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1.
Semin Vasc Surg ; 36(4): 560-570, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38030330

ABSTRACT

The goal of this systematic review was to collate and summarize the current literature on hemodialysis access outcomes in females, identify differences between females and men, and provide a foundation for future research. A systematic review of the English-language literature was conducted by searching PubMed and Google Scholar for the following terms: "sex," "hemodialysis access," "arteriovenous fistula," "arteriovenous graft," and "dialysis catheter." Reference lists from the resulting articles were also evaluated to ensure that any and all relevant primary sources were identified. Studies were then screened by two independent reviewers for inclusion. Of 967 total studies, 53 ultimately met inclusion criteria. Females have lower maturation rates; have decreased rates of primary, primary-assisted, and secondary patency; require more procedures per capita to achieve maturation and to maintain fistula patency; are more likely to receive dialysis via an arteriovenous graft or central venous catheter; and require a longer time and potentially more assistive invasive interventions to achieve a mature fistula. Our findings emphasize the urgent need for further research to evaluate and address the causes of these disparities. Discussion with patients undergoing hemodialysis should include these findings to improve patient education, expectations, satisfaction, and outcomes.


Subject(s)
Arteriovenous Shunt, Surgical , Central Venous Catheters , Fistula , Male , Female , Humans , Renal Dialysis/adverse effects , Renal Dialysis/methods , Arteriovenous Shunt, Surgical/adverse effects , Risk Factors , Retrospective Studies , Vascular Patency , Treatment Outcome
2.
Ann Vasc Surg ; 95: 197-202, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37270092

ABSTRACT

BACKGROUND: The end-stage kidney disease life-plan aims to individualize hemodialysis (HD) access selection in patients requiring renal replacement therapy. Paucity of data on risk factors for poor arteriovenous fistula (AVF) outcomes limits the ability of physicians to guide their patients on this decision. This is especially true for female patients, who are known to have worse AVF outcomes when compared to male patients. The goal of this study was to identify risk factors associated with poor AVF maturation outcomes in female patients that will help guide individualized access selection. METHODS: A retrospective review of 1,077 patients that had AVF creation between 2014 and 2021 at an academic medical center was performed. Maturation outcomes were compared between 596 male and 481 female patients. Separate multivariate logistic regression models were created for the male and female cohorts to identify factors associated with unassisted maturation. AVF was considered mature if it was successfully used for HD for 4-week sessions without need for further interventions. Unassisted fistula was defined as an AVF that matured without any interventions. RESULTS: The male patients were more likely to receive more distal HD access; 378 (63%) male versus 244 (51%) female patients had radiocephalic AVF, P < 0.001. Maturation outcomes were significantly worse in female patients; 387 (80%) AVFs matured in females and 519 (87%) in male patients, P < 0.001. Similarly, the rate of unassisted maturation was 26% (125) in female patients versus 39% (233) in male patients, P < 0.001. Mean preoperative vein diameters were similar in both groups; 2.8 ± 1.1 mm in male versus 2.7 ± 0.97 mm in female patients, P = 0.17. Multivariate logistic regression analysis of the female patients revealed that Black race (odds ratio [OR]: 0.6, 95% confidence interval [CI]: 0.4-0.9, P = 0.045), radiocephalic AVF (OR: 0.6, 95% CI: 0.4-0.9, P = 0.045), and preoperative vein diameter <2.5 mm (OR: 1.4, 95% CI: 10.33-0.901.1-1.7, P = 0.014) were independent predictors of poor unassisted maturation in this cohort. In male patients, preoperative vein diameter <2.5 mm (OR: 1.4, 95% CI: 1.2-1.7, P < 0.001) and need for HD prior to AVF creation (OR: 0.6, 95% CI: 0.3-0.9, P = 0.018) were independent predictors of poor unassisted maturation. CONCLUSIONS: Black women with marginal forearm veins may have worse maturation outcomes, and upper arm HD access should be considered when advising patients on their end-stage kidney disease life-plan.


Subject(s)
Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Kidney Failure, Chronic , Humans , Male , Female , Arteriovenous Shunt, Surgical/adverse effects , Treatment Outcome , Vascular Patency , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/etiology , Renal Dialysis , Retrospective Studies , Arteriovenous Fistula/etiology
3.
Ann Vasc Surg ; 95: 203-209, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37121342

ABSTRACT

BACKGROUND: Up to 60% of arteriovenous fistulas (AVF) require intervention to assist maturation, which prolongs the time until it can be used for hemodialysis (HD). Current guidelines recommend early postoperative AVF examination to detect and address immaturity to decrease time to maturation. This study evaluates how the timing of postoperative follow-up to assess AVF maturity affects patients' outcomes. METHODS: All patients who underwent AVF creation between 2017 and 2021 in an academic medical center were retrospectively reviewed, excluding patients lost to follow-up or not on HD. Outcomes were compared between patients that had delayed follow-up to assess AVF maturity, >8 weeks post surgery, versus early follow-up, <8 weeks post-surgery. AVF evaluation for maturity consisted of physical examination and duplex ultrasound. Primary endpoints were time to first cannulation (interval from AVF creation to first successful cannulation) and time to catheter-free dialysis (interval from AVF creation to central venous catheter removal). RESULTS: A total of 400 patients were identified: 111 in the delayed follow-up group and 289 in the early follow-up group. The median time to follow-up was 78 days (interquartile range [IQR], 66-125) in the delayed follow-up group versus 39 days (IQR, 36-47) in the early follow-up group, (P < 0.0001). The maturation rate was 87% in the delayed follow-up group versus 81% in the early follow-up group, (P = 0.1) and both groups had similar rates of interventions to assist maturation (66% vs. 57%, P = 0.2). The early follow-up group had a significantly shorter median time to first cannulation (50 vs. 88 days; P < 0.0001) and shorter time to catheter-free HD (75 vs. 118 days; P <0.0001). At 4 months after AVF creation, the incidence of first cannulation was 74% in the early follow-up group versus 63% in the delayed follow-up group (P = 0.001). Similarly, the incidence of catheter-free dialysis was 65% in the early follow-up group versus 50% in the delayed follow-up group at 4 months postoperatively, (P = 0.036). CONCLUSIONS: Early postoperative follow-up for evaluation of fistula maturation is associated with reduced time to first successful cannulation of AVF for HD and reduced time to catheter-free dialysis.


Subject(s)
Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Kidney Failure, Chronic , Humans , Follow-Up Studies , Retrospective Studies , Treatment Outcome , Renal Dialysis/adverse effects , Arteriovenous Fistula/etiology , Arteriovenous Shunt, Surgical/adverse effects , Vascular Patency , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/etiology
4.
J Vasc Surg Cases Innov Tech ; 9(2): 101133, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36970137

ABSTRACT

Balloon-assisted maturation (BAM) of arteriovenous fistulas has conventionally been performed via direct fistula access. The transradial approach has not been well described for BAM, although its use has been reported throughout the cardiology literature. The purpose of the present study was to assess the outcomes of transradial access for its use with BAM. A retrospective review of 205 patients with transradial access for BAM was performed. One sheath was inserted into the radial artery distal to the anastomosis. We have described the procedural details, complications, and outcomes. The procedure was considered technically successful if transradial access had been established and the AVF had been ballooned with at least one balloon without major complications. The procedure was considered clinically successful if no further interventions had been required for AVF maturation. The average time for BAM via transradial access was 35 ± 20 minutes, with 31 ± 17 mL of contrast used. No access-related perioperative complications, including access site hematoma, symptomatic radial artery occlusion, or fistula thrombosis, had occurred. The technical success rate was 100%, and the rate of clinical success was 78%, with 45 patients requiring additional procedures to achieve maturation. Transradial access is an efficient alternative to trans-fistula access for BAM. It is technically easier and allows for better visualization of the anastomosis.

5.
Am J Surg ; 225(1): 103-106, 2023 01.
Article in English | MEDLINE | ID: mdl-36208956

ABSTRACT

BACKGROUND: We assessed the utility of intraoperative vein mapping performed by the operating surgeon for evaluating vessel suitability for arteriovenous fistula (AVF) creation. METHODS: In a retrospective review of 222 AVFs, vein diameter measurements were compared between intraoperative and preoperative mapping in the same anatomical location. AVF creation was based on intraoperative vein diameter ≥2 mm, using a distal to proximal and superficial veins first approach. Potential selection of access type based on preoperative findings alone was analyzed. RESULTS: The mean diameter of the veins used for AVF creation measured 3.6 ± 0.8 mm on intraoperative duplex versus 2.5 ± 0.9 mm when the same veins were measured on preoperative duplex. Based on preoperative mapping alone, 23% of patients would have received a more proximal AVF and 5% would have needed a graft. AVFs created more distally based on intraoperative findings had similar maturation rates compared to the rest of the cohort, 79% versus 84% (p = 0.2). CONCLUSIONS: Intraoperative vein mapping can be used to evaluate vessel suitability for AVF and compared to pre-operative vein mapping may increase the eligibility of distal veins for fistula creation while reducing the need for AV grafts.


Subject(s)
Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Humans , Vascular Patency , Renal Dialysis , Veins/diagnostic imaging , Veins/surgery , Retrospective Studies , Arteriovenous Fistula/surgery , Treatment Outcome
6.
J Vasc Surg Venous Lymphat Disord ; 10(6): 1352-1358, 2022 11.
Article in English | MEDLINE | ID: mdl-35940449

ABSTRACT

OBJECTIVE: Extremity venous aneurysms result in the risk of pulmonary embolism (PE) and chronic venous insufficiency. At present, owing to the rarity of these aneurysms, no consensus for their treatment has been established. The purpose of the present study was to review the presentation, natural history, and contemporary management of extremity venous aneurysms. METHODS: We performed a retrospective, multi-institutional review of all patients with extremity venous aneurysms treated from 2008 to 2018. A venous aneurysm was defined as saccular or fusiform with an aneurysm/vein ratio of >1.5. RESULTS: A total of 66 extremity aneurysms from 11 institutions were analyzed, 40 of which were in a popliteal location, 14 iliofemoral, and 12 in an upper extremity or a jugular location. The median follow-up was 27 months (range, 0-120 months). Of the 40 popliteal venous aneurysms, 8 (20%) had presented with deep vein thrombosis (DVT) or PE, 13 (33%) had presented with pain, and 19 had been discovered incidentally. The mean size of the popliteal venous aneurysms presenting with DVT or PE was larger than that of those presenting without thromboembolism (3.8 cm vs 2.5 cm; P = .003). Saccular aneurysm morphology in the lower extremity was associated with thromboembolism (30% vs 9%; P = .046) and fusiform aneurysm morphology with a thrombus burden >25% (45% vs 3%). Patients presenting with thromboembolism were more likely to have had a thrombus burden >25% in their lower extremity venous aneurysm compared with those who had presented without thromboembolism (70% vs 9%). Approximately half of all the patients underwent immediate intervention, and half were managed with observation or antithrombotic regimen. In the non-operative cohort, three patients subsequently developed a DVT. Eight patients in the medically managed cohort went on to require surgical intervention. Of the 12 upper extremity venous aneurysms, none had presented with DVT or PE, and only 2 (17%) had presented with pain. Of the 66 patients in the entire cohort, 41 underwent surgical intervention. The most common indication was the absolute aneurysm size. Nine patients had undergone surgery because of a DVT or PE, and 11 for pain or extremity swelling. The most common surgery was aneurysmorrhaphy in 21 patients (53%), followed by excision and ligation in 14 patients (35%). Five patients (12%) had undergone interposition bypass grafting. A postoperative hematoma requiring reintervention was the most common complication, occurring in three popliteal vein repairs and one iliofemoral vein repair. None of the patients, treated either surgically or medically, had reported post-thrombotic complications during the follow-up period. CONCLUSIONS: Large lower extremity venous aneurysms and saccular aneurysms with thrombus >25% of the lumen are more likely to present with thromboembolic complications. Surgical intervention for lower extremity venous aneurysms is indicated to reduce the risk of venous thromboembolism (VTE) and the need for continued anticoagulation. Popliteal aneurysms >2.5 cm and all iliofemoral aneurysms should be considered for repair. Upper extremity aneurysms do not have a significant risk of VTE and warrant treatment primarily for symptoms other than VTE.


Subject(s)
Aneurysm , Pulmonary Embolism , Venous Thromboembolism , Aneurysm/diagnostic imaging , Aneurysm/surgery , Anticoagulants , Fibrinolytic Agents , Humans , Lower Extremity/blood supply , Pain , Popliteal Vein/diagnostic imaging , Popliteal Vein/surgery , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/etiology , Pulmonary Embolism/therapy , Retrospective Studies , Risk Factors , Venous Thromboembolism/complications
7.
J Vasc Surg Cases Innov Tech ; 8(1): 13-15, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35036666

ABSTRACT

A 72-year-old man had presented with a 4-day history of progressive left-sided facial swelling associated with pain. The physical examination revealed left facial fullness over the parotid gland without tenderness to palpation. His vital signs and laboratory test findings were within normal limits. A computed tomography scan demonstrated a left facial varix measuring 3.4 cm × 2.8 cm within an unremarkable-appearing parotid gland. Parotidectomy vs close observation were discussed, and the patient decided to pursue nonoperative management. Ultimately, his symptoms were self-limited, and the swelling had resolved within 6 months after the diagnosis. Interval computed tomography demonstrated a thrombosed left facial varix measuring 1.3 cm × 1.1 cm.

8.
EJVES Vasc Forum ; 53: 26-29, 2021.
Article in English | MEDLINE | ID: mdl-34849498

ABSTRACT

OBJECTIVE: Vascular access induced digital ischaemia is an uncommon complication of haemodialysis access procedures and is difficult to manage. Several techniques have been described to treat this phenomenon, with variable long term success. Although all of these procedures have been shown to work, they have a significant failure rate, such as persistent high vascular access flow or loss of access. One of the major technical limitations of these techniques is the lack of quantitative data gathered during the procedure to ensure treatment success. In this study, the aim was to describe a novel technique that can improve the success of banding in preserving access and eliminating digital ischaemia. TECHNIQUE: A modified method for arteriovenous fistula banding that incorporates measurements of distal arterial pressure to improve the success of the procedure is described. RESULTS: Sixteen patients with vascular access induced digital ischaemia and high-flow vascular access were treated using the technique. All procedures were technically successful. At 30 days, complete symptomatic relief (clinical success) was seen in 81% (n = 13) of patients. There was no access thrombosis or infection in any of the patients at the 30 day follow up. Six month follow up data were available in seven patients. There was no loss of access patency or recurrence of symptoms observed at six months. CONCLUSION: This novel technique is simple and effective and can be used safely as first line therapy for the management of vascular access induced digital ischaemia.

9.
J Cardiovasc Surg (Torino) ; 62(5): 413-419, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33881285

ABSTRACT

INTRODUCTION: The aim of this review article was to compare the outcomes of newer non-thermal endovenous ablation techniques to thermal ablation techniques for the treatment of symptomatic venous insufficiency. EVIDENCE ACQUISITION: Three independent reviewers screened PubMed and EMBASE databases to identify relevant studies. A total of 1173 articles were identified from database search that met our inclusion criteria. Two articles were identified through reference search. Removal of duplicates from our original search yielded 695 articles. We then screened these articles and assessed 173 full-text articles for eligibility. Subsequent to exclusion, 11 full-text articles were selected for final inclusion. EVIDENCE SYNTHESIS: The non-thermal techniques are similar to thermal techniques in terms of a high technical success rate, closure rate at 12 months, change in Venous Clinical Severity Score and change in quality of life after procedure. However, the length of procedure is shorter for non-thermal modalities and patient comfort is improved with lower pain scores. Return to work may also be earlier after non-thermal ablation. The rates of bruising, phlebitis and paresthesia are higher after thermal ablation. CONCLUSIONS: The non-thermal modalities are safe and effective in treating venous reflux and have shown improved patient comfort and shorter length of procedure which may make them favorable for use compared to the thermal modalities.


Subject(s)
Ablation Techniques , Endovascular Procedures , Venous Insufficiency/surgery , Ablation Techniques/adverse effects , Endovascular Procedures/adverse effects , Humans , Operative Time , Postoperative Complications/etiology , Quality of Life , Return to Work , Risk Factors , Time Factors , Treatment Outcome , Venous Insufficiency/diagnostic imaging , Venous Insufficiency/physiopathology
10.
Ann Vasc Surg ; 71: 208-214, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32890643

ABSTRACT

BACKGROUND: Traditional practice suggests the abandonment of veins smaller than 3 mm in diameter for arteriovenous fistula (AVF) creation because of a low rate of maturation. This study aims to show that with balloon-assisted maturation (BAM), undersized veins can be used to create functional AVFs with a high rate of success. METHODS: All patients who underwent AVF creation between 2014 and 2018 at a tertiary academic medical center were retrospectively reviewed. The patients without preoperative vein mapping, those who failed to follow-up, and the patients who were not on dialysis were excluded. A fistula was considered to be mature if it was successfully cannulated for dialysis. A total of 596 patients were identified for analysis. The cohort was divided into the small-vein group (SVG, <2.5 mm) and large-vein group (LVG, ≥2.5 mm) based on preoperative vein size. Categorical variables were analyzed with the chi-squared test for their association with maturation status. Continuous variables were analyzed with the Wilcoxon rank sum test. A P-value less than 0.05 was considered significant. RESULTS: In the study cohort, 61.9% of the patients were male, with an average age of 62.8 ± 13.7 years, and an average preoperative vein size of 2.9 ± 1.1 mm. With similar demographic distribution, the participants in the SVG (n = 216) had significantly smaller preoperative vein size of 1.9 ± 0.4 mm than the patients in the LVG (n = 380), 3.5 ± 0.8 mm (P = 0.001). There were significantly more radio-cephalic AVFs created in the SVG (77.8% versus 48.7%, P < 0.0001). The overall maturation rate was 83.1% (n = 495), 219 fistulas (36.7%) matured primarily and 276 (46.3%) required interventions. Ninety-one percent of the patients required only 1 or 2 BAMs to achieve maturation. The SVG achieved a maturation rate of 75.9% as compared with 87.1% in the LVG (P = 0.002). A significantly higher number of patients in the SVG required BAM for maturation as compared with the LVG (67.7% versus 49.9%, P = 0.0002); however, there was no difference in the average number of BAMs required for fistula maturation between the groups (1.5 ± 0.8 for the SVG vs. 1.4 ± 0.7 for the LVG). In multivariable logistic regression analysis, vein size ≥2.5 mm (odds ratio (OR) = 2.11, confidence interval (CI): 1.36-3.27, P = 0.0009) and male sex (OR = 2.30, CI: 1.49-3.57, P = 0.0002) were independent predictors of maturation. CONCLUSIONS: Small veins can be used for AVF creation with lower but still favorable maturation rates using BAM interventions, especially in male patients. This practice can increase the creation of autogenous dialysis access and potentially reduce complications related to prosthetic dialysis access.


Subject(s)
Arteriovenous Shunt, Surgical , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Renal Dialysis , Upper Extremity/blood supply , Veins/surgery , Aged , Arteriovenous Shunt, Surgical/adverse effects , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Databases, Factual , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome , Vascular Patency , Veins/diagnostic imaging
11.
Ann Vasc Surg ; 70: 290-294, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32866580

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) predisposes to arterial and venous thromboembolic complications. We describe the clinical presentation, management, and outcomes of acute arterial ischemia and concomitant infection at the epicenter of cases in the United States. METHODS: Patients with confirmed COVID-19 infection between March 1, 2020 and May 15, 2020 with an acute arterial thromboembolic event were reviewed. Data collected included demographics, anatomical location of the thromboembolism, treatments, and outcomes. RESULTS: Over the 11-week period, the Northwell Health System cared for 12,630 hospitalized patients with COVID-19. A total of 49 patients with arterial thromboembolism and confirmed COVID-19 were identified. The median age was 67 years (58-75) and 37 (76%) were men. The most common preexisting conditions were hypertension (53%) and diabetes (35%). The median D-dimer level was 2,673 ng/mL (723-7,139). The distribution of thromboembolic events included upper 7 (14%) and lower 35 (71%) extremity ischemia, bowel ischemia 2 (4%), and cerebral ischemia 5 (10%). Six patients (12%) had thrombus in multiple locations. Concomitant deep vein thrombosis was found in 8 patients (16%). Twenty-two (45%) patients presented with signs of acute arterial ischemia and were subsequently diagnosed with COVID-19. The remaining 27 (55%) developed ischemia during hospitalization. Revascularization was performed in 13 (27%) patients, primary amputation in 5 (10%), administration of systemic tissue- plasminogen activator in 3 (6%), and 28 (57%) were treated with systemic anticoagulation only. The rate of limb loss was 18%. Twenty-one patients (46%) died in the hospital. Twenty-five (51%) were successfully discharged, and 3 patients are still in the hospital. CONCLUSIONS: While the mechanism of thromboembolic events in patients with COVID-19 remains unclear, the occurrence of such complication is associated with acute arterial ischemia which results in a high limb loss and mortality.


Subject(s)
Arterial Occlusive Diseases/epidemiology , COVID-19/epidemiology , Thromboembolism/epidemiology , Acute Disease , Aged , Amputation, Surgical , Anticoagulants/therapeutic use , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/mortality , Arterial Occlusive Diseases/therapy , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Databases, Factual , Female , Hospital Mortality , Humans , Incidence , Male , Middle Aged , New York City/epidemiology , Retrospective Studies , Thromboembolism/diagnostic imaging , Thromboembolism/mortality , Thromboembolism/therapy , Thrombolytic Therapy , Treatment Outcome , Vascular Surgical Procedures
12.
J Gastrointest Oncol ; 6(2): 165-71, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25830036

ABSTRACT

BACKGROUND: Epidemiologic studies suggest that lower bone mineral density (BMD) is associated with an increased risk for colorectal adenoma/cancer, especially in postmenopausal women. The aim of this study is to investigate the association between osteopenia and/or osteoporosis and colorectal adenomas in patients from a New York community hospital. METHODS: We performed a cross-sectional observational study on 200 patients who underwent screening colonoscopies and bone density scan (dual-energy X-ray absorptiometry) at Nassau University Medical Center from November 2009 to March 2011. Among these, 83 patients were identified as osteoporosis (T score of -2.5 or below) and 67 were osteopenia (T score between -1.0 and -2.5). Logistic regression model was performed to assess the association between osteopenia and/or osteoporosis and colorectal adenomas. RESULTS: Among the patients with osteopenia and osteoporosis, the mean ages were 59.1 years [standard deviation (SD) =8.9] and 61.5 (SD =8.9), respectively. There were 94.0%, 85.1% and 74.7% women, respectively, in normal BMD, osteopenia and osteoporosis groups. The prevalence of colorectal adenomas was 17.9% and 25.3% in the osteopenia and osteoporosis groups, respectively, and 18.0% in the normal BMD group. After adjustment for potential confounders including age, sex, race, body mass index (BMI), tobacco use, alcohol use, history of diabetes, hypertension, or dyslipidemia, osteoporosis was found to be associated with presence of colorectal adenomas more than 2, compared to the normal BMD group. No significant associations were found for the prevalence, size, and location of adenomas. CONCLUSIONS: Our study suggests that osteoporosis is significantly associated with the presence of multiple colorectal adenomas. Prospective studies with a larger sample size are warranted in the future.

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