Decreased Opioid Use and Equivalent Pain Score Outcomes After Robotic Urologic Surgery Using a Simplified Opioid Minimization Protocol: A Safety-Net Hospital Experience.

INTRODUCTION: We aimed to implement a simplified opioid minimization (OM) protocol after robotic urologic surgery in a safety-net hospital to decrease opioid consumption without compromising patient-reported pain or satisfaction. METHODS: Robotic urologic surgery was performed in 103 consecutive patients at a safety-net hospital. An opioid control (OC) cohort was established from January to May 2021, and the OM protocol was implemented from June to October 2021. On postoperative day (POD) 2 and POD7, a validated survey was used to assess pain and satisfaction. Opioid dispensation records were queried from the Prescription Monitoring Program. Outcomes were compared by univariate methods. RESULTS: There were no demographic differences between the OM (n = 45) and OC (n = 35) cohorts. Total opioids received within 30 days of surgery decreased by 68% in the OM vs OC cohort (median [IQR] 32.5 [7.5-65] vs 100 [30-173] morphine milligram equivalents, P < .001). The median amount of opioids prescribed at discharge for the OM cohort was 0 (IQR:0-0) vs 75 morphine milligram equivalents (IQR:0-112.5) for the OC cohort (P < .001). Pain severity did not differ between cohorts on POD2 (median [IQR]: OM=3/10 [2-5], OC=3.5/10 [2-6]; P = .5) or POD7 (median [IQR]: OM=2/10 [0-3], OC=1/10 [0-3]; P = .8), and POD7 satisfaction with pain management remained high for both cohorts (P = .8). CONCLUSIONS: Our simplified OM protocol decreased total opioid use after robotic urologic surgery by 68% without compromising pain or satisfaction.

Steerable Ureteroscopic Renal Evacuation (SURE) for Large Renal Stones: A Multi-Institutional Center Study.

BACKGROUND: The results of a recent pilot study suggest that steerable ureteroscopic renal evacuation (SURE) is safe and more effective in stone removal than basketing following laser lithotripsy. The objective of this retrospective study was to further assess the safety and efficacy of SURE using the CVAC® Aspiration System (Calyxo, Inc., Pleasanton, CA) in patients with large stone burdens. MATERIALS AND METHODS: Patients with a baseline stone burden of ≥10 mm who underwent SURE were identified. Subject demographics, secondary procedures, complications, and stone clearance (defined as percent baseline volume reduction) were evaluated. Sub-analyses were performed to explore patients identified as high-risk for percutaneous nephrolithotomy (PCNL) because 1) they were on anticoagulation or antiplatelet therapy at the time of procedure, or 2) they had limited mobility due to neurological conditions. RESULTS: Identified patients (N=43) had a mean pre-operative stone burden of 29±12 mm and mean stone volume of 3,092±5,002 mm3. Approximately one-half of patients (n=24, 55.8%) had computerized tomography (CT) imaging at follow-up, and of those, eight (33.3%) had no residual stones, 22 (91.7%) had >90% stone clearance, 23 (95.8%) had >80% stone clearance and 24 (100%) had >60% stone clearance. Stone clearance based on baseline stone burden varied between 93.8% and 98.9%. At baseline, 21 patients were anticipated to require staged ureteroscopy; however, only two of those (9.5%) needed secondary procedures. High-risk patients (n=22) were on anticoagulation or antiplatelet therapy (n=12) or had neurologic conditions (n=10). Stone clearance was 97% among patients in the anticoagulated cohort with postoperative CT imaging, and 83% in patients with neurologic conditions. There were no device-related complications and no post-operative admissions. CONCLUSIONS: The CVAC® Aspiration System is safe and effective for treating large stone burdens, including in high-risk patients, and may decrease the need for PCNL or secondary procedures.

Urethral Injuries: Diagnostic and Management Strategies for Critical Care and Trauma Clinicians.

Urologic trauma is a well-known cause of urethral injury with a range of management recommendations. Retrograde urethrogram remains the preferred initial diagnostic modality to evaluate a suspected urethral injury. The management thereafter varies based on mechanism of injury. Iatrogenic urethral injury is often caused by traumatic catheterization and is best managed by an attempted catheterization performed by an experienced clinician or suprapubic catheter to maximize urinary drainage. Penetrating trauma, most commonly associated with gunshot wounds, can cause either an anterior and/or posterior urethral injury and is best treated with early operative repair. Blunt trauma, most commonly associated with straddle injuries and pelvic fractures, can be treated with either early primary endoscopic realignment or delayed urethroplasty after suprapubic cystostomy. With any of the above injury patterns and treatment options, a well thought out and regimented follow-up with a urologist is of utmost importance for accurate assessment of outcomes and appropriate management of complications.

Appropriateness Criteria for Ureteral Stent Omission following Ureteroscopy for Urinary Stone Disease.

Objective: To bridge the gap between evidence and clinical judgement, we defined scenarios appropriate for ureteral stent omission after uncomplicated ureteroscopy (URS) using the RAND/UCLA Appropriateness Method (RAM). We retrospectively assessed rates of appropriate stent omission, with the goal to implement these criteria in clinical practice. Methods: A panel of 15 urologists from the Michigan Urological Surgery Improvement Collaborative (MUSIC) met to define uncomplicated URS and the variables that influence stent omission decision-making. Over two rounds, they scored clinical scenarios for Appropriateness Criteria (AC) for stent omission based on a combination of variables. AC were defined by median scores: 1 to 3 (inappropriate), 4 to 6 (uncertain), and 7 to 9 (appropriate). Multivariable analysis determined the association of each variable with AC scores. Uncomplicated URS cases in the MUSIC registry were assigned AC scores and stenting rates assessed. Results: Seven variables affecting stent decision-making were identified. Of the 144 scenarios, 26 (18%) were appropriate, 88 (61%) inappropriate, and 30 (21%) uncertain for stent omission. Most scenarios appropriate for omission were pre-stented (81%). Scenarios with ureteral access sheath or stones >10mm were only appropriate if pre-stented. Stenting rates of 5,181 URS cases correlated with AC scores. Stents were placed in 61% of cases appropriate for omission (practice range, 25% to 98%). Conclusion: We defined objective variables and AC for stent omission following uncomplicated URS. AC scores correlated with stenting rates but there was substantial practice variation. Our findings demonstrate that the appropriate use of stent omission is underutilized.

The Impact of a Multimodal Sport Science-Based Prehabilitation Program on Clinical Outcomes in Abdominal Cancer Patients: A Cohort Study.

BACKGROUND: The potential for prehabilitation programs to impact clinical outcomes is uncertain in abdominal cancer patients due to the short window of time to intervene and the weakened state of the patients. To improve the effectiveness of prehabilitation intervention, a multimodal sports science approach was implemented. METHODS: Prior to cancer-related surgery, 21 patients participated in a 4-week exercise and nutrition prehabilitation program comprised of blood flow restriction exercise (BFR) and a sports nutrition supplement. Retrospective data of 71 abdominal cancer patients who underwent usual preoperative care was used as a comparator control group (CON). At 90 days post-surgery, clinical outcomes were quantified. RESULTS: Prehabilitation was associated with a shorter length of hospital stay (P = .02) with 5.5 fewer days (4.7 ± 2.1 vs 10.2 ± 1.2 days in CON) and decreased incidence of any complications (P = .03). Prehabilitation was not related to incidence of serious complications (P = .17) or readmission rate (P = .59). The prehabilitation group recorded 58% more steps on day 5 after surgery (P = .043). DISCUSSION: A 4-week home-based prehabilitation program composed of BFR training and sports nutrition supplementation was effective in reducing postoperative complications and length of hospital stay in older patients with abdominal cancer.ClinicalTrials.gov Identifier: NCT04073381.

Opiate Prescriptions Vary among Common Urologic Procedures: A Claims Dataset Analysis.

Objectives: This study aimed to better understand differences in the total days' supply and fills of common opiates following urologic procedures. Materials and Methods: The Truven Health MarketScan® database was used to extract CPT codes from adults 18 years or older who underwent a urologic procedure with 90-day follow-up from 2012−2015 within the Austin−Round Rock, Texas metropolitan service area. A multivariate analysis and first hurdle modeling with a logistic outcome for any opiates was used to (1) assess differences in opioid prescribing patterns, (2) investigate opioid prescription outcomes, and (3) explore variability among opiate prescription patterns across seven urologic procedure categories. Results: Among the 2312 patients who met the inclusion criteria, 23.7% received an opiate, with an average total day's supply of 6.20 (range 2.61−10.59). The proportion of patients receiving opiates varied significantly by procedure type (p = 0.028). Patients that had reconstructive procedures had the highest proportion of any opiates and the highest number of mean opiate prescriptions among the seven procedure categories (42% received opiates, p = 0.028, mean opiate prescriptions were 1.0 among all patients, p = 0.026). After adjustments, the multivariate analysis demonstrated that patients undergoing reconstructive procedures filled more opiate prescriptions (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.00−3.50, p = 0.05) compared to other subcategories. Of those that received opiates, reconstructive patients had a shorter time to fills (mean −18.4 days, CI −8.40 to −28.50, p < 0.001). Conclusion: Patients undergoing reconstructive procedures are prescribed and fill more opiates compared to other common urological procedures. The standardization and implementation of postoperative pain regimens may help curtail this variability.

A Mobile App With Multimodality Prehabilitation Programs for Patients Awaiting Elective Surgery: Development and Usability Study.

BACKGROUND: Complying with a prehabilitation program is difficult for patients who will undergo surgery, owing to transportation challenges and a limited intervention time window. Mobile health (mHealth) using smartphone apps has the potential to remove barriers and improve the effectiveness of prehabilitation. OBJECTIVE: This study aimed to develop a mobile app as a tool for facilitating a multidisciplinary prehabilitation protocol involving blood flow restriction training and sport nutrition supplementation. METHODS: The app was developed using "Appy Pie," a noncoding app development platform. The development process included three stages: (1) determination of principles and requirements of the app through prehabilitation research team meetings; (2) app prototype design using the Appy Pie platform; and (3) app evaluation by clinicians and exercise and fitness specialists, technical professionals from Appy Pie, and non-team-member users. RESULTS: We developed a prototype of the app with the core focus on a multidisciplinary prehabilitation program with accessory features to improve engagement and adherence to the mHealth intervention as well as research-focused features to evaluate the effects of the program on frailty status, health-related quality of life, and anxiety level among patients awaiting elective surgery. Evaluations by research members and random users (n=8) were consistently positive. CONCLUSIONS: This mobile app has great potential for improving and evaluating the effectiveness of the multidisciplinary prehabilitation intervention in the format of mHealth in future.

Prehabilitation program composed of blood flow restriction training and sports nutrition improves physical functions in abdominal cancer patients awaiting surgery.

INTRODUCTION: The impact of prehabilitation remains controversial due to a short presurgical waiting period and the diminished capacity of the patient population. A strategy to augment and optimize the effectiveness of prehabilitations for abdominal cancer patients may be found in the unlikely field of sport science. We investigated the use of blood flow restriction training and sport nutrition supplementation to augment functional capacity and increase muscle strength in twenty-four abdominal cancer patients awaiting surgery. MATERIALS AND METHODS: The sport science-based program was comprised of blood flow restriction exercise 5 to 6 times per week and a daily sports nutrition supplement containing l-citrulline, creatine monohydrate, and whey protein. RESULTS: After 4 weeks of prehabilitation, 6-min walk test, timed up and go, short physical performance battery, 5-chair stand test and physical component score of quality of life were significantly improved (all p < 0.05). Total body and appendicular lean mass as assessed by dual energy X-ray absorptiometry increased by 0.73 ± 1.04 kg (p = 0.004) and 0.42 ± 0.64 kg (p = 0.006), respectively. Total body fat mass and trunk fat mass decreased (p = 0.004 and p = 0.021). There were no significant changes in hand grip strength, fear of falling, the mental component summary of quality of life, or fasting serum concentrations of myostatin, follistatin, and growth hormone. CONCLUSION: A multimodal prehabilitation program, which encompasses blood flow restriction training and sports nutrition supplements, is both feasible and effective in improving lean mass and physical function in abdominal cancer patients prior to surgery.

Including Medical Management in the Urologic Approach to Idiopathic Retroperitoneal Fibrosis.

OBJECTIVE: To characterize the timing and effectiveness of medical management in resolving stent-dependent ureteral compression secondary to idiopathic retroperitoneal fibrosis (RPF), the long-term relevant outcomes, and the side effects of treatment. METHODS: A retrospective review of RPF patients diagnosed from 2002-2018 was performed. Patients with hydronephrosis due to ureteral involvement that were managed with medication and with temporary stenting as needed, but without initial ureterolysis, were included. Patient demographics and RPF management details were obtained, including the following subsequent events: ureterolysis, nephrectomy, recurrent upper tract obstruction, and medication side effects. RESULTS: Fifty-two patients met inclusion criteria. Resolution of ureteral obstruction with medical management and temporary renal drainage as needed occurred in 36 (69%) patients with a median stent duration of 16 months, and median clinical and radiographic follow up of 4.2 and 3.3 years, respectively. Recurrent obstruction after a stent-free period occurred in 9 (18%) patients. Ureterolysis was performed in 8 (15%) patients at a median of 2.2 years for medication intolerance, lack of radiographic response to medication, or persisting pain. Potential medication side effects occurred in 6 (12%) patients. CONCLUSIONS: Medical management supported successful resolution of ureteral obstruction in 69% of patients without the need for ureterolysis after temporary renal drainage using stents, with rare incidence of worsening renal dysfunction or medication side effect. To date, this is the largest reported series of systematically managed RPF patients with obstructive uropathy receiving initial medical therapy and serves to counsel patients and advise urologists and nephrologists of the expected course and advantages and disadvantages of medical versus surgical management.

The Enhanced Recovery After Surgery (ERAS) Elements that Most Greatly Impact Length of Stay and Readmission.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to decrease length of stay (LOS) and improve patient outcomes in a wide variety of surgical fields; however, barriers exist preventing the implementation of all elements. We hypothesize that a subset of ERAS elements are most influential on LOS and readmission following colorectal surgery. STUDY DESIGN: A retrospective review of 840 patients was performed and their compliance with 24 ERAS components evaluated. Two independent machine-learning statistical algorithms were employed to determine which subset of ERAS elements was most impactful on LOS <3 days and hospital readmission. RESULTS: Increasing compliance with ERAS elements had an inverse linear relationship with LOS. Open (vs minimally invasive) surgery was associated with increased LOS. Early mobilization and multimodal pain management are the elements most protective against increased LOS. Readmissions increase with the number of morphine milligram equivalents (MME)/day. The subset of patients who underwent minimally invasive procedures, had multimodal pain control, and less than 16 MME per day were least likely (23%) to have >3-day LOS. Those patients who underwent an open procedure with less than 15 ERAS elements completed were most likely (84%) to have >3-day LOS. CONCLUSION: While increasing compliance with ERAS protocols and minimally invasive procedures decrease LOS and readmission overall, a subset of components-multimodal pain control, limited opioid use, and early mobilization-was most associated with decreased LOS and readmission. This study provides guidance on which ERAS elements should be emphasized.

Biopsy Cell Cycle Proliferation Score Predicts Adverse Surgical Pathology in Localized Renal Cell Carcinoma.

Active surveillance (AS) is an accepted management strategy for some patients with renal cell carcinoma, but limited tools are available to identify optimal AS candidates. While renal mass biopsy provides diagnostic information, risk stratification based on biopsy is limited. In a retrospective, multi-institutional cohort that underwent renal mass biopsy followed by surgery, we assessed the ability of the cell cycle proliferation (CCP) score from clinical biopsy specimens to predict adverse surgical pathology (ie, grade 3-4, pT stage ≥3, metastasis at surgery, or papillary type II). Of 202 patients, 98 (49%) had adverse surgical pathology. When added to a baseline model including age, sex, race, lesion size, biopsy grade, and histology, CCP score was significantly associated with adverse pathology when modeled as a binary (odds ratio [OR]: 2.44 for CCP score >0, p = 0.02) and a continuous (OR: 1.72 per one unit increase, p = 0.04) variable. Discriminative performance measured by the area under the curve (AUC) improved from 0.73 in the baseline model to 0.75 and 0.76 in models including the CCP score. In the subgroup of patients with nephrectomy CCP score available (n = 67), the biopsy-based model outperformed the nephrectomy-based model (AUC 0.78 vs 0.75). These data support prospective assessment of biopsy CCP score to confirm clinical validity and assess potential utility in AS-eligible patients. PATIENT SUMMARY: In patients with localized renal cell carcinoma who underwent renal mass biopsy followed by surgery, the cell cycle proliferation score from clinical biopsy specimens could predict adverse surgical pathology.

Value-based care for the treatment and evaluation of benign prostatic hyperplasia: an analysis of a metropolitan service area claims database.

PURPOSE: With an aging population, cost containment and improved outcomes will be crucial for a sustainable healthcare ecosystem. Current data demonstrate great variation in payments for procedures and diagnostic workup of benign prostatic hyperplasia (BPH). To help determine the best financial value in BPH care, we sought to analyze the major drivers of total payments in BPH. MATERIALS AND METHODS: Commercial and Medicare claims from the Truven Health Analytics Markestscan® database for the Austin, Texas Metropolitan Service Area from 2012 to 2014 were queried for encounters with diagnosis and procedural codes related to BPH. Linear regression was utilized to assess factors related to BPH-related payments. Payments were then compared between surgical patients and patients managed with medication alone. RESULTS: Major drivers of total payments in BPH care were operative, namely transurethral resection of prostate (TURP) [$2778, 95% CI ($2385-$3171), p < 0.001) and photoselective vaporization (PVP) ($3315, 95% CI ($2781-$3849) p < 0.001). Most office procedures were also associated with significantly higher payments, including cystoscopy [$708, 95% CI ($417-$999), p < 0.001], uroflometry [$446, 95% CI ($225-668), p < 0.001], urinalysis [$167, 95% CI ($32-$302), p = 0.02], postvoid residual (PVR) [$245, 95% CI ($83-$407), p < 0.001], and urodynamics [$1251, 95% CI ($405-2097), p < 0.001]. Patients who had surgery had lower payments for their medications compared to patients who had no surgery [$120 (IQR: $0, $550) vs. $532 (IQR: $231, $1852), respectively, p < 0.001]. CONCLUSION: Surgery and office-based procedures are associated with increased payments for BPH treatment. Although payments for surgery were more in total, surgical patients paid significantly less for BPH medications.

Occupational traumatic injuries rarely affect genitourinary organs: a retrospective, comparative study.

PURPOSE: To determine the mechanisms of injury associated with occupational injuries (OI) to genitourinary (GU) organs and compare GU OIs with GU non-OIs. METHODS: A single institution, retrospective study was conducted at a level 1 trauma center between 2010 and 2016 of all patients with GU injuries. OI was defined as any traumatic event that occurred in the workplace requiring hospital admission. Types of occupations were recorded in addition to the location of injury, mechanisms of injury, concomitant injuries, operative interventions, total cost, and mortality. GU OI patients were then compared to GU non-OI patients. RESULTS: 623 patients suffered a GU injury, of which 39 (6.3%) had a GU OI. Fall (43%) was the most common mechanism of injury; followed by motor vehicle collision/motorcycle crash (31%), crush injury (18%), and pedestrian struck (8%). The adrenal gland (38%) and kidney (38%) were the most commonly injured organs. There was no difference in mortality (13% GU OI vs. 15% GU non-OI, p = 0.70) or total direct cost ($21,192 ± 28,543 GU OI vs. $28,215 ± 32,332 GU non-OI, p = 0.45). Total costs were decreased with mortality from a GU injury (odds ratio (OR) 0.3, CI 0.26-0.59; p = < 0.001) and increased with higher injury severity scores (OR 1.1, CI 1.09-1.2; p = < 0.0001). Total costs were not affected by OI status. CONCLUSIONS: Occupational GU trauma presents with similar patterns of injury, hospital course, and direct cost as GU trauma that occurs in non-occupational settings.

Enterorenal Fistula as an Unusual Complication from Ureteroscopic Lithotripsy: A Case Report.

Background: This case highlights an enterorenal fistula as a rare complication from ureteroscopic lithotripsy. Case Presentation: A 56-year-old woman with significant obesity, decompensated cirrhotic and ascitic liver disease, hypertension, type 2 diabetes mellitus, and nephrolithiasis treated with five prior ureteroscopic lithotripsies for a partial left staghorn stone presented to the emergency department (ED) with worsening left flank pain and sepsis. A CT scan of the abdomen and pelvis with contrast showed a large left perinephric hematoma. She underwent drain placement and during fluoroscopic imaging, there was a fistula from the left subcapsular hematoma/abscess to the proximal descending colon. The patient wished to proceed with a surgical course involving nephrectomy with hemicolectomy despite extensive counseling regarding her high mortality risk. However, because of worsening nutritional status as well as several other high-risk comorbidities, a shared decision was made with the patient to postpone the procedure. The patient was discharged to a skilled nursing facility for nutritional optimization and prehabilitation; however, she continued to decline with recurrent sepsis and cirrhosis-related complications and unfortunately passed away. Conclusion: A subscapular hematoma evolving into a perinephric abscess is a rare but known complication of ureteroscopic lithotripsy; however, this patient developed an enterorenal fistula that has yet to be reported after repeated ureteroscopy.

International and Multi-institutional Assessment of Factors Associated With Performance and Quality of Lymph Node Dissection During Radical Nephrectomy.

OBJECTIVE: To determine factors associated with performance and quality of lymph node dissection during radical nephrectomy. MATERIALS AND METHODS: Using an International Data Registry, we performed multilevel logistic regression to determine the association of surgical approach (open surgery vs minimally invasive surgery), institutional experience (low, moderate, and high tertiles), and institutional preference (minimally invasive surgery, balanced, and open surgery tertiles) with the performance of lymph node dissection in subgroups by clinical stage and nodal status. RESULTS: Among 1,742 patients undergoing radical nephrectomy, 312 (18%) underwent lymph node dissection, which was associated with stage (28% for ≥cT2 vs 9.3% for cT1), and nodal status (68% for ≥cN1 vs 13% for cN0). Open surgery was significantly associated with performing lymph node dissection in all subgroups. Institutional experience and institutional preference had no association with performing lymph node dissection in the ≥cN1 group. The number of nodes removed was greater for open surgery (mean 5.9) vs minimally invasive surgery (mean 3.4); this held true even when stratified by stage and nodal status. CONCLUSION: In this large dataset, open surgical radical nephrectomy is associated with more frequent performance and higher quality of lymph node dissection, which may owe to selection bias but also could reflect technical concerns. In the patient population in whom lymph node dissection is recommended (≥cN1), this is not explained by institutional experience or preference. Lymph node dissection may be under-utilized for ≥cN1 disease and over-utilized for cN0 disease, at least according to practice guidelines.

American Urological Association, American College of Emergency Physicians and American College of Radiology Quality Improvement Summit 2017: Challenges and Opportunities for Stewardship of Urological Imaging.

INTRODUCTION: Since 2014 the AUA (American Urological Association) has convened several Quality Improvement Summits to provide education and promote dialogue around issues of quality improvement and patient safety. The 2017 Summit, Challenges and Opportunities for Stewardship of Urological Imaging, organized in partnership with the American College of Radiology and the American College of Emergency Physicians, highlighted opportunities for collaborative improvement in the value, safety and quality of imaging for patients with urological conditions. METHODS: The Summit was held at AUA headquarters in Linthicum, Maryland on October 21, 2017. Each talk, panel and working group held during the summit highlighted gaps in care being addressed by physician led stewardship initiatives in imaging, in general, as well as multiple specific examples related to prostate cancer and urinary stone disease. RESULTS: Presentations facilitated information exchange on quality efforts between clinicians across disciplines and care settings and served to educate urology practitioners, primary care physicians, and specialists about existing patient centered quality improvement programs. CONCLUSIONS: This exchange serves to accelerate adoption of evidence-based practices and brings together stakeholder organizations to form partnerships that facilitate the further development of research and policy agendas to advance physician led stewardship of advanced imaging across emergency medicine, radiology and urology. In parallel, this meeting established a consortium to develop and disseminate tools for facilitating organizational improvement activities needed to enhance the quality and safety of medical care.

Current management of pelvic fracture urethral injuries: to realign or not?

The acute management of pelvic fracture urethral injuries (PFUIs) remains a controversial topic. Currently, suprapubic tube (SPT) placement with delayed repair or primary realignment (PR) represents the strategies used to treat patients. While many will advocate the use of one technique over the other, the 2014 American Urological Association (AUA) Guidelines give providers the option for the management PFUI. Current literature evaluates these two interventions, focusing on the incidence of re-stricture formation, erectile dysfunction, and urinary incontinence. Here we perform a comprehensive review of the current management for PFUI, as well as, discuss the limitations of the studies and need for more prospective studies on this debated topic.