Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial.

BACKGROUND: People with type 2 diabetes and albuminuria are at an elevated risk for cardiac and renal events. The optimal biomarkers to aid disease prediction and to understand the benefits of sodium-glucose cotransporter-2 inhibition remain unclear. METHODS: Among 2627 study participants in the CREDENCE trial (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, growth differentiation factor-15, and IGFBP7 (insulin-like growth factor binding protein 7) were measured. The effect of canagliflozin on biomarker concentrations was evaluated. The prognostic potential of each biomarker on the primary outcome (a composite of end-stage kidney disease [dialysis, transplantation, or a sustained estimated glomerular filtration rate of <15 mL·min-1·1.73 m-2], doubling of the serum creatinine level, or renal death or cardiovascular death) was assessed. RESULTS: The median (quartiles 1 and 3) concentration of each biomarker was generally elevated: NT-proBNP, 180 ng/L (82, 442 ng/L); high-sensitivity cardiac troponin T, 19 ng/L (12, 29 ng/L); growth differentiation factor-15, 2595 ng/L (1852, 3775 ng/L); and IGFBP7, 121.8 ng/mL (105.4, 141.5 ng/mL). At 1 year, the biomarkers all rose by 6% to 29% in the placebo arm but only by 3% to 10% in the canagliflozin arm (all P<0.01 in multivariable linear mixed-effect models). Baseline concentrations of each biomarker were strongly predictive of cardiac and renal outcomes. When the biomarkers were analyzed together in a multimarker panel, individuals with high risk scores (hazard ratio [HR], 4.01 [95% CI, 2.52-6.35]) and moderate risk scores (HR, 2.39 [95% CI, 1.48-3.87]) showed a higher risk for the primary outcome compared with those with low risk scores. By 1 year, a 50% increase in NT-proBNP (HR, 1.11 [95% CI, 1.08-1.15]), high-sensitivity cardiac troponin T (HR, 1.86 [95% CI, 1.64-2.10]), growth differentiation factor-15 (HR, 1.45 [95% CI, 1.24-1.70]), and IGFBP7 (HR, 3.76 [95% CI, 2.54-5.56]) was associated with risk of the primary outcome. CONCLUSIONS: Multiple cardiorenal stress biomarkers are strongly prognostic in people with type 2 diabetes and albuminuria. Canagliflozin modestly reduced the longitudinal trajectory of rise in each biomarker. Change in the biomarker level in addition to the baseline level augments the primary outcome prediction. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02065791.

Comparing Robotic, Thoracoscopic, and Open Segmentectomy: A National Cancer Database Analysis.

INTRODUCTION: Minimally invasive approaches to lung resection have become widely acceptable and more recently, segmentectomy has demonstrated equivalent oncologic outcomes when compared to lobectomy for early-stage non-small cell lung cancer (NSCLC). However, studies comparing outcomes following segmentectomy by different surgical approaches are lacking. Our objective was to investigate the outcomes of patients undergoing robotic, video-assisted thoracoscopic surgery (VATS), or open segmentectomy for NSCLC using the National Cancer Database. METHODS: NSCLC patients with clinical stage I who underwent segmentectomy from 2010 to 2016 were identified. After propensity-score matching (1:4:1), multivariate logistic regression analyses were performed to determine predictors of 30-d readmissions, 90-d mortality, and overall survival. RESULTS: 22,792 patients met study inclusion. After matching, approaches included robotic (n = 2493; 17%), VATS (n = 9972; 66%), and open (n = 2493; 17%). An open approach was associated with higher 30-d readmissions (7% open versus 5.5% VATS versus 5.6% robot, P = 0.033) and 90-d mortality (4.4% open versus 2.2% VATS versus 2.5% robot, P < 0.001). A robotic approach was associated with improved 5-y survival (50% open versus 58% VATS versus 63% robot, P < 0.001). CONCLUSIONS: For patients with clinical stage I NSCLC undergoing segmentectomy, compared to the open approach, a VATS approach was associated with lower 30-d readmission and 90-d mortality. A robotic approach was associated with improved 5-y survival compared to open and VATS approaches when matched. Additional studies are necessary to determine if unrecognized covariates contribute to these differences.

Positive Bacterial Cultures on Spinal Wound Closure Do Not Predict Postoperative Outcomes.

BACKGROUND: Complex surgical back wounds represent significant morbidity in patients who have undergone spinal procedures requiring closure or revision by plastic surgeons. This study aimed to assess the utility of bacterial wound culture data for predicting surgical outcomes of wound management. METHODS: This study is a single-institution retrospective review of consecutive patients who required plastic surgery intervention for wound infection following spinal procedures between the years 2010 and 2021 (n = 70). Statistical analysis was performed for demographics, comorbidities, perioperative laboratory studies, and treatment methods. The primary outcomes of interest were rate of postoperative complications after soft tissue reconstruction and reconstructive failure. The secondary outcome of interest was time to healing in number of days. RESULTS: The overall complication rate after wound closure was 31.4%, with wound infection in 12.9%, seroma in 10%, dehiscence in 12.9%, and hematoma in 1.4%. Increasing number of debridements before wound closure increased the likelihood of a surgical complication of any kind (odds ratio [OR], 1.772; 95% confidence interval [CI], 1.045-3.002). Positive wound cultures before reconstruction were associated with development of seroma only (OR, 0.265; 95% CI, 0.078-0.893). Use of incisional vacuum-assisted closure devices significantly decreased the odds of postoperative wound dehiscence (OR, 0.179; 95% CI, 0.034-0.904) and increased odds of healing (hazard ratio, 3.638; 95% CI, 1.547-8.613). CONCLUSIONS: Positive wound cultures were not significantly associated with negative outcomes after complex closure or reconstruction of infected spinal surgical wounds. This finding emphasizes the importance of clinical judgment with a multidisciplinary approach to complex surgical back wounds over culture data for wound closure timing.

Outcomes in Patients with Heel Ulcerations that Underwent Below the Knee Amputations versus Vertical Contour Calcanectomy: Importance of Selection Criteria.

The aim of the study was to compare preoperative factors and postoperative outcomes in patients with heel ulcerations that primarily had a transtibial (below the knee) amputation (N=38) versus vertical contour calcanectomy (n=62). The groups had no statistical difference between their Charlson Comorbidity Index Score, a prognostic score of ten-year survival in patients with multiple comorbidities. The odds of primary closure was 21.1 times higher in patients that underwent below knee amputation compared to patients that underwent vertical contour calcanectomy [OR 21.1 (95% CI 3.89-114.21)]. The odds of positive soft tissue culture at time of closure were 17.1 times higher for patients that underwent vertical contour calcanectomy [OR 17.1 (95% CI 5.40-54.16)]. The odds of a patent posterior tibial artery was 3.3 times higher for patients that underwent vertical contour calcanectomy [OR 3.3 (95% 1.09-10.09)]. The secondary aim of the study was to evaluate preoperative factors and postoperative outcomes in patients with failed vertical contour calcanectomy, defined as needing a below knee amputation. The odds of vertical contour calcanectomy failure was 13.7 times higher in male patients [OR 13.7 (95% CI 1.80-107.60)]. Vertical contour calcanectomy failure was 5.7 times higher in patients with renal disease [OR 5.7 (95% CI 1.10-30.30)], and vertical contour calcanectomy failure was 16.1 times higher for patients who needed additional surgery post closure [OR 16.1 (95% CI 1.40-183.20)].

Presence of a patent pedal arch is the primary predictor of transmetatarsal amputation healing and limb salvage.

OBJECTIVE: Transmetatarsal amputation (TMA) is a durable and important functional limb salvage option. We have presented our results in identifying the angiographic predictors of TMA healing using single-institution retrospective data. METHODS: Consecutive patients within our institution who had undergone TMA and lower extremity arteriography from 2012 to 2020 were included. Patients whose TMA had healed were compared with those whose TMA had not healed. Using pre- and perioperative patient factors, in addition to the Global Limb Anatomic Staging System (GLASS) and evaluation of the tibial runoff vessels, multivariate analysis was used to define the predictors of TMA healing at 30 days and 1 year. For those patients who had undergone an intervention after TMA, including repeat interventions, the postintervention GLASS stage was calculated. All patients were followed up by the vascular surgeon using standard ultrasound surveillance and clinical examinations. Once the predictors had been identified, an analysis was performed to correlate the 30-day and 1-year limb salvage rates. RESULTS: A total of 89 patients had met the inclusion criteria for the study period. No difference was found in the GLASS femoropopliteal or infrapopliteal stages for those with a healed TMA and those without. After multivariate regression analysis, the presence of a patent pedal arch vs a nonintact arch had a 5.5 greater odds of TMA healing at 30 days but not at 1 year. Additionally, the presence of a patent arch was strongly associated with limb salvage at both 30 days (86% vs 49%; P < .01) and 1 year (79% vs 49%; P < .01). CONCLUSIONS: In the present series of patients who had undergone TMA and arteriography, with appropriate GLASS staging, we found patency of the pedal arch was a significant predictor of healing and limb salvage. The GLASS femoropopliteal and infrapopliteal stages did not predict for TMA healing.

A prospective pilot study to assess for histologic changes on vulvar biopsies in postmenopausal women with lichen sclerosus treated with fractionated CO2 laser therapy.

OBJECTIVES: To investigate the histologic characteristics of vulvar tissues before and after completion of fractionated carbon dioxide (CO2 ) laser therapy (FxCO2) for vulvar lichen sclerosus (LS). The secondary objective was to assess subjective improvement in symptoms via the Skindex-16 questionnaire. METHODS: This prospective single-arm study was conducted from April 2021 to August 2022 at one academic medical center. Ten postmenopausal women with biopsy-proven LS planning FxCO2 laser treatment were enrolled. Exclusion criteria included prior transvaginal mesh for prolapse, topical corticosteroid use within 8 weeks, prior pelvic radiation, malignancy, active genital infection, or pregnancy. The vulvovaginal SmartXide2-V2-LR laser system fractionated CO2 laser (DEKA) was utilized to treat visually affected areas of vulvar and perianal LS with a single pass. Subjects underwent three treatments 4-6 weeks apart. Subjects completed the Skindex-16 questionnaire and had vulvar biopsy at baseline and at 4 weeks after completion of fractionated CO2 laser therapy. Blinded histologic slides were scored by one dermatopathologist (Michael A. Cardis) rating from 1 to 5 the degree of dermal sclerosis, inflammation, and epidermal atrophy. Change scores were calculated as the difference between pre- and post-treatment scores for each subject. RESULTS: The 10 subjects enrolled had a mean age of 61 and most were white, privately insured, and had a college/graduate-level education. Post-fractionated CO2 laser treatment vulvar biopsies showed significant improvement in sclerosis and epidermal atrophy compared with pretreatment baseline biopsy specimens (p < 0.05) with no statistically significant change found in inflammation score. Skindex-16 and FSFI scores showed a trend towards improvement (p > 0.05 for both). A statistically significant correlation was found between change in sclerosis and Skindex-16 symptoms scores with an average change of 21.4 units in Skindex-16 symptoms score for every one-point change in histologic sclerosis score (p = 0.03). CONCLUSIONS: In postmenopausal women with vulvar LS undergoing fractionated CO2 laser, symptomatic improvements correlated with histologic change in degree of sclerosis on vulvar biopsy. These results demonstrate FxCO2 laser therapy as a promising option for the treatment of LS and suggest that further studies should assess degree of sclerosis on histopathology.

Treatment of refractory overactive bladder with OnabotulinumtoxinA vs PTNS: TROOP trial.

INTRODUCTION AND HYPOTHESIS: We hypothesized that patients with refractory overactive bladder (rOAB) have similar improvement with percutaneous tibial nerve stimulation (PTNS) and OnabotulinumtoxinA (BTX). METHODS: This multicenter cohort study compared BTX and PTNS in women with rOAB. Baseline information included Overactive Bladder Questionnaire (OABq) short form, Urinary Distress Inventory-6 (UDI-6), and voiding diary. Primary outcome was cure, defined as "very much better" or "much better" on the Patient Global Impression of Improvement (PGII) AND a reduction in OABq symptom severity scale (SSS) ≥10 at 3 months after treatment. Assuming 80% power to detect a ten-point difference in OABq-SSS, 80 participants were required per group. RESULTS: A total of 150 patients were enrolled; 97 completed 3 months of therapy and were included. At baseline, BTX patients had more detrusor overactivity (70% vs 40%, p = 0.025), urgency incontinence (UUI; OABq-SSS#6 4 vs 3, p = 0.02, SSS 65 vs 56, p = 0.04), but similar health-related quality of life (HRQL 49 vs 54, p = 0.28), voids (7 vs 8, p = 0.13), and UUI episodes (2 vs 2, p = 1.0). At 3 months, cure rates were similar: BTX 50% vs PTNS 44.2% (p = 0.56). Both groups had improved SSS (-37 vs -29, p = 0.08) and HRQL (31 vs 24, p = 0.14). Patients receiving BTX had a greater improvement in urgency (ΔOABq-SSS#2-3 vs -2; p = 0.02) and UUI (ΔOABq-SSS#6-2 vs -1; p = 0.02). No characteristics were predictive of cure. CONCLUSIONS: BTX resulted in significantly greater improvement in urgency and UUI than PTNS, but no difference in success based on PGII and OABq-SSS, which may be due to a lack of power.

Bacitracin for Injection Recall: Impact on Immediate Breast Implant Surgical Outcomes.

Background: Triple-antibiotic irrigation of breast implant pockets is a mainstay of infection prophylaxis in breast reconstruction and augmentation. The recall of bacitracin for injection due to risk of anaphylaxis and nephrotoxicity in January 2020, a staple component of the irrigation solution, has raised concern for worsened postoperative sequelae. This study aimed to investigate pre- and post-recall implant-based breast surgery to analyze the impact of bacitracin in irrigation solutions on infection rates. Methods: All implant-based breast reconstruction or augmentation surgeries from January 2019 to February 2021 were retrospectively reviewed. In a regression discontinuity study design, patients were divided into pre- and post-recall groups. Patient demographics, surgical details, and outcomes including infection rates were collected. Differences in complication rates were compared between groups and with surgical and patient factors. Results: 254 implants in 143 patients met inclusion criteria for this study, with 172 implants placed before recall and 82 placed after recall. Patients in each cohort did not differ in age, BMI, smoking status, or history of breast radiation or capsular contracture (p > 0.05). All breast pockets were irrigated with antibiotic solution, most commonly bacitracin, cefazolin, gentamycin, and povidone-iodine before recall (116,67.4%) and cefazolin, gentamycin, and povidone-iodine after recall (59,72.0%). There was no difference in incidence of infection (6.4% vs. 8.5%, p=0.551) or cellulitis (3.5% vs. 3.7%, p=0.959) before and after recall. Implant infection was associated with smoking history (p < 0.001) and increased surgical time (p=0.003). Conclusions: Despite the recent recall of bacitracin from inclusion in breast pocket irrigation solutions, our study demonstrated no detrimental impact on immediate complication rates. This shift in irrigation protocols calls for additional investigations into optimizing antibiotic combinations in solution, as bacitracin is no longer a viable option, to improve surgical outcomes and long-term benefits.

Popliteal artery patency is an indicator of ambulation and healing after below-knee amputation in vasculopaths.

BACKGROUND: The posterior flap is a conventional technique for closing a below-knee amputation (BKA) that uses the gastrocnemius and soleus muscle and relies on the popliteal and posterior compartment arteries. If the prior mentioned arterial blood supply is compromised, this flap likely relies on collateral flow. The purpose of this study is to identify and differentiate any significant associations between preoperative popliteal and tibial arterial flow and BKA outcomes and patient-reported function. METHODS: A retrospective review identified patients from a single tertiary wound care center who received BKAs and angiogram between 2010 and 2017 by a single surgeon. BKA complications, wound healing, and amputee ambulatory status at latest follow-up were all stratified for differences according to baseline tibial vessel run-off (VRO) status, popliteal artery patency, and popliteal angioplasty outcome. Chi-square, Fisher's exact, and Wilcoxon rank sum tests were used with significance defined as p ≤ 0.05. RESULTS: BKAs were performed on 313 patients, of which, 167 underwent preoperative angiography. Thirty-two were excluded due to lack of adequate follow-up leaving a total of 135 patients in the studied population. Diabetes was present in 87%, and 36% had end-stage renal disease. By the study's conclusion, 92% of BKAs had fully healed, with median time-to-healing of 79 days (range 19-1314 days). 60% of patients were ambulatory at 9.5 months. Higher VRO was associated with higher healing rates and lower complications and time-to-healing. The conversion rate of BKA to above-knee amputation (AKA) was 4%. Preoperative popliteal patency was associated with higher postoperative ambulation rates when compared to patients without popliteal flow preoperatively (patent: 71/109, 65%; occluded: 10/26, 40%; p = 0.02) and independently increased the likelihood of postoperative ambulation. CONCLUSIONS: The posterior flap design for BKA works even in the setting of popliteal occlusion. Complication rates are higher in patients with more compromised blood flow, which may ultimately lead to AKA. Given poor ambulation rates in patients who undergo AKA, the results of this study should encourage surgeons to consider a more functional BKA, even in instances when the popliteal artery is occluded.

Comparison of Point-of-Care versus Central Laboratory Testing of Electrolytes, Hemoglobin, and Bilirubin in Neonates.

OBJECTIVE: Electrolyte, hemoglobin, and bilirubin values are routinely reported with point-of-care (POC) testing for blood gases. Results are rapidly available and require a small blood volume. Yet, these results are underutilized due to noted discrepancies between central laboratory (CL) and POC testing. The study aimed to determine the correlation between POC and CL measurement of electrolytes, hemoglobin, and bilirubin in neonates. STUDY DESIGN: Electrolyte, hemoglobin, and bilirubin results obtained from capillary blood over a 4-month period were analyzed. Each CL value was matched with a POC value from the same sample or another sample less than 1-hour apart. Agreement was determined by measuring the mean difference (MD) between paired samples with 95% limits of agreement (LOA) and Lin's concordance correlation (LCC). RESULTS: There were 355-paired sodium/potassium, 139 paired hemoglobin, and 197 paired bilirubin values analyzed. POC sodium values were lower (133.5 ± 5.8 mmol/L) than CL (140.2 ± 5.8 mmol/L), p <0.00001 with poor agreement (LCC = 0.49; MD = 6.7; 95% LOA: -13.6 to 0.14). POC potassium values were lower (4.6 ± 0.98 mmol/L) than CL (4.98 ± 1.24mEq/L), p < 0.0001, but with better concordance and agreement. (LCC = 0.6; MD = 0.4; 95% LOA: -2.3 to 1.4). There were no differences in hemoglobin between POC (14.3 ± 3.2 g/dL) and CL (14.4 ± 3.1 g/dL), p = 0.2 with good LCC (0.93) and in bilirubin values between POC (6.0 ± 3.2 mg/dL) and CL (5.8 ± 3.0 mg/dL), MD = 0.18, and p = 0.07. CONCLUSION: POC Sodium values are lower than CL. POC potassium levels are also lower, but the differences may not be clinically important while hemoglobin and bilirubin levels are similar between POC and CL. As POC potassium, hemoglobin, and bilirubin levels closely reflect CL values, these results can be relied upon to make clinical judgments in neonates. KEY POINTS: · Electrolyte, hemoglobin, and bilirubin are available as POC.. · POC sodium and potassium values are lower than CL results.. · Hemoglobin and bilirubin values are similar between POC and CL..

The impact of statins on wound healing: an ally in treating the highly comorbid patient.

OBJECTIVE: To identify the impact that HMG-CoA reductase inhibitors (statins) use has on wound healing outcomes in patients with comorbidities. METHOD: A retrospective chart review evaluating all new patients presenting to our tertiary wound care centre in 2013 with lower extremity wounds. Patients were divided into two groups depending on whether they took statins or not. Data on wound healing outcomes and wound/patient characteristics were collected. Primary outcomes included healing rate and progression to complete wound healing. Patients were excluded if they had incomplete data or were lost to follow-up before healing status could be confirmed. RESULTS: A total of 194 patients met the inclusion criteria and were allocated to either the statin group (n=89) or to the non-statin group (n=105). Median initial wound size was 0.6cm3 (Interquartile range (IQR): 0.15-2.4) (p=0.684). In the statin group, 54 (60.6%) patients progressed to complete wound healing compared with 47 (44.7%) in the non-statin group (p=0.027). Median rate of wound healing was 6.7×10-3cm3/day (IQR: 1.5×10-3-2.6×10-2) compared with 3.8×10-3cm3/day (IQR: 1.7×10-3-1.3×10-2) in the non-statin group (p=0.773). Increased age and a higher number of comorbidities were reported in the statin group (p<0.001), respectively). A total of seven patients required amputation: five patients in the statin group and two patients in the non-statin group (p=0.250). CONCLUSION: This study revealed increased progression to wound healing in patients who were taking statins. The influence of statins on wound healing is promising, but future trials are needed to justify use of this medication class independent of cardiovascular benefit and exclusively for wound healing.

Double Versus Triple Arthrodesis Fusion Rates: A Systematic Review.

Hindfoot arthrodesis is often required for end-staged deformities, such as posterior tibial tendon dysfunction, osteoarthritis, or rheumatoid arthritis. Although the need for hindfoot arthrodesis is generally accepted in severe deformities, there is a debate whether a double or triple arthrodesis should be performed. The aim of our systematic review is to review the fusion rates and mean time to fusion in double and triple arthrodesis. A total of 184 articles were identified using the keyword search through the database of articles published from 2005 to 2017. After review by 3 physicians, a total of 13 articles met the eligibility criteria. The reason for double or triple arthrodesis within the studies were posterior tibial tendon dysfunction, tarsal coalition, degenerative joint disease, osteoarthritis, rheumatoid arthritis, Charcot Marie Tooth, Multiple Sclerosis, Polio, neuromuscular disorder, cerebral palsy, acrodystrophic neuropathy, clubfoot, post-traumatic, and seronegative arthropathy (spondyloarthritis). Within these 13 studies, there were a total of 343 (6-95) subjects extremities operated on. The overall fusion rate for double arthrodesis was 91.75% (289/315) compared to 92.86% (26/28) triple arthrodesis fusion rate, p value .8370. The mean time to fusion for double arthrodesis was 17.96 ± 7.96 weeks compared to 16.70 ± 8.18 weeks for triple arthrodesis, p value = .8133. There are risks associated with triple arthrodesis including increased surgical times, lateral wound complications, residual deformity, surgical costs and peri-articular arthritis. Given the benefits of double arthrodesis over triple arthrodesis and the nearly equivalent fusion rates and time to fusion, double arthrodesis is an effective alternative to triple arthrodesis. The authors of this systematic review recommend double arthrodesis as the hindfoot fusion procedure of choice.

Risks Factors Associated With Major Lower Extremity Amputation After Vertical Contour Calcanectomy.

The primary aim of the study is to determine risks for major lower extremity amputation after undergoing Vertical Contour Calcanectomy. Subanalysis was performed comparing patients who underwent Vertical Contour Calcanectomy who were fully ambulatory to those who were partially or nonambulatory postoperatively. Within the cohort of 63 patients included in the Vertical Contour Calcanectomy 85.71% (54/63) of patients had diabetes mellitus, 53.97% (34/63) had peripheral arterial disease, and 19.05% (12/63) had Charcot Neuroarthropathy. Multivariate logistic regression, found that (1) patients that underwent primary closure at the time of the Vertical Contour Calcanectomy, were 79.9% more likely (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.04-0.96) to have limb salvage and that (2) female patients were 85.4% less likely compared to male patients (OR 0.15; 95% CI 0.02-0.99) to undergo major lower extremity amputation. Patients with coronary artery disease were 5.2 times more likely (OR 5.18; 95% CI 1.120-23.94) and patients that were nonambulatory preoperatively, were 10.3 times more likely (OR 10.28; 95% CI 1.60-66.26), to be partially or nonambulatory after Vertical Contour Calcanectomy. Primary closure at time of Vertical Contour Calcanectomy significantly decreases the risk of major lower extremity amputation, and diminished preoperative ambulatory status as well as coronary artery disease makes it less likely that patients return to full ambulation after Vertical Contour Calcanectomy.

A systematic review and meta-analysis of endovascular angiosomal revascularization in the setting of collateral vessels.

OBJECTIVE: Endovascular procedures for targeted treatment of lower extremity wounds can be subdivided as direct revascularization (DR), indirect revascularization (IR), and IR via collateral flow (IRc). Although previous systematic reviews assert superiority of DR when compared with IR, the role of collateral vessels in clinical outcomes remains to be defined. This systematic review and meta-analysis aims to define the usefulness of DR, IR, and IRc in treatment of lower extremity wounds with respect to (1) wound healing, (2) major amputation, (3) reintervention, and (4) all-cause mortality. METHODS: A meta-analysis was performed in accordance with PRISMA guidelines. Ovid MEDLINE was queried for records pertaining to the study question using appropriate Medical Subject Heading terms. Studies were limited to those using DR, IR, or IRc as a primary intervention and reporting information on at least one of the primary outcomes of interest. No limitation was placed on year of publication, country of origin, or study size. Studies were assessed for validity using the Newcastle-Ottawa Scale. Study characteristics and patient demographics were collected. Data representing the primary outcomes-wound healing, major amputation, reintervention, and all-cause mortality-were collected for time points ranging from one month to four years following intervention. A meta-analysis on sample size-weighted data assuming a random effects model was performed to calculate odds ratios (ORs) for the four primary outcomes at various time points. RESULTS: We identified 21 studies for a total of 4252 limbs (DR, 2231; IR, 1647; IRC, 270). Overall wound healing rates were significantly superior for DR (OR, 2.45; P = .001) and IRc (OR, 8.46; P < .00001) compared with, IR with no significant difference between DR and IRc (OR, 1.25; P = .23). The overall major amputation rates were significantly superior for DR (OR, 0.48; P < .00001) and IRc (OR, 0.44; P = .006) compared with IR, with DR exhibiting significantly improved rates compared with IRc (OR, 0.51; P = .01). The overall mortality rates showed no significant differences between DR (OR, 0.89; P = .37) and IRc (OR, 1.12; P = .78) compared with IR, with no significant difference between DR and IRc (OR, 0.54; P = .18). The overall reintervention rates showed no significant difference between DR and IR (OR, 1.05; P = .81), with no studies reporting reintervention outcomes for IRc. CONCLUSIONS: Both DR and IRc offer significantly improved wound healing rates and major amputation rates compared with IR when used to treat critical limb ischemia. Although DR should be the preferred method of revascularization, IRc can offer comparable outcomes when DR is not possible. This analysis was limited by a small sample size of IRc limbs, a predominance of retrospective studies, and variability in outcome definitions between studies.

Virtual reality for pain management in advanced heart failure: A randomized controlled study.

BACKGROUND: Hospitalized patients with advanced heart failure often experience acute and/or chronic pain. While virtual reality has been extensively studied across a wide range of clinical settings, no studies have yet evaluated potential impact on pain management on this patient population. AIM: To investigate the impact of a virtual reality experience on self-reported pain, quality-of-life, general distress, and satisfaction compared to a two-dimensional guided imagery active control. DESIGN: Single-center prospective randomized controlled study. The primary outcome was the difference in pre- versus post-intervention self-reported pain scores on a numerical rating scale from 0 to 10. Secondary outcomes included changes in quality-of-life scores, general distress, and satisfaction with the intervention. SETTING/PARTICIPANTS: Between October 2018 and March 2020, 88 participants hospitalized with advanced heart failure were recruited from an urban tertiary academic medical center. RESULTS: Participants experienced significant improvement in pain score after either 10 minutes of virtual reality (change from pre- to post -2.9 ± 2.6, p < 0.0001) or 10 minutes of guided imagery (change from pre- to post -1.3 ± 1.8, p = 0.0001); the virtual reality arm experienced a 1.5 unit comparatively greater reduction in pain score compared to guided imagery (p = 0.0011). Total quality-of-life and general distress scores did not significantly change for either arm. Seventy-eight participants (89%) responded that they would be willing to use the assigned intervention again. CONCLUSION: Virtual reality may be an effective nonpharmacologic adjuvant pain management intervention in hospitalized patients with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov database (NCT04572425).

Perioperative outcomes following pelvic floor reconstruction in women with hereditary disorders of connective tissue: a retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Women with hereditary disorders of connective tissue (HDCT) are at increased risk of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). We hypothesized that patients would have increased incidence and severity of perioperative complications up to 6 weeks after surgeries for POP/SUI. Secondary objectives were to compare pre- and post-operative pelvic floor symptoms and anatomical support as well as pelvic floor disorder recurrence. METHODS: In this multi-center retrospective cohort study, we identified patients with HDCTs by patient history and ICD-9 codes over an 11-year period. Controls without HDCTs were matched 2:1 to the primary POP or SUI procedure and surgeon. Demographic characteristics, perioperative pelvic floor information and complications were collected. A sample size of 65 HDCT patients and 130 controls was calculated to detect a 20% difference in complications with 80% power and alpha of 0.05. RESULTS: We identified 59 HDCT patients and 118 controls. Of the women with HDCTs, 49% had Ehlers-Danlos, 22% joint hypermobility syndrome, 15% Marfan syndrome, and 14% had others. Compared with controls, HDCT patients had more total perioperative complications (46% vs 22%, p = 0.002); an age-adjusted relative risk of complications was 1.4 (CI 0.7-2.6). HDCT patients had more Clavien-Dindo grades I and II complications (p = 0.02, 0.03) and more hospital readmissions (14% vs 3%, p = 0.01) than controls. There was no difference in the incidence of specific complications nor was there a difference in recurrence of POP (10%) or SUI (11%) between groups. CONCLUSIONS: Patients with HDCTs had more Clavien-Dindo grade I and II complications following pelvic floor reconstructive surgery and more readmissions.

Complications of Charcot Reconstruction in Patients With Peripheral Arterial Disease.

The primary aim was to determine the rate of complications in patients with peripheral arterial disease and diabetic Charcot neuroarthropathy who underwent osseous reconstruction. Complications included delayed healing, dehiscence, and major lower extremity amputation. A review of patients with Charcot neuroarthropathy requiring reconstruction secondary to ulceration or acute infection was performed. Descriptive analysis compared outcomes between those with and without peripheral arterial disease. Bivariate analysis and multivariate logistic regression were analyzed for delayed healing, dehiscence, and major amputation. In a cohort of 284 patients with diabetic Charcot neuroarthropathy who underwent osseous reconstruction, the rate of peripheral arterial disease was 20.8% (59/284). Bivariate analysis for delayed healing found hypertension (p = .0352), peripheral arterial disease (p = .0051), and smoking history (p = .0276) to be statistically significant factors. Delayed healing was 2.012 times more likely in the presence of peripheral arterial disease [OR 2.012 (95% CI 1.088-3.720)]. Bivariate analysis for major lower extremity amputation found renal disease (0.0003) (renal disease: ESRD and CKD) and peripheral arterial disease (0.0001) to be statistically significant factors. Major amputation was 4.414 times more likely in the presence of peripheral arterial disease [OR 4.414 (95% CI 2.087-9.334)]. Peripheral arterial disease was identified in 20.8% (59/284) of diabetic patients who underwent Charcot osseous reconstruction. Peripheral arterial disease increased the risk of delayed healing by 2.012 fold, and increased the risk of major lower extremity amputation by 4.414 fold. The rates of complications in patients with peripheral arterial disease were significantly higher than those without peripheral arterial disease who underwent osseous reconstruction.

Comparison of Novel Immunoassay With Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) for Therapeutic Drug Monitoring of Clozapine.

BACKGROUND: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia. Although serum clozapine levels can help guide treatment, they are underutilized owing to requirements for frequent venous blood draws and lack of immediate results. METHODS: Clozapine levels measured with a novel immunoassay technology (which enables point-of-care development) were compared with those measured by standard liquid chromatography/tandem mass spectrometry (LC-MS/MS). Frozen serum aliquots of 117 samples (N = 48 patients with schizophrenia on clozapine; N = 24 patients with schizophrenia not on clozapine; N = 45 healthy controls) were sent to a national reference laboratory (NRL) for clozapine level determination by LC-MS/MS, and matching samples were subjected to novel immunoassay (3 runs). At a later date, another frozen aliquot from the same date was sent to the NRL for repeat testing. RESULTS: The NRL obtained 18 false-positive clozapine results (mean 42.39 ± 32.06, range 21-159 ng/mL) in participants not on clozapine (N = 3) and healthy controls (N = 15). The immunoassay showed no false-positive clozapine results. The clozapine levels were correlated between both assays (r = 0.84, P < 0.0001), despite 16% higher clozapine levels with immunoassay (482.08 ± 270.88 ng/mL immunoassay, 414.98 ± 186.29 ng/mL LC-MS/MS [P = 0.03]). Agreement analysis using concordance correlation coefficient (CCC) for LC-MS/MS of the 2 aliquots yielded CCC = 0.869; 95% confidence interval = 0.690-0.970, whereas higher agreement results were observed for the 3 runs of immunoassay (CCC = 0.99; 95% confidence interval = 0.979-0.997). CONCLUSIONS: The lack of false positives observed with immunoassay, higher repeat performance agreement, and good correlation with LC-MS/MS may indicate the more robust performance of immunoassay than that of LC-MS/MS clozapine-level determination.

Charcot Reconstruction: Outcomes in Patients With and Without Diabetes.

The objective of this study is to compare risk adjusted matched cohorts of Charcot neuroarthropathy patients who underwent osseous reconstruction with and without diabetes. The 2 groups were matched based on age, body mass index, hypertension, history of end-stage renal disease, and peripheral arterial disease. Bivariate analysis was performed for preoperative infection, location of Charcot breakdown, and post reconstruction outcomes, in patients with a minimum of 1 year follow-up period. Through bivariate analysis, presence of preoperative ulceration (p = .0499) was found to be statistically more likely in the patients with diabetes; whereas, delayed osseous union (p = .0050) and return to ambulation (p ≤ .0001) was statistically more likely in patients without diabetes. The nondiabetic Charcot patients were 17.6 folds more likely to return to ambulation (odds ratio [OR] 17.6 [95% confidence interval {CI} {3.5-87.6}]), and 16.4 folds more likely to have delayed union (OR 16.4 [95% CI {1.9-139.6)]). Subanalysis compared well-controlled diabetic and nondiabetic Charcot neuroarthropathy patients for same factors. Multivariate analysis, in the subanalysis, found return to ambulation was 15.1 times likely to occur in the nondiabetic CN cohort (OR 15.1 [95% CI 1.3-175.8]) compared to the well-controlled diabetic CN cohort.

Prevalence and Predictors of Pulmonary Embolism in Hospitalized Patients with Syncope.

OBJECTIVES: Approximately one in six patients hospitalized with syncope have pulmonary embolism (PE), according to the PE in Syncope Italian Trial study. Subsequent studies using administrative data have reported a PE prevalence of <3%. The aim of the study was to determine the prevalence and predictors of PE in hospitalized patients with syncope. METHODS: We retrospectively reviewed the records of patients who were hospitalized in the MedStar Washington Hospital Center between May 1, 2015 and June 30, 2017 with deep venous thrombosis, PE, and syncope. Only patients who presented to the emergency department with syncope were included in the final analysis. PE was diagnosed by either positive computed tomographic angiography or a high-probability ventilation-perfusion scan. Univariate and multivariate logistic regressions were used to assess the associations between clinical variables and the diagnosis of PE in patients with syncope. RESULTS: Of the 408 patients hospitalized with syncope (mean age, 67.5 years; 51% men [N = 208]), 25 (6%) had a diagnosis of PE. Elevated troponin levels (odds ratio 6.6, 95% confidence interval 1.9-22.9) and a dilated right ventricle on echocardiogram (odds ratio 6.9, 95% confidence interval 2.0-23.6) were independently associated with the diagnosis of PE. Age, active cancer, and history of deep venous thrombosis were not associated with the diagnosis of PE. CONCLUSIONS: The prevalence of PE in this study is approximately one-third of the reported prevalence in the PE in Syncope Italian Trial study and almost three times the value reported in administrative data-based studies. PE should be suspected in patients with syncope and elevated troponin levels or a dilated right ventricle on echocardiogram.