Reconstruction Considerations Following Complete Excision of Mucoid-Degenerated Anterior Cruciate Ligament: A Retrospective Study.

INTRODUCTION: Mucoid degeneration (MD) of the anterior cruciate ligament (ACL) is an unusual cause of knee pain and restricted movement, predominantly affecting the middle-aged population. Arthroscopic partial or total debridement of the mucoid ACL is the surgical treatment of choice. However, little is discussed in the literature regarding subsequent knee instability and functional outcomes following complete ACL excision. METHODS: A retrospective study was conducted on patients who underwent arthroscopic total ACL excision for mucoid ACL. Pre- and post-operatively, the Tegner-Lysholm score, the International Knee Documentation Committee (IKDC) Subjective Knee Form, and subjective functional instability were used to grade the clinical outcomes. RESULTS: Ten out of the 13 patients who underwent complete ACL excision were available for evaluation. All patients presented with knee pain on deep flexion or extension with a painfully limited range of motion. Post-operatively, all patients were relieved of their original pain and dysfunction. The mean post-operative IKDC and Tegner-Lysholm scores were 74.96 and 83.6, respectively. All patients had a Lachman test positive, while only two had a grade 1 pivot shift test positive. Two patients had occasional functional instability only after strenuous exercises. None of the patients underwent subsequent ACL reconstruction. CONCLUSION: All patients reported improved functional outcomes. Only two out of 10 reported occasional instability during strenuous activity. Therefore, complete debridement of mucoid ACL in sedentary patients is safe and efficacious. However, active young patients may experience instability and require ACL reconstruction if it hinders their daily activities.

Structural insights into the interactions of repositioning and known drugs for Alzheimer's disease with hen egg white lysozyme by MM-GBSA.

Six drugs (dapsone, diltiazem, timolol, rosiglitazone, mesalazine, and milnacipran) that were predicted by network-based polypharmacology approaches as potential anti-Alzheimer's drugs, have been subjected in this study for in silico and in vitro evaluation to check their potential against protein fibrillation, which is a causative factor for multiple diseases such as Alzheimer's disease, Parkinson's disease, Huntington disease, cardiac myopathy, type-II diabetes mellitus and many others. Molecular docking and thereafter molecular dynamics (MD) simulations revealed that diltiazem, rosiglitazone, and milnacipran interact with the binding residues such as Asp52, Glu35, Trp62, and Asp101, which lie within the fibrillating region of HEWL. The MM-GBSA analysis revealed -7.86, -5.05, and -10.29 kcal/mol as the binding energy of diltiazem, rosiglitazone, and milnacipran. The RMSD and RMSF calculations revealed significant stabilities of these ligands within the binding pocket of HEWL. While compared with two reported ligands inhibiting HEWL fibrillation, milnacipran depicted almost similar binding potential with one of the known ligands (Ligand binding affinity -10.66 kcal/mol) of HEWL. Furthermore, secondary structure analyses revealed notable inhibition of the secondary structural changes with our candidate ligand; especially regarding retention of the 3/10 α-helix both by DSSP simulation, Circular dichroism, and FESEM-based microscopic image analyses. Taking further into experimental validation, all three ligands inhibited fibrillation in HEWL in simulated conditions as revealed by blue shift in Congo red assay and later expressing percentage inhibition in ThioflavinT assay as well. However, dose-dependent kinetics revealed that the antifibrillatory effects of drugs are more pronounced at low protein concentrations.Communicated by Ramaswamy H. Sarma.

Modeling Individual Differences in Food Metabolism through Alternating Least Squares.

Understanding how macronutrients (e.g., carbohydrates, protein, fat) affect blood glucose is of broad interest in health and dietary research. The general effects are well known, e.g., adding protein and fat to a carbohydrate-based meal tend to reduce blood glucose. However, there are large individual differences in food metabolism, to where the same meal can lead to different glucose responses across individuals. To address this problem, we present a technique that can be used to simultaneously (1) model macronutrients' effects on glucose levels over time and (2) capture inter-individual differences in sensitivity to macronutrients. The model assumes that each macronutrient adds a basis function to the differences in macronutrient metabolism. The technique performs a linear decomposition of glucose responses, alternating between estimating the macronutrients' effect over time and capturing an individual's sensitivity to macronutrients. On an experimental dataset containing glucose responses to a variety of mixed meals, the technique is able to extract basis functions for the macronutrients that are consistent with their hypothesized effects on PPGRs, and also characterize how macronutrients affect individuals differently.

Predicting the Macronutrient Composition of Mixed Meals From Dietary Biomarkers in Blood.

Diet monitoring is an essential intervention component for a number of diseases, from type 2 diabetes to cardiovascular diseases. However, current methods for diet monitoring are burdensome and often inaccurate. In prior work, we showed that continuous glucose monitors (CGMs) may be used to predict meal macronutrients (e.g., carbohydrates, protein, fat) by analyzing the shape of the post-prandial glucose response. In this study, we examine a number of additional dietary biomarkers in blood by their ability to improve macronutrient prediction, compared to using CGMs alone. For this purpose, we conducted a nutritional study where (n = 10) participants consumed nine different mixed meals with varied but known macronutrient amounts, and we analyzed the concentration of 33 dietary biomarkers (including amino acids, insulin, triglycerides, and glucose) at various times post-prandially. Then, we built machine learning models to predict macronutrient amounts from (1) individual biomarkers and (2) their combinations. We find that the additional blood biomarkers provide complementary information, and more importantly, achieve lower normalized root mean squared error (NRMSE) for the three macronutrients (carbohydrates: 22.9%; protein: 23.4%; fat: 32.3%) than CGMs alone (carbohydrates: 28.9%, t(18) =1.64, p =0.060; protein: 46.4%, t(18) =5.38, p 0.001; fat: 40.0%, t(18) =2.09, p =0.025). Our main conclusion is that augmenting CGMs to measure these additional dietary biomarkers improves macronutrient prediction performance, and may ultimately lead to the development of automated methods to monitor nutritional intake. This work is significant to biomedical research as it provides a potential solution to the long-standing problem of diet monitoring, facilitating new interventions for a number of diseases.

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART II-Surgical Evaluation and Treatment.

PURPOSE: Surgical therapies for symptomatic bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) are many, and vary from minimally invasive office based to high-cost operative approaches. This Guideline presents effective evidence-based surgical management of male lower urinary tract symptoms secondary/attributed to BPH (LUTS/BPH). See accompanying algorithm for a detailed summary of procedures (figure[Figure: see text]). MATERIALS/METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible studies published between January 2007 and September 2020, which includes the initial publication (2018) and amendments (2019, 2020). The Team also reviewed articles identified by Guideline Panel Members. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). RESULTS: Twenty-four guideline statements pertinent to pre-operative and surgical management were developed. Appropriate levels of evidence and supporting text were created to direct urologic providers towards suitable and safe operative interventions for individual patient characteristics. A re-treatment section was created to direct attention to longevity and outcomes with individual approaches to help guide patient counselling and therapeutic decisions. CONCLUSION: Pre-operative and surgical management of BPH requires attention to individual patient characteristics and procedural risk. Clinicians should adhere to recommendations and familiarize themselves with criteria that yields the highest likelihood of surgical success when choosing a particular approach for a particular patient.

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART I-Initial Work-up and Medical Management.

PURPOSE: Benign prostatic hyperplasia (BPH) is a histologic diagnosis describing proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and severity of lower urinary tract symptoms (LUTS) in aging men are progressive and impact the health and welfare of society. This revised Guideline provides a useful reference on effective evidence-based management of male LUTS/BPH. See the accompanying algorithm for a summary of the procedures detailed in the Guideline (figures 1 and 2[Figure: see text][Figure: see text]). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible English language studies published between January 2008 and April 2019, then updated through December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: Nineteen guideline statements pertinent to evaluation, work-up, and medical management were developed. Appropriate levels of evidence and supporting text were created to direct both primary care and urologic providers towards streamlined and suitable practices. CONCLUSIONS: The work up and medical management of BPH requires attention to individual patient characteristics, while also respecting common principles. Clinicians should adhere to recommendations and familiarize themselves with standards of BPH management.

Worsening disability status in multiple sclerosis predicts urologic complications.

PURPOSE: Multiple sclerosis (MS) causes voiding dysfunction and might predispose to urologic complications. However, long-term complications and risk factors for complications are unknown. We aim to assess long-term changes in voiding function and to determine risk factors for urologic complications during MS follow-up. METHODS: We analyzed the records of MS patients and recorded baseline and follow-up voiding symptoms, urodynamic (UDS) findings, Expanded Disability Status Scale (EDSS), serum blood studies, imaging, and complications. T test and Chi-square test were used to determine statistical significance using a two-tailed p value < 0.05. We assessed complication-free survival using Kaplan-Meier curves and performed multiple variable Cox proportional hazard models to estimate hazard ratios predicting complications for various independent variables. RESULTS: 126 women and 35 men with MS were followed for a median of 9.7 years (IQR 4.3-13). Mean age at MS diagnosis was 36.7 with a mean EDSS of 3.2. During follow-up, EDSS progressed to a mean of 5.5. In addition, at least one complication occurred in 60.2% and major complications were present in 16.7%. After multivariable analysis, EDSS progression ≥ 2.0 (p = 0.003), follow-up EDSS ≥ 6.0 (p = 0.01), use of intermittent catheterization (p < 0.001) and urinary reconstruction with continent catheterizable stoma (p = 0.009) were significantly related to an increased hazard for any complications. CONCLUSION: Upper tract changes and other major complications were uncommon. Complications were related to MS progression, resultant increase in total disability, and the need for intervention to maintain functional continence. Lower tract infections occurred more frequently in patients with the need for catheterization.

Long-term (>5 years) outcomes of patients implanted with artificial urinary sphincter: A single-center experience.

INTRODUCTION: This study is conducted to evaluate the long-term outcomes, including effectiveness and complications, of artificial urinary sphincter (AUS) implantation in men with primarily stress urinary incontinence. MATERIALS AND METHODS: Consecutive patients with complete data sets and a continuous follow-up with the device in place for 5 years or more were included. We analyzed effectiveness through pads per day use, and complications were assessed based on device revisions and explantations. Various risk factors for revisions were evaluated and revision free-survival at 15 years was estimated. RESULTS: Thirty-four male patients were implanted and followed for a mean of 116.5 months (range: 60-285). Mean pads per day use was significantly decreased from 3.6 at baseline to 0.6 at 1 year, 1.1 at 5 years, and 1.06 at last visit (P < 0.0001). During follow-up, 12 patients (35%) required between 1 and 3 device revisions and 1 (3%) required 5. The device revision-free survival was 76% (confidence interval [CI] 58%-87%) at 5 years and 56% (CI 32%-75%) at 15 years. A higher mean number of dilations or incisions for bladder neck contractures was a statistically significant risk factor for revisions in univariate analysis (odds ratio 1.8; 95% CI 1.02-3.2). No other significant risk factors for revisions were found. Explantations were performed in four patients for device erosion at 60, 69, 153, and 200 months. CONCLUSIONS: The AUS provides excellent long-term outcomes with continued improvement in continence rates and <50% of patients requiring revisions at 15 years. The previous history of bladder neck contractures and dilations may predispose to an increased rate of revisions.

Expectant long-term follow-up of patients with chronic urinary retention.

AIMS: To describe urologic complications in patients with chronically elevated post-void residual (PVR) volumes and to evaluate other related risk factors during a long-term follow-up in patients managed conservatively. METHODS: Non-neurogenic patients who refused surgical intervention of the prostate and had PVR volumes >300 mL on two or more separate occasions at least 6 months apart were included. We followed this cohort over time, recorded complications and evaluated risk factors for complications. RESULTS: Twenty-eight men with a mean age of 74 were followed for a median of 56 months (IQR: 26-101 months); 26 had benign prostatic hyperplasia with a median prostate size of 55 cc. Baseline median PVR was 468 cc (IQR: 395-828) and follow-up median PVR was 508 cc (IQR: 322-714). During follow-up, 13 patients (46%) had at least one complication with acute urinary retention being the most common occurring in 10 patients (36%) with 15 episodes. Other complications presented in less than 15%, and no patients developed permanent renal insufficiency. Patients with prostate size ≥ 100 cc had significantly higher total number of acute retention episodes (P-value: 0.01). CONCLUSIONS: Although the presence of CUR could commonly predispose to episodes of acute retention, severe complications are infrequent although present. Additionally, prostate size may play a role in increasing some adverse outcomes. With proper counseling about different complications, patients with retention who denied surgical treatment can be safely followed for at least 5 years without renal deterioration.

A Bilateral Metachronous Mesothelioma of the Tunica Vaginalis.

This is a unique case of bilateral metachronous testicular mesothelioma of the tunica vaginalis. Testicular mesothelioma is a rare entity found in patients with or without asbestos occupational exposure. The tumor most commonly presents as a unilateral testicular mass. More rare presentations include bilateral synchronous or metachronous tumors. Treatment is with surgical resection and prognosis is not generally favorable. The benefits of adjuvant therapy with radiation or chemotherapy remain unknown and further studies are needed.

Electrical neuromodulation in the management of lower urinary tract dysfunction: evidence, experience and future prospects.

Lower urinary tract dysfunction (LUTD) is common and causes a spectrum of morbidity and decreased quality of life (QoL) for patients. LUTD can range from urinary retention to urge incontinence, and includes a variety of syndromes, with the most common and widely recognized being overactive bladder (OAB). The classic treatments of LUTD and OAB comprise different strategies including behavioral therapies, medications and minimally invasive or invasive surgical procedures. Generally, once patients have tried behavioral modifications and oral medical therapy, and have not experienced adequate relief of their symptoms, the next step is to consider minimally invasive therapies. In the last two decades since FDA approval, sacral nerve stimulation (SNS) has become an accepted intervention, with increasing use and evidence of effectiveness for LUTD, specifically OAB and non-obstructive urinary retention. SNS has shown both objective and subjective improvement in voiding symptoms in several randomized controlled trials (RCTs) when compared to sham or standard medical therapy. The main limitations for more extensive use include relatively high cost, implantation of a device and possibly reoperation secondary to adverse events (AE). Percutaneous tibial nerve stimulation (PTNS) is a less invasive, less direct and less expensive method for neuromodulation, which has also shown effectiveness in several randomized and non-randomized trials, including comparable improvement rates to anticholinergics in OAB management. However, the efficacy of PTNS is only maintained for a short period after the stimulation is delivered. This technique has a much lower rate of AE compared to SNS, but with the inconvenience of weekly visits for stimulation, although implantable devices are on the horizon. In this article we review the mechanism of action, indications, effectiveness and complications related to SNS and PTNS therapy for LUTD.

Patient Characteristics and Perioperative Outcomes of Female Urethral Diverticulectomy: Analysis of a Multi-Institutional Prospective Database.

OBJECTIVE: To assess the patient and perioperative characteristics of urethral diverticulectomy using a large multi-institutional prospectively collected database. MATERIALS AND METHODS: Female patients were identified using the American College of Surgeons National Surgical Quality Improvement Program participant user files (2007-2012) and current procedural terminology codes for urethral diverticulectomy (53,230). Preoperative variables and 30-day complications were examined. RESULTS: Urethral diverticulectomies were performed on 122 females during the study period. The cohort was relatively healthy; 80% of patients had an American Society of Anesthesiologists score of 1 or 2. The majority of procedures were performed in an outpatient setting (82%). The median procedure length was 77.5 minutes (interquartile range: 50.5-112.5), and the median length of stay was 0 days (interquartile range: 0-1). The overall 30-day complication rate was 3.3% (n = 4): 3 patients developed urinary tract infections (UTIs) and 1 patient developed both a UTI and a superficial wound infection. CONCLUSION: To our knowledge, our study represents the largest multi-institutional cohort of patients having undergone urethral diverticulectomy. The patients requiring this intervention were relatively healthy, and the procedure itself was short, allowing most patients to be discharged within 24 hours. The 30-day complication rate was very low, with UTI being the most common complication. Thus, patients can continue to be confidently counseled that urethral diverticulectomy is a safe procedure with very few perioperative complications.

Electrical and mechanical office-based neuromodulation.

Overactive bladder (OAB) is commonly encountered in urologic practice. Treatment algorithms begin with conservative therapy and pharmacotherapy with antimuscarinics. Some patients do not receive adequate relief from these methods or they do not tolerate side effects from pharmacotherapy. A test stimulation for sacral neuromodulation and percutaneous tibial nerve stimulation are office-based techniques that are commonly used as the next step in the algorithm of care in patients with OAB. These techniques are efficacious and approved by the Food and Drug Administration for treatment of overactive bladder and its associated symptoms.