Cervical Health in Systemic Lupus Erythematosus.

Objective: A health disparity exists for African American (AA) women with systemic lupus erythematosus (SLE) who have increased prevalence of human papilloma virus (HPV) infection and cervical neoplasia. We used a self-sampling brush to obtain cervical cells to assess cytology, HPV infection, and vaginal cytokine production in AA women with SLE. Methods: Thirty AA women with SLE ages 18-50 years consented to participate. Clinical information was obtained by review of records and patient interviews, and surveys administered to assess cervical health history, knowledge of HPV, and satisfaction with the self-sampling brush. Vaginal samples were analyzed for cytology, HPV DNA and RNA, and vaginal cytokine RNA. Results: Our cohort (mean 36.9, ±9.4 years) had moderate/severe SLE and were on immunosuppressives. The majority had history of abnormal pap smears (63%) with prevalent risk factors for HPV infection: multiple sex partners (9.5 ± 7), not vaccinated for HPV (83.3%), smoking (26.7%), and not using condoms (73.3%). Most were aware of HPV causing cervical cancer (70%) but were unaware of other HPV-related diseases. Most preferred self-sampling over traditional pap smear (80%). Abnormal cytology was detected in 13.3%. HPV DNA was detected in 70%, with half showing multiple types, and all showing active infection (+RNA). HPV-infected samples demonstrated RNA expression of multiple cytokines with no specific/ consistent pattern. Conclusion: Our high-risk cohort lacked knowledge about HPV-related diseases and were not employing strategies to reduce their risk with vaccination and condoms. This study highlights the need for cervical health education, increased monitoring, and intervention in these high-risk women.

Detection of atrial fibrillation by implantable loop recorders following cryptogenic stroke: A retrospective study of predictive factors and outcomes.

PURPOSE: Cryptogenic strokes account for 40% of ischemic strokes. Atrial fibrillation (AF) is a known cause of stroke. Current data shows that occult AF is detected by implantable devices at higher rates than conventional monitoring. The objective of this study was to investigate risk factors and outcomes associated with AF detection by implantable loop recorders (ILRs) in patients with cryptogenic stroke. METHODS: We conducted a retrospective study of 172 patients admitted with cryptogenic stroke at Ascension St John and Macomb-Oakland Hospitals who had ILRs placed from 1/1/2016 to 1/31/2020. AF detection was defined as sustained AF for 30 s. RESULTS: The incidence of AF detection by ILR was 14% (24/172) over a mean follow-up of 12.75 ± 10.71 months. The mean duration of monitoring prior to AF detection was 4.5 months. The median duration of AF was 6 min. With univariable analysis, older age (p = 0.03), male sex (p = 0.09), embolic stroke pattern on imaging (p = 0.06), and presence of symptoms (p = 0.001) were associated with AF detection. Using multivariable analysis, patients with AF were more likely to be older (OR = 1.04, p = 0.04), male (OR = 3.6, p = 0.03), symptomatic (OR = 6.3, p = 0.01), and had embolic stroke pattern (OR = 3.3, p = 0.04). 95.8% of patients with AF were started on anticoagulation for secondary stroke prevention. CONCLUSION: In patients with cryptogenic stroke, age, sex, stroke pattern, and presence of AF symptoms are independent predictors of AF detection by ILR. Most patients with AF were started on anticoagulation for secondary stroke prevention.

Coronavirus disease 2019 (COVID-19) and the risk of hypertensive disorders of pregnancy: a retrospective cohort study.

Objective: To evaluate of COVID-19 disease in pregnant women and its association with hypertensive disorders of pregnancy.Design: Retrospective Cohort StudySetting: Multicenter study from a large metropolitan hospital systemMethods: Patients who tested positive for COVID-19 during their pregnancy and delivered were compared to the three subsequent deliveries of patients who tested negative (controls). We evaluated the impact of COVID-19 on the development of hypertensive disorders of pregnancy.Results: Compared with pregnancies negative for SARs-CoV-2 infection, maternal SARs-CoV-2 infection was associated with an increased risk for hypertensive disorders of pregnancy (OR 3.68, 95% CI 1.67 - 8.10).Tweetable AbstractPatients who test positive for COVID-19 during their pregnancy are at increased risk of developing a hypertensive disorder of pregnancy. Earlier SARs-CoV-2 infection results in an increased risk of developing a hypertensive disorder.

Clinical Features and Risk Factors for In-Hospital Mortality From COVID-19 Infection at a Tertiary Care Medical Center, at the Onset of the US COVID-19 Pandemic.

BACKGROUND: Mortality from COVID-19 has been associated with older age, black race, and comorbidities including obesity, Understanding the clinical risk factors and laboratory biomarkers associated with severe and fatal COVID-19 will allow early interventions to help mitigate adverse outcomes. Our study identified risk factors for in-hospital mortality among patients with COVID-19 infection at a tertiary care center, in Detroit, Michigan. METHODS: We conducted a single-center, retrospective cohort study at a 776-bed tertiary care urban academic medical center. Adult inpatients with confirmed COVID-19 (nasopharyngeal swab testing positive by real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay) from March 8, 2020, to June 14, 2020, were included. Clinical information including the presence of comorbid conditions (according to the Charlson Weighted Index of Comorbidity (CWIC)), initial vital signs, admission laboratory markers and management data were collected. The primary outcome was in-hospital mortality. RESULTS: Among 565 hospitalized patients, 172 patients died for a case fatality rate of 30.4%. The mean (SD) age of the cohort was 64.4 (16.2) years, and 294 (52.0%) were male. The patients who died were significantly older (mean [SD] age, 70.4 [14.1] years vs 61.7 [16.1] years; P < 0.0001), more likely to have congestive heart failure (35 [20.3%] vs 47 [12.0%]; P = 0.009), dementia (47 [27.3%] vs 48 [12.2%]; P < 0.0001), hemiplegia (18 [10.5%] vs 18 [4.8%]; P = 0.01) and a diagnosis of malignancy (16 [9.3%] vs 18 [4.6%]; P = 0.03).From multivariable analysis, factors associated with an increased odds of death were age greater than 60 years (OR = 2.2, P = 0.003), CWIC score (OR = 1.1, P = 0.023), qSOFA (OR = 1.7, P < 0.0001), WBC counts (OR = 1.1, P = 0.002), lymphocytopenia (OR = 2.0, P = 0.003), thrombocytopenia (OR = 1.9, P = 0.019), albumin (OR = 0.6, P = 0.014), and AST levels (OR = 2.0, P = 0.004) on admission. CONCLUSIONS: This study identified risk factor for in-hospital mortality among patients admitted with COVID-19 in a tertiary care hospital at the onset of U.S. Covid-19 pandemic. After adjusting for age, CWIC score, and laboratory data, qSOFA remained an independent predictor of mortality. Knowing these risk factors may help identify patients who would benefit from close observations and early interventions.

Do risk factors at the time of hospital admission differ by sex for in-hospital mortality from coronavirus disease 2019 (COVID-19)?

Background: Sex-disaggregated data for coronavirus disease 2019 (COVID-19) reported higher hospitalized fatality rates among men than women. Objective: To determine whether the risk factors for in-hospital mortality from COVID-19, present at the time of hospital admission, differed by patient sex. Design and setting: Single-center, retrospective cohort study at a tertiary-care urban academic center. Methods: We reviewed the electronic medical records of patients positive for COVID-19 via qualitative polymerase chain reaction (PCR) assay, admitted between March 8 and June 14, 2020. Patients were stratified by sex to assess the association of variables present on admission with in-hospital mortality. Results: The overall inpatient case fatality rate (CFR) was 30.4% (172 of 565). The CFR among male patients was higher than among female patients: 99 (33.7%) versus 73 (26.9%), respectively (P = .08). Among males, comorbid conditions associated with in-hospital mortality were chronic pulmonary disease (P = .02) and connective tissue disease (P = .03). Among females, these comorbid conditions were congestive heart failure (P = .03), diabetes with complication (P = .05), and hemiplegia (P = .02). Variables that remained independently associated with death in males included age >70 years, public insurance, incremental increase in quick sepsis-related organ failure assessment (qSOFA) and C-reactive protein (CRP), lymphocytopenia, and thrombocytopenia. Among females, variables that remained independently associated with mortality included public insurance, incremental increase in Charlson weighted index of comorbidity (CWIC) score, qSOFA, and CRP. Conclusions: Risk factors for in-hospital mortality by sex included public insurance type, incremental increase in qSOFA and CRP in both sexes. For male patients, older age, lymphocytopenia and thrombocytopenia were also associated with mortality, whereas a higher Charlson score was associated with in-hospital mortality in female patients.

Risk Factors for In-hospital Mortality from Coronavirus Disease 2019 Infection Among Black Patients-An Urban Center Experience.

BACKGROUND: Racial disparities are central in the national conversation about coronavirus disease 2019 (COVID-19) , with Black/African Americans being disproportionately affected. We assessed risk factors for death from COVID-19 among Black inpatients at an urban hospital in Detroit, Michigan. METHODS: This was a retrospective, single-center cohort study. We reviewed the electronic medical records of patients positive for severe acute respiratory syndrome coronavirus 2 (the COVID-19 virus) on qualitative polymerase chain reaction assay who were admitted between 8 March 2020 and 6 May 2020. The primary outcome was in-hospital mortality. RESULTS: The case fatality rate was 29.1% (122/419). The mean duration of symptoms prior to hospitalization was 5.3 (3.9) days. The incidence of altered mental status on presentation was higher among patients who died than those who survived, 43% vs 20.0%, respectively (P < .0001). From multivariable analysis, the odds of death increased with age (≥60 years), admission from a nursing facility, Charlson score, altered mental status, higher C-reactive protein on admission, need for mechanical ventilation, presence of shock, and acute respiratory distress syndrome. CONCLUSIONS: These demographic, clinical, and laboratory factors may help healthcare providers identify Black patients at highest risk for severe COVID-19-associated outcomes. Early and aggressive interventions among this at-risk population may help mitigate adverse outcomes.

Differences in Baseline Characteristics and Outcomes in Young Caucasians and African Americans with Acute Myocardial Infarction.

BACKGROUND: The incidence of acute myocardial infarction (AMI) in young patients is increasing. While race-related differences in clinical characteristics and outcomes for older AMI patients have been well-studied, such differences in young patients are unknown. METHODS: We performed a retrospective review of charts of Caucasian and African American (AA) patients <50 years of age, presenting with AMI between 2010 and 2017 in an urban, community hospital in Detroit, Michigan. RESULTS: A total of 271 patients were identified with 156 being AAs (57.5%). Mean age was 43 years which was similar in both groups. AAs with AMI were 2.2 times more likely to be women and to have a history of diabetes and 1.2 times more likely to have BMI >30 kg/m2. History of coronary artery disease (1.8-fold) and hypertension (1.5-fold) were also more common in AAs. Overall presenting features were similar, other than that AAs presented more often with non-ST-elevation MI and tended to present less often with cardiac arrest. No differences were observed in the angiographic findings or in-hospital outcomes in the two groups, with the exception of lower need of mechanical support in AAs. CONCLUSIONS: In conclusion, our data provide important, not previously described information on race-related differences in history, presentation, clinical and angiographic features and outcomes in AAs compared with Caucasians younger than 50 with AMI. These findings may have implications for tailoring specific preventive strategies to decrease the incidence of AMI and its associated adverse events in both racial groups.

Predictors for Severe COVID-19 Infection.

BACKGROUND: COVID-19 is a pandemic disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Predictors for severe COVID-19 infection have not been well defined. Determination of risk factors for severe infection would enable identifying patients who may benefit from aggressive supportive care and early intervention. METHODS: We conducted a retrospective observational study of 197 patients with confirmed COVID-19 admitted to a tertiary academic medical center. RESULTS: Of 197 hospitalized patients, the mean (SD) age of the cohort was 60.6 (16.2) years, 103 (52.3%) were male, and 156 (82.1%) were black. Severe COVID-19 infection was noted in 74 (37.6%) patients, requiring intubation. Patients aged above 60 were significantly more likely to have severe infection. Patients with severe infection were significantly more likely to have diabetes, renal disease, and chronic pulmonary disease and had significantly higher white blood cell counts, lower lymphocyte counts, and increased C-reactive protein (CRP) than patients with nonsevere infection. In multivariable logistic regression analysis, risk factors for severe infection included pre-existing renal disease (odds ratio [OR], 7.4; 95% CI, 2.5-22.0), oxygen requirement at hospitalization (OR, 2.9; 95% CI, 1.3-6.7), acute renal injury (OR, 2.7; 95% CI, 1.3-5.6), and CRP on admission (OR, 1.006; 95% CI, 1.001-1.01). Race, age, and socioeconomic status were not independent predictors. CONCLUSIONS: Acute or pre-existing renal disease, supplemental oxygen upon hospitalization, and admission CRP were independent predictors for the development of severe COVID-19. Every 1-unit increase in CRP increased the risk of severe disease by 0.06%.

Role of "Second Look" Lymph Node Search in Harvesting Optimal Number of Lymph Nodes for Staging of Colorectal Carcinoma.

As with other malignancies, lymph node metastasis is an important staging element and prognostic factor in colorectal carcinomas. The number of involved lymph nodes is directly related to decreased 5-year overall survival for all pT stages according to United States Surveillance, Epidemiology, and End Results (SEER) cancer registry database. The National Quality Forum specifies that the presence of at least 12 lymph nodes in a surgical resection is one of the key quality measures for the evaluation of colorectal cancer. Therefore, the harvesting of a minimum of twelve lymph nodes is the most widely accepted standard for evaluating colorectal cancer. Since this is an accepted quality standard, a second attempt at lymph node dissection in the gross specimen is often performed when the initial lymph node count is less than 12, incurring a delay in reporting and additional expense. However, this is an arbitrary number and not based on any hard scientific evidence. We decided to investigate whether the additional effort and expense of submitting additional lymph nodes had any effect on pathologic lymph node staging (pN). We identified a total of 99 colectomies for colorectal cancer in which the prosector subsequently submitted additional lymph nodes following initial review. The mean lymph node count increased from 8.3 ± 7.5 on initial search to 14.6 ± 8.0 following submission of additional sections. The number of cases meeting the target of 12 lymph nodes increased from 14 to 69. Examination of the additional lymph nodes resulted in pathologic upstaging (pN) of five cases. Gross reexamination and submission of additional lymph nodes may provide more accurate staging in a limited number of cases. Whether exhaustive submission of mesenteric fat or fat-clearing methods is justified will need to be further investigated.

Utility of Additional Tissue Sections in Surgical Pathology.

BACKGROUND: To avoid diagnostic errors such as missed diagnosis and errors in staging tumors due to inadequate tissue sampling, pathologists submit additional sections (AS). OBJECTIVE: This study assessed frequency, diagnostic yield, distribution, and cost of AS. METHOD: Among 1542 AS cases, we calculated mean AS per case; fraction of AS that altered diagnosis or stage; AS variation by tissue, malignant versus benign lesions, presence or absence of neoadjuvant therapy, mass, margin, lymph nodes, or other source, resident versus pathologist assistant (PA) dissector; and AS cost per case. RESULTS: Overall 9.2 ± 8.8 AS were collected per case. In only 3.8% (58/1542) of cases AS altered diagnosis or stage. Urinary bladder cases provoked the most AS: 19.5 ± 15.1 per case. Significantly more AS came from malignant versus benign lesions (10.8 ± 9.7 vs 7.6 ± 7.5, P = <.0001) and from specimens treated with neoadjuvant therapy versus malignant lesions not so treated (12.3 ± 9.4 vs 10.3 ± 9.8, P = .02). Lymph nodes were sampled more heavily compared with mass, margin, and other sites combined (11.8 ± 11.4 vs 8.9 ± 8.4, P = .003), but in 78.4% (1209/1542) of cases, AS were from mass. Of diagnosis or stage altering AS cases, two thirds (38/58) were from masses, one fifth (11/58) from lymph nodes, a 10th (6/58) from margins, and a 20th (3/58) from other specimen sites. Resident versus pathologist assistant dissection caused no significant AS difference. AS contributed 40% cost per case. CONCLUSIONS: AS per case ranged widely; their diagnostic yield was low; they were highest in urinary bladder specimens, in malignant and particularly neoadjuvant-treated lesions. Although lymph nodes were most heavily sampled, most AS were from masses. Resident dissection did not increase AS and cost of AS was high.

Patient Knowledge of Sunscreen Guidelines and Frequency of Physician Counseling: A Cross-sectional Study.

Background: Skin cancer and photodamage are problems commonly addressed by dermatologists. Despite the opportunities for chemoprevention with broad-spectrum sunscreen, there is little research investigating patient knowledge of proper sunscreen guidelines, or patient perception of physician counseling. Objective: The author sought to determine patient knowledge of the American Academy of Dermatology guidelines for proper sunscreen use and to obtain patient-reported rates of physician counseling regarding sunscreen. Design: We used a 12-question, multiple choice, anonymous survey to collect data. Setting: The study setting was a private dermatology clinic near Detroit, Michigan. PARTICIPANTS: Two hundred ninety- four adult patients presenting for routine office visits were included in the study. Results: About 59 percent of the subjects selected the recommended frequency of proper sunscreen use and 60 percent selected the recommended minimum sun protection factor. The minimum amount of sunscreen to cover the body, time of application before sun exposure, and time between reapplications of sunscreen did not receive a majority response. Differences in knowledge were seen between the sexes and skin types. Forty-four percent of patients previously received sunscreen counseling. Patients older than 40 years of age (39.3% vs. 18.4%, p=0.04), those who were fair skinned (62.5% vs. 23.8%), established patients (40.7% vs. 8.3%, p <0.0001), and those with a skin cancer (58.3% vs. 28%, p<0.0001) were more likely to report previous counseling. Conclusions: The majority of the study subjects never received counseling and lacked adequate knowledge of sunscreen guidelines. In order to obtain adequate primary prevention of skin cancer, it is essential to provide patients with further counseling and education on proper sunscreen use.

The incidence of cholelithiasis after sleeve gastrectomy and its association with weight loss: A two-centre retrospective cohort study.

INTRODUCTION: Gallstones commonly develop after Roux-en-Y gastric bypass and other bariatric surgery; however, incidence of gallstone development after SG has not been adequately studied. METHODS: We conducted a retrospective cohort study of patients who underwent SG at two institutions from January 1, 2011 to December 31, 2012. Patients with previous cholecystectomy, preexisting gallstones, gallbladder polyps, or the absence of preoperative abdominal imaging were excluded. Follow-up abdominal ultrasonography was performed once the patients achieved 80-lb weight loss, became symptomatic, or reached one-year post-surgery. The incidence of gallstones and symptomatic gallstones and/or bile sludge was calculated. Different parameters of early and late postoperative weight loss were compared between the patients who developed gallstones and those who did not. RESULTS: During the study period, 253 underwent laparoscopic sleeve gastrectomy. Ultimately, 96 patients met inclusion criteria and were evaluated. The incidence of gallstone formation was 47.9% (46/96), and the incidence of symptomatic gallstones was 22.9% (22/96). None of the weight loss parameters during the early and late postoperative period were significantly different between the patients who developed gallstones and those who did not. CONCLUSION: Gallstones are a common complication after rapid weight loss from SG. Our data suggest that gallstone formation during the weight loss period is not associated with amount or rate of weight loss both during the early or late postoperative period.

Can morbidly obese patients with reflux be offered laparoscopic sleeve gastrectomy? A case report of 40 patients.

BACKGROUND: The incidence of reflux in obesity can reach greater than 35%. Most surgeons recommend Roux-en-y gastric bypass to patients with pre-existing reflux. One alternative to Roux-en-y gastric bypass is the addition of anterior fundoplication (AF) with posterior crural approximation (pCA) to laparoscopic sleeve gastrectomy (LSG) in patients with documented reflux. METHODS: Between February 2011 and April 2013 we reviewed data from the bariatric registry on weight loss, resolution of symptoms, and quality of life presurgery and postsurgery for all patients who consented to participate in the registry and underwent LSG with AF/pCA. RESULTS: Forty patients met inclusion criteria; 78% (31) were female. The mean initial weight was 298 ± 64 lbs. with mean BMI of 49 ± 8 kg/m(2). The mean DeMeester score was 36 ± 27 (normal <14.7). Nine (22.5%) patients had esophagitis. Thirty-six (90%) patients had hiatal hernia. There were no intraoperative complications. The mean operative time was 84 ± 20 minutes and the mean hospital stay was 1.6 ± .9 days. Postoperative complications included 1 fluid collection, 1 narrowing, 4 admissions for nausea and dehydration, 1 for pancreatitis, and 1 for deep vein thrombosis . Thirty-eight (95%) patients had immediate resolution of reflux, whereas 2 (5%) patients complained of worsening symptoms. On short-term follow-up of 24 ± 6 months, 55% of patients responded to the gastroesophageal reflux disease-health related quality of life questionnaire with improvement in their median score from 31/75 interquartile range (IQR 25) preoperatively to 0/75 (IQR 6.5) postoperatively (P < .0001). Their %excess body mass index loss was 69 ± 27%. CONCLUSIONS: Morbidly obese patients with documented reflux can be offered LSG with the addition of AF/pCA.

Avoiding potential harm by improving appropriateness of urinary catheter use in 18 emergency departments.

STUDY OBJECTIVE: Urinary catheters are often placed in the emergency department (ED) and are associated with an increased safety risk for hospitalized patients. We evaluate the effect of an intervention to reduce unnecessary placement of urinary catheters in the ED. METHODS: Eighteen EDs from 1 health system underwent the intervention and established institutional guidelines for urinary catheter placement, provided education, and identified physician and nurse champions to lead the work. The project included baseline (7 days), implementation (14 days), and postimplementation (6 months, data sampled 1 day per month). Changes in urinary catheter use, indications for use, and presence of physician order were evaluated, comparing the 3 periods. RESULTS: Sampled patients (13,215) admitted through the ED were evaluated, with 891 (6.7%; 95% confidence interval [CI] 6.3% to 7.2%) having a catheter placed. Newly placed catheters decreased from 309 of 3,381 (9.1%) baseline compared with 424 of 6,896 (6.1%) implementation (Δ 3.0%; 95% CI 1.9% to 4.1%), and 158 of 2,938 (5.4%) postimplementation periods (Δ 3.8%; 95% CI 2.5% to 5.0%). The appropriateness of newly placed urinary catheters improved from baseline (228/308; 74%) compared with implementation (385/421; 91.4%; Δ 17.4%; 95% CI 11.9% to 23.1%) and postimplementation periods (145/158; 91.8%; Δ 23.9%; 95% CI 18% to 29.3%). Physician order documentation in the presence of the urinary catheter was 785 of 889 (88.3%), with no visible change over time. Improvements were noted for different-size hospitals and were more pronounced for hospitals with higher urinary catheter placement baseline. CONCLUSION: The implementation of institutional guidelines for urinary catheter placement in the ED, coupled with the support of clearly identified physician and nurse champions, is associated with a reduction in unnecessary urinary catheter placement. The effort has a substantial potential of reducing patient harm hospital-wide.

Laser in infra-popliteal and popliteal stenosis (LIPS): retrospective review of laser-assisted balloon angioplasty versus balloon angioplasty alone for below knee peripheral arterial disease.

Despite the use of laser technology over the last decade, there are limited data to show its procedural and clinical success in infra-popliteal disease. We hypothesized that laser-assisted balloon angioplasty (LABA) is at least similar or better in procedural and peri-procedural outcomes compared to balloon angioplasty (BA) alone, despite adverse lesion characteristics prior to intervention. Retrospective chart and angiogram review of consecutive critical limb ischemia (CLI) patients who underwent endovascular revascularization in the popliteal or infra-popliteal vessels between 2007 and 2012 with LABA or BA alone. Data from 731 patients revealed that baseline demographics were similar in the LABA (n = 398) and BA group (n = 333) with minor exceptions. More patients in the LABA group had TASC-D lesions (92.5 vs. 66.7 %; P < 0.0001) and chronic total occlusions (CTOs) in both vessel 1 (86.4 vs. 49.5 %; P < 0.0001) and vessel 2 (78.6 vs. 47.8 %; P < 0.0001). Multivariate analysis performed using logistic regression after adjusting for confounding factors showed use of LABA was associated with a 7 times greater likelihood of achieving <50 % residual disease compared to BA alone (OR 7.59, P < 0.0001), and a 5 times greater likelihood of improvement in the infra-popliteal lesion severity score than balloon angioplasty alone (OR 4.77, p < 0.0001). LABA is significantly better at achieving angiographic success and improving lesion severity score in spite of adverse lesion characteristics (more TASC-D lesions and CTOs) compared with BA alone. Our findings suggest that the use of LABA is an endovascular approach that is at least as effective and safe or better compared to BA for the treatment of CLI from complex popliteal and infra-popliteal vascular disease.