mouse model is highly effective, less invasive, rapid, and has a high survival rate, demonstrating immediate loss of subbasal nerves in axotomized eyes and decreased subbasal nerves in contralateral eyes after unilateral axotomy. This model will allow investigating the effects of corneal nerve damage and serves as a new model for neurotrophic keratopathy.     

Successful treatment for perinephric abscess with recombinant human granulocyte colony-stimulating factor following nephrectomy in a patient of myelodysplastic syndrome: A case report

The 35-year-old man with myelodysplastic syndrome (MDS) and granulocytopenia with dry cough and high fever was eventually found to have a left perinephric abscess ofStaphylococcus aureus. He underwent left nephrectomy and drainage of perinephric space in conjunction with appropriate antibiotics. However, because of persistent granulocytopenia,Staph. aureus never cleared up with formation of only poor granulation. Recombinant human granulocyte colony-stimulating factor (G-CSF) was added to the above treatment leading to prompt improvement in granulocytopenia and emergence of the good granulation tissue. G-CSF will probably become one of the important agents in treating MDS with granulocytopenia.     

Dickkopf-1 as a Novel Predictor Is Associated with Risk Stratification by GRACE Risk Scores for Predictive Value in Patients with Acute Coronary Syndrome: A Retrospective Research

Objective

Dickkopf-1 (DKK-1), a major regulator of the Wnt pathway, plays an important role in cardiovascular disease. However, no study has evaluated the association of DKK-1 and acute coronary syndrome (ACS). We investigated this association and whether the Global Registry of Acute Coronary Events (GRACE) hospital-discharge risk score predicting major adverse cardiac events (MACE) can be improved by adding the DKK-1 value.

Methods

We enrolled 291 patients (46 with ST-segment elevation myocardial infarction [STEMI] and 245 with non-ST elevated ACS [NSTE-ACS]) who were divided into groups by tertiles of baseline plasma DKK-1 level measured by ELISA. The GRACE risk score was calculated and predictive value alone and together with DKK-1 and/or high-sensitivity C-reactive protein (hs-CRP) level were assessed, respectively.

Results

Compared with patients with NSTE-ACS, those with STEMI had higher plasma DKK-1 level at baseline (P = 0.006). Plasma DKK-1 level was correlated with hs-CRP level (r = 0.295, P<0.001) and was greater with high than intermediate or low GRACE scores (P = 0.002 and P<0.001, respectively). We found 44 (15.1%) MACEs during a median 2-year follow-up. DKK-1 levels were higher for patients with than without events (P<0.001). The rate of MACE increased with increasing DKK-1 level (P<0.001). The area under the receiver operating characteristic curve for GRACE score with MACE was 0.524 and improved to 0.791 with the addition of hs-CRP level, 0.775 with the addition of DKK-1 level and 0.847 with both values added.

Conclusions

DKK-1 is an independent predictor of long-term MACE of patients with ACS. The long-term predictive ability of post-discharge GRACE score may be enhanced by adding DKK-1 level.     

A Loop-Mediated Isothermal Amplification (LAMP) Assay for Early Detection of Schistosoma mansoni in Stool Samples: A Diagnostic Approach in a Murine Model

Background

Human schistosomiasis, mainly due to Schistosoma mansoni species, is one of the most prevalent parasitic diseases worldwide. To overcome the drawbacks of classical parasitological and serological methods in detecting S. mansoni infections, especially in acute stage of the disease, development of cost-effective, simple and rapid molecular methods is still needed for the diagnosis of schistosomiasis. A promising approach is the loop-mediated isothermal amplification (LAMP) technology. Compared to PCR-based assays, LAMP has the advantages of reaction simplicity, rapidity, specificity, cost-effectiveness and higher amplification efficiency. Additionally, as results can be inspected by the naked eye, the technique has great potential for use in low-income countries.

Methodology/Principal findings

A sequence corresponding to a mitochondrial S. mansoni minisatellite DNA region was selected as a target for designing a LAMP-based method to detect S. mansoni DNA in stool samples. We used a S. mansoni murine model to obtain well defined stool and sera samples from infected mice with S. mansoni cercariae. Samples were taken weekly from week 0 to 8 post-infection and the Kato-Katz and ELISA techniques were used for monitoring the infection. Primer set designed were tested using a commercial reaction mixture for LAMP assay and an in house mixture to compare results. Specificity of LAMP was tested using 16 DNA samples from different parasites, including several Schistosoma species, and no cross-reactions were found. The detection limit of our LAMP assay (SmMIT-LAMP) was 1 fg of S. mansoni DNA. When testing stool samples from infected mice the SmMIT-LAMP detected S. mansoni DNA as soon as 1 week post-infection.

Conclusions/Significance

We have developed, for the first time, a cost-effective, easy to perform, specific and sensitive LAMP assay for early detection of S. mansoni in stool samples. The method is potentially and readily adaptable for field diagnosis and disease surveillance in schistosomiasis-endemic areas.     

IMD-0354 Targets Breast Cancer Stem Cells: A Novel Approach for an Adjuvant to Chemotherapy to Prevent Multidrug Resistance in a Murine Model

Although early detection of breast cancer improved in recent years, prognosis of patients with late stage breast cancer remains poor, mostly due to development of multidrug resistance (MDR) followed by tumor recurrence. Cancer stem cells (CSCs), with higher drug efflux capability and other stem cell-like properties, are concentrated in a side population (SP) of cells, which were proposed to be responsible for MDR and tumor repopulation that cause patients to succumb to breast cancer. Therefore, targeting of CSCs as an adjuvant to chemotherapy should be able to provide a more effective treatment of this disease. Here, we used IMD-0354, an inhibitor of NF-κB, identified for targeting CSCs, in a combination therapy with doxorubicin encapsulated in targeted nanoparticles. IMD-0354 did target CSCs, evidenced by a decrease in the SP, demonstrated by the inhibition of the following: dye/drug efflux, reduction in ABC transporters as well as in colony formation in soft agar and low attachment plates. Decrease of stem-like gene expression of Oct4, Nanog and Sox2, and apoptosis resistance related to the Survivin gene also was observed after treatment with this compound. In addition, IMD-0354 targeted non-CSCs as indicated by reducing viability and increasing apoptosis. Targeted drug delivery, achieved with a legumain inhibitor, proved to enhance drug delivery under hypoxia, a hallmark of the tumor microenvironment, but not under normoxia. Together, this allowed a safe, non-toxic delivery of both anticancer agents to the tumor microenvironment of mice bearing syngeneic metastatic breast cancer. Targeting both bulk tumor cells with a chemotherapeutic agent and CSCs with IMD-0354 should be able to reduce MDR. This could eventually result in decreasing tumor recurrences and/or improve the outcome of metastatic disease.