A Systematic Guideline by the ASPN Workgroup on the Evidence, Education, and Treatment Algorithm for Painful Diabetic Neuropathy: SWEET.

Introduction: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN. Objective: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process. Results: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria. Conclusion: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.

Neuromodulation for the management of chronic pelvic pain syndromes: A systematic review.

BACKGROUND: Chronic pelvic pain is a burdensome condition that involves multiple medical sub-specialties and is often difficult to treat. Sacral stimulation for functional bladder disease has been well established, but little large-scale evidence exists regarding utilization of other neuromodulation techniques to treat chronic pelvic pain. Emerging evidence does suggest that neuromodulation is a promising treatment, and we aim to characterize the use and efficacy of such techniques for treating chronic pelvic pain syndromes. MATERIALS AND METHODS: A systematic review of the literature demonstrating the treatment of chronic pelvic pain syndromes with neuromodulation. Abstracts were reviewed and selected for inclusion, including case series, prospective studies, and randomized controlled trials (RCTs). Case studies and publications in abstract only were not included. The reporting for this systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed using MEDLINE, Embase, Cochrane Library, PubMed, CINAHL, and Scopus. RESULTS: A total of 50 studies were included in this review, three of which were randomized controlled trials, and the remaining were prospective and retrospective case series. The range of pelvic pain conditions treated included interstitial cystitis, peripheral neuralgia, pudendal neuralgia, gastrointestinal pain, urogenital pain, sacroiliac joint pain, and visceral chronic pelvic pain. We reported on outcomes involving pain, functionality, psychosocial improvement, and medication reduction. CONCLUSIONS: Neuromodulation is a growing treatment for various chronic pain syndromes. Peripheral nerve stimulation was the least studied form of stimulation. Posterior tibial nerve stimulation appears to offer short-term benefit, but long-term results are challenging. Sacral nerve stimulation is established for use in functional bladder syndromes and appears to offer pain improvement in these patients as well. Dorsal root ganglion stimulation and spinal cord stimulation have been used for a variety of conditions with promising results. Further studies of homogeneous patient populations are necessary before strong recommendations can be made at this time, although pooled analysis may also be impactful.

Best Practice Guidelines on the Diagnosis and Treatment of Vertebrogenic Pain with Basivertebral Nerve Ablation from the American Society of Pain and Neuroscience.

Chronic low back pain is a worldwide leading cause of pain and disability. Degenerative disc disease has been the presumptive etiology in the majority of cases of chronic low back pain (CLBP). More recent study and treatments have discovered that the vertebral endplates play a large role in CLBP in a term defined as vertebrogenic back pain. As the vertebral endplates are highly innervated via the basivertebral nerve (BVN), this has resulted in a reliable target in treating patients suffering from vertebrogenic low back pain (VLBP). The application of BVN ablation for patients suffering from VLBP is still in its early stages of adoption and integration into spine care pathways. BVN ablation is grounded in a solid foundation of both pre-clinical and clinical evidence. With the emergence of this therapeutic option, the American Society of Pain and Neuroscience (ASPN) identified the need for formal evidence-based guidelines for the proper identification and selection of patients for BVN ablation in patients with VLBP. ASPN formed a multidisciplinary work group tasked to examine the available literature and form best practice guidelines on this subject. Based on the United States Preventative Task Force (USPSTF) criteria for grading evidence, gives BVN ablation Level A grade evidence with high certainty that the net benefit is substantial in appropriately selected individuals.

An overview of painful diabetic peripheral neuropathy: Diagnosis and treatment advancements.

Diabetes mellitus remains a public health problem, affecting 422 million people worldwide. Currently, there is no consensus around treating painful diabetic peripheral neuropathy in a step-wise manner. Among the non-pharmacological interventions, neuromodulation has become a promising alternative. Over the past decade, significant clinical trials have paved the way for prompt inclusion of high-frequency spinal cord stimulation within the painful diabetic peripheral neuropathy treatment algorithm. This article aims to provide an updated evidence-based approach for the management of painful diabetic peripheral neuropathy.

Peri-procedural Management of Implanted Spinal Cord Stimulators in Patients Undergoing Radiofrequency Ablation: A Case Report and Manufacturer-Specific Recommendations.

INTRODUCTION: Radiofrequency ablation (RFA) and spinal cord stimulation (SCS) are 2 common modalities used in management of various pain conditions. RFA generates heat and an electromagnetic field that can theoretically interfere with the functionality and longevity of the SCS device. This is problematic for patients who need RFA and have previously undergone implantation of an SCS device. CASE DESCRIPTION: We present a case highlighting the safe use of bipolar RFA in a patient who had previously undergone implantation of a cervical SCS device. DISCUSSION: We also present device-specific industry guidelines and recommendations for performing RFA in patients following SCS device implantation.

Use of the Satinsky clamp for hilar clamping during robotic partial nephrectomy: indications, technique, and multi-center outcomes.

A Satinsky clamp may be a backup option for hilar clamping during robotic partial nephrectomy (RPN) if there are challenges with application of bulldog clamps, but there are potential safety concerns. We evaluate outcomes of RPN using Satinsky vs. bulldog clamps, and provide tips for safe use of the Satinsky as a backup option. Using a multi-center database, we identified 1073 patients who underwent RPN between 2006 and 2013, and had information available about method of hilar clamping (bulldog clamp vs. Satinsky clamp). Patient baseline characteristics, tumor features, and perioperative outcomes were compared between the Satinsky and bulldog clamp groups. A Satinsky clamp was used for hilar clamping in 94 (8.8 %) RPN cases, and bulldog clamps were used in 979 (91.2 %) cases. The use of a Satinsky clamp was associated with greater operative time (198 vs. 175 min, p < 0.001), estimated blood loss (EBL, 200 vs. 100 ml, p < 0.001), warm ischemia time (WIT, 20 vs. 19 min, p = 0.036), transfusion rate (12.8 vs. 4.8 %, p = 0.001), and hospital stay (3 vs. 2 days, p < 0.001). Tumor characteristics and number of renal vessels were similar between groups. There were six intraoperative complications in the Satinsky clamp group, but none were directly related to the Satinsky clamp. On multivariable analysis, the use of the Satinsky clamp was not associated with increase in intraoperative or Clavien ≥3 postoperative complications, positive surgical margin rate or percentage change in estimated glomerular filtration rate. A Satinsky clamp can be a backup option for hilar clamping during challenging RPN cases, but requires careful technique, and was rarely necessary.

Multicentre outcomes of robot-assisted partial nephrectomy after major open abdominal surgery.

OBJECTIVE: To evaluate the outcomes of robot-assisted partial nephrectomy RAPN after major prior abdominal surgery (PAS) using a large multicentre database. PATIENTS AND METHODS: We identified 1 686 RAPN from five academic centres between 2006 and 2014. In all, 216 patients had previously undergone major PAS, defined as having an open upper midline/ipsilateral incision. Perioperative outcomes were compared with those 1 470 patients who had had no major PAS. The chi-squared test and Mann-Whitney U-test were used for categorical and continuous variables, respectively. RESULTS: There was no statistically significant difference in Charlson comorbidity index, tumour size, R.E.N.A.L. nephrometry score or preoperative estimated glomerular filtration rate (eGFR) between the groups. Age and body mass index were higher in patients with PAS. The PAS group had a higher estimated blood loss (EBL) but this did not lead to a higher transfusion rate. A retroperitoneal approach was used more often in patients with major PAS (11.2 vs 5.4%), although this group did not have a higher percentage of posterior tumours (38.8 vs 43.3%, P = 0.286). Operative time, warm ischaemia time, length of stay, positive surgical margin, percentage change in eGFR, and perioperative complications were not significantly different between the groups. CONCLUSIONS: RAPN in patients with major PAS is safe and feasible, with increased EBL but no increased rate of transfusion. Patients with major PAS had almost twice the likelihood of having a retroperitoneal approach.

Validation of the Caprini Venous Thromboembolism Risk Assessment Model in Critically Ill Surgical Patients.

IMPORTANCE: Appropriate risk stratification for venous thromboembolism (VTE) is essential to providing appropriate thromboprophylaxis and avoiding morbidity and mortality. OBJECTIVE: To validate the Caprini VTE risk assessment model in a previously unstudied high-risk cohort: critically ill surgical patients. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of 4844 adults (≥18 years old) admitted to a 20-bed surgical intensive care unit in a large tertiary care academic hospital during a 5-year period (July 1, 2007, through June 30, 2012). MAIN OUTCOMES AND MEASURES: The main study outcome was VTE (defined as patients with deep vein thrombosis or pulmonary embolism) that occurred during the patient's initial hospital admission. RESULTS: The study population was distributed among risk levels as follows: low, 5.3%; moderate, 19.9%; high, 31.6%; highest, 25.4%; and superhigh, 14.9%. The overall incidence of inpatient VTE was 7.5% and increased with risk level: 3.5% in low-risk patients, 5.5% in moderate-risk patients, 6.6% in high-risk patients, 8.6% in highest-risk patients, and 11.5% in superhigh-risk patients. Patients with Caprini scores greater than 8 were significantly more likely to develop inpatient VTE events when compared with patients with Caprini scores of 7 to 8 (odds ratio [OR], 1.37; 95% CI, 1.02-1.85; P = .04), 5 to 6 (OR, 1.35; 95% CI, 1.16-1.57; P < .001), 3 to 4 (OR, 1.30; 95% CI, 1.16-1.47; P < .001), or 0 to 2 (OR, 1.37; 95% CI, 1.16-1.64; P < .001). Similarly, patients with Caprini scores of 7 to 8 were significantly more likely to develop inpatient VTE when compared with patients with Caprini scores of 5 to 6 (OR, 1.33; 95% CI, 1.01-1.75; P = .04), 3 to 4 (OR, 1.27; 95% CI, 1.08-1.51; P = .005), or 0 to 2 (OR, 1.38; 95% CI, 1.10-1.74; P = .006). CONCLUSIONS AND RELEVANCE: The Caprini VTE risk assessment model is valid. This study supports the use of individual risk assessment in critically ill surgical patients.

We can rebuild it: reconstructive solutions for structural urologic diseases.

Bladder augmentation and urinary diversion have become standard of care as surgical treatments for structural and functional disorders affecting the bladder, both in children and adults. With improved medical care, long-term survival of these patients is expected. Common medical problems that can occur such as metabolic side effects including acid-base imbalances and nutritional issues need to be anticipated and addressed. In addition, surgical problems caused by impaired urinary drainage, namely stones and urinary tract infections, and mechanical factors related to catheterizable channels and continence also may compound postoperative management. The risk of malignancy after bladder augmentation and substitution, and appropriate surveillance for this, remains to be clearly defined.

Robotic partial nephrectomy for renal tumours in obese patients: Perioperative outcomes in a multi-institutional analysis.

INTRODUCTION: We sought to evaluate the association of obesity with surgical outcomes of robotic partial nephrectomy (RPN) using a large, multicentre database. METHODS: We identified 1836 patients who underwent RPN from five academic centres from 2006-2014. A total of 806 patients were obese (body mass index [BMI] ≥30 kg/m(2)). Patient characteristics and outcomes were compared between obese and non-obese patients. Multivariable analysis was used to assess the association of obesity on RPN outcomes. RESULTS: A total of 806 (44%) patients were obese with median BMI of 33.8kg/m(2). Compared to non-obese patients, obese patients had greater median tumour size (2.9 vs. 2.5cm, p<0.001), mean RENAL nephrometry score (7.3 vs. 7.1, p=0.04), median operating time (176 vs. 165 min, p=0.002), and median estimated blood loss (EBL, 150 vs. 100 ml, p=0.002), but no difference in complications. Obesity was not an independent predictor of operative time or EBL on regression analysis. Among obese patients, males had a greater EBL (150 vs. 100 ml, p<0.001), operative time (180 vs. 166 min, p<0.001) and warm ischemia time (WIT, 20 vs. 18, p=0.001), and male sex was an independent predictor of these outcomes on regression analysis. CONCLUSIONS: In this large, multicentre study on RPN, obesity was not associated with increased complications and was not an independent predictor of operating time or blood loss. However, in obese patients, male gender was an independent predictor of greater EBL, operative time, and WIT. Our results indicate that obesity alone should not preclude consideration for RPN.

Inadequate venous thromboembolism risk stratification predicts venous thromboembolic events in surgical intensive care unit patients.

BACKGROUND: Surgical intensive care unit (SICU) patients are known to be at high risk for venous thromboembolism (VTE). The 2005 Caprini Risk Assessment Model (RAM) predicts VTE risk in surgical patients. However, a physician's ability to accurately complete this RAM and the effect that inaccurate RAM completion might have on VTE risk remain unknown. STUDY DESIGN: Between 2009 and 2012, physicians completed a 2005 Caprini score for all SICU admissions at our institution. For comparison, we used a previously validated, computer-generated score. Regression-based techniques examined the effect of inadequate risk stratification on inpatient VTE risk, when controlling for other confounders. RESULTS: Among 3,338 consecutive SICU admissions, 55.2% had computer-generated scores that were higher than the physician-reported score, and 20.6% of scores were equal. Computer-generated scores were higher than physician-reported scores for both median (6 vs 5) and interquartile range (5 to 8 vs 3 to 7). Inter-rater reliability between the 2 scores was poor (kappa = 0.238). Risk score underestimation by ≥2 points was significantly associated with inpatient VTE (7.67% vs 4.59%, p = 0.002). Regression analysis demonstrated that each additional day's delay in chemoprophylaxis (odds ratio [OR] 1.05, 95% CI 1.01 to 1.08, p = 0.011) and under-risk stratification by ≥2 points (OR 2.46, 95% CI 1.53 to 3.96, p < 0.001) were independent predictors of inpatient VTE, as were higher admission APACHE score, personal history of VTE, recent pneumonia, and younger age. CONCLUSIONS: Physicians under-risk stratify SICU patients when using the 2005 Caprini RAM. As hospitals incorporate electronic medical records into daily practice, computer-calculated Caprini scores may result in more accurate VTE risk stratification. Inadequate VTE risk assessment and delay to chemoprophylaxis carry independent and significant increased risk for VTE.

Selective targeting of tumorigenic cancer cell lines by microtubule inhibitors.

For anticancer drug therapy, it is critical to kill those cells with highest tumorigenic potential, even when they comprise a relatively small fraction of the overall tumor cell population. We have used the established NCI/DTP 60 cell line growth inhibition assay as a platform for exploring the relationship between chemical structure and growth inhibition in both tumorigenic and non-tumorigenic cancer cell lines. Using experimental measurements of "take rate" in ectopic implants as a proxy for tumorigenic potential, we identified eight chemical agents that appear to strongly and selectively inhibit the growth of the most tumorigenic cell lines. Biochemical assay data and structure-activity relationships indicate that these compounds act by inhibiting tubulin polymerization. Yet, their activity against tumorigenic cell lines is more selective than that of the other microtubule inhibitors in clinical use. Biochemical differences in the tubulin subunits that make up microtubules, or differences in the function of microtubules in mitotic spindle assembly or cell division may be associated with the selectivity of these compounds.

Microparticle surface protein are associated with experimental venous thrombosis: a preliminary study.

Microparticles are small membrane vesicles released from activated cells and are associated with thrombosis and inflammation. Microparticle contain a unique subset of surface protein derived form the parent cell and may be responsible for their diverse biological functions. To identify these proteins, juvenile baboons (Papio anubis, n = 4) underwent iliac vein thrombosis with 6-hour balloon occlusion. Plasma samples were taken at baselines and at 2 days postthrombosis for microparticle analysis. Microparticles were extracted from platelet-poor plasma, digest separately with trypsin and tagged using isobaric tagging for relative and absolute quantitation reagents. The digests were subjected to 2-dimensional liquid chromatographic separation followed by matrix-assisted laser desorption/ionization tandem mass spectrometry. Peak lists were generated and searched against all primate sequences. For protein identity, a minimum of 2 peptides at 95% confidence interval was required. Later, isobaric tagging for relative and absolute quantitation ratios were generated comparing relative protein level of day 2 to baseline. The proteomic analysis was performed twice for each blood sample, totaling 8 experiments. Proteins were considered elevated of depressed if the isobaris tagging for relative and absolute quantitation ratio deviated by 20% changes from normal and a P value less than .05. Significantly, 7 proteins were differentially expressed on day 2 compared to baseline, and appeared in at least 3 animals and regulated in at least 4 experiment. Among these 7 proteins, upregulated proteins include various forms of fibrinogen and alpha-1-antichymotrypsin and downregulated proteins include immunoglobulins. These proteins influence thrombosis and inflammation through hemostatic plug formation (fibrinogen), inhibiting neutrophil adhesion (alpha-1-antichymoptrypsin), and immunoregulation (immunoglobulins). Further studies are needed to confirm the mechanistic role of these proteins in the pathogenesis of venous thrombosis.