Improved long-term functional outcomes and mortality of patients with vascular-related amputations utilizing the lower extremity amputation pathway.

BACKGROUND: Enhanced recovery after surgery pathways lead to improve perioperative outcomes for patients with vascular-related amputations; however, long-term data and functional outcomes are lacking. This study evaluated patients treated by the lower extremity amputation pathway (LEAP) and identified predictors of ambulation. METHODS: A retrospective review of LEAP patients who underwent major amputation from 2016 to 2022 for Wound, Ischemia, and foot Infection stage V disease was performed. LEAP patients were matched 1:1 with retrospective controls (NOLEAP) by hospital, need for guillotine amputation, and final amputation type (above knee vs below knee). The primary end point was the Medicare Functional Classification Level (K level) (functional classification of patients with amputations) at the last follow-up. RESULTS: We included 126 patients with vascular-related amputations (63 LEAP and 63 NOLEAP). Seventy-one percent of the patients were male and 49% were Hispanic with a mean state Area Deprivation Index of 9/10. There were no differences in baseline demographics or comorbidities. All patients had a K level of >0 (ambulatory) before amputation and an average Modified Frailty Index of 4. The median follow-up was 270 days (interquartile range, 84-1234 days) in the NOLEAP group and 369 days (interquartile range, 145-481 days) in the LEAP group. Compared with NOLEAP patients, LEAP patients were more likely to receive a prosthesis (86% vs 44%;P > .001). LEAP patients were more likely to have a K level of >0 (60% vs 25%; P = .003). On multivariable logistic regression, participation in LEAP increased the odds of a K level of >0 at follow-up by 5.8-fold (odds ratio, 5.8; 95% confidence interval, 2.5-13.6). Patients with a K level of >0 had significantly higher survival at 4 years (93% vs 59%; P = .001). In a Cox proportional hazards model, adjusted for demographics, comorbidities and amputation level, a K level of >0 at follow-up was associated with an 88% decrease in the risk of mortality compared with a K level of 0. CONCLUSIONS: LEAP leads to improved ambulation with a prosthesis in a socioeconomically disadvantaged and frail patient population. Patients with a K level of >0 (ambulatory) have significantly improved mortality.

Community-wide feasibility of the Lower Extremity Amputation Protocol amongst vascular amputees.

BACKGROUND: The Lower Extremity Amputation Protocol (LEAP) is a multidisciplinary enhanced recovery after surgery pathway for vascular amputees. The objective of this study was to examine feasibility and outcomes of community-wide implementation of LEAP. METHODS: LEAP was implemented at three safety net hospitals for patients with peripheral artery disease or diabetes requiring major lower extremity amputation. Patients who underwent LEAP (LEAP) were matched 1:1 with retrospective controls (NOLEAP) on hospital location, need for initial guillotine amputation, and final amputation type (above- vs below-knee). Primary endpoint was postoperative hospital length of stay (PO-LOS). RESULTS: A total of 126 amputees (63 LEAP and 63 NOLEAP) were included with no difference between baseline demographics and co-morbidities between the groups. After matching, both groups had the same prevalence of amputation level (76% below-knee vs 24% above-knee). LEAP patients had shorter duration of postamputation bed rest (P = .003) and were more likely to receive limb protectors (100% vs 40%; P ≤ .001), prosthetic counseling (100% vs 14%; P ≤ .001), perioperative nerve blocks (75% vs 25%; P ≤ .001), and postoperative gabapentin (79% vs 50%; P ≤ .001). Compared with NOLEAP, LEAP patients were more likely to be discharged to an acute rehabilitation facility (70% vs 44%; P = .009) and less likely to be discharged to a skilled nursing facility (14% vs 35%; P = .009). The median PO-LOS for the overall cohort was 4 days. LEAP patients had a shorter median PO-LOS (3 [interquartile range, 2-5] vs 5 [interquartile range, 4-9] days; P < .001). On multivariable logistic regression, LEAP decreased the odds of a PO-LOS of ≥4 days by 77% (odds ratio, 0.23; 95% confidence interval, 0.09-0.63). Overall, LEAP patients were significantly less likely to have phantom limb pain (5% vs 21%; P = .02) and were more likely to receive a prosthesis (81% vs 40%; P ≤ .001). In a multivariable Cox proportional hazards model, LEAP was associated with an 84% reduction in time to receipt of prosthesis (hazard ratio, 0.16; 95% confidence interval, 0.085-0.303; P < .001). CONCLUSIONS: Community wide implementation of LEAP significantly improved outcomes for vascular amputees demonstrating that utilization of core ERAS principles in vascular patients leads to decreased PO-LOS and improved pain control. LEAP also affords this socioeconomically disadvantaged population a greater opportunity to receive a prosthesis and return to the community as a functional ambulator.

Identification of Myocardial Insulin Resistance by Using Liver Tests: A Simple Approach for Clinical Practice.

BACKGROUND: We report that myocardial insulin resistance (mIR) occurs in around 60% of patients with type 2 diabetes (T2D) and was associated with higher cardiovascular risk in comparison with patients with insulin-sensitive myocardium (mIS). These two phenotypes (mIR vs. mIS) can only be assessed using time-consuming and expensive methods. The aim of the present study is to search a simple and reliable surrogate to identify both phenotypes. METHODS: Forty-seven patients with T2D underwent myocardial [18F]FDG PET/CT at baseline and after a hyperinsulinemic-euglycemic clamp (HEC) to determine mIR were prospectively recruited. Biochemical assessments were performed before and after the HEC. Baseline hepatic steatosis index and index of hepatic fibrosis (FIB-4) were calculated. Furthermore, liver stiffness measurement was performed using transient elastography. RESULTS: The best model to predict the presence of mIR was the combination of transaminases, protein levels, FIB-4 score and HOMA (AUC = 0.95; sensibility: 0.81; specificity: 0.95). We observed significantly higher levels of fibrosis in patients with mIR than in those with mIS (p = 0.034). In addition, we found that patients with mIR presented a reduced glucose uptake by the liver in comparison with patients with mIS. CONCLUSIONS: The combination of HOMA, protein, transaminases and FIB-4 is a simple and reliable tool for identifying mIR in patients with T2D. This information will be useful to improve the stratification of cardiovascular risk in T2D.

Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial.

RATIONALE & OBJECTIVE: Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD. STUDY DESIGN: Phase 2, randomized, controlled, open-label, crossover trial. SETTING & PARTICIPANTS: Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs)>15mL/min/1.73m2 and residual proteinuria with protein excretion≥0.5g/24h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy. INTERVENTION: After stratification by serum phosphate level, ≤4 or>4mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period. OUTCOMES: The primary outcome was 24-hour proteinuria (n=49patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness. RESULTS: Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24h) sevelamer were similar (P=0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer. LIMITATIONS: Short treatment duration, lower pretreatment proteinuria than expected. CONCLUSIONS: 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria. FUNDING: Sanofi (Milan, Italy). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01968759.

Phenotyping Type 2 Diabetes in Terms of Myocardial Insulin Resistance and Its Potential Cardiovascular Consequences: A New Strategy Based on 18F-FDG PET/CT.

BACKGROUND: Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). However, the role of myocardial insulin resistance (mIR) remains to be clarified. METHODS: Two 18F-FDG PET/CT scans were performed on forty-three T2D patients at baseline and after hyperinsulinemic-euglycemic clamp (HEC). Myocardial insulin sensitivity (mIS) was determined by measuring the increment in myocardial 18F-FDG uptake after HEC. Coronary artery calcium scoring (CACs) and myocardial radiodensity (mRD) were assessed by CT. RESULTS: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial 18F-FDG uptake and twenty-six a marginal increase, thus revealing mIS and mIR, respectively. Patients with mIR showed higher mRD (HU: 38.95 [33.81-44.06] vs. 30.82 [21.48-38.02]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. CONCLUSIONS: 18F-FDG PET combined with HEC is a reliable method for identifying patients with mIR. This subgroup of patients was found to be specifically at high risk of developing cardiovascular events and showed myocardial structural changes. Moreover, the gold-standard HOMA-IR index was only associated with mIR in this subgroup of patients. Our results open up a new avenue for stratifying patients with cardiovascular risk in T2D.

Diabetes mellitus in young immigrants from hindustan. A descriptive study.

AIM: To analyze the physiological and clinical characteristics of diabetes mellitus (DM) in young immigrants from Hindustan. MATERIAL AND METHODS: We performed a descriptive analysis of clinical and laboratory variables related to DM in diabetic Hindustanis aged between 15 and 40 years old. Body mass index (BMI) and waist perimeter (WP) were calculated. The immunology of DM and baseline C-peptide were studied and insulin resistance (IR) was determined by Homeostasis Model Assessment: Insulin Resistance (HOMA-IR). RESULTS: The final sample consisted of 30 patients. The prevalence of DM was 0.84%. All patients had DM2 and 50% had high IR. Baseline C-peptide secretion was preserved in all patients. The cut-off points that best predicted IR in this ethnic group were a BMI higher than 25 and a WC of more than 95 cm. CONCLUSIONS: Most young Hindustani immigrants with diabetes have DM2 with preserved baseline insulin secretion and IR. Lower degrees of obesity than in the Spanish population were associated with IR.

Blood Pressure and Metabolic Effects of Acetyl-l-Carnitine in Type 2 Diabetes: DIABASI Randomized Controlled Trial.

CONTEXT: Acetyl-l-carnitine (ALC), a mitochondrial carrier involved in lipid oxidation and glucose metabolism, decreased systolic blood pressure (SBP), and ameliorated insulin sensitivity in hypertensive nondiabetic subjects at high cardiovascular risk. OBJECTIVE: To assess the effects of ALC on SBP and glycemic and lipid control in patients with hypertension, type 2 diabetes mellitus (T2D), and dyslipidemia on background statin therapy. DESIGN: After 4-week run-in period and stratification according to previous statin therapy, patients were randomized to 6-month, double-blind treatment with ALC or placebo added-on simvastatin. SETTING: Five diabetology units and one clinical research center in Italy. PATIENTS: Two hundred twenty-nine patients with hypertension and dyslipidemic T2D >40 years with stable background antihypertensive, hypoglycemic, and statin therapy and serum creatinine <1.5 mg/dL. INTERVENTIONS: Oral ALC 1000 mg or placebo twice daily on top of stable simvastatin therapy. OUTCOME AND MEASURES: Primary outcome was SBP. Secondary outcomes included lipid and glycemic profiles. Total-body glucose disposal rate and glomerular filtration rate were measured in subgroups by hyperinsulinemic-euglycemic clamp and iohexol plasma clearance, respectively. RESULTS: SBP did not significantly change after 6-month treatment with ALC compared with placebo (-2.09 mm Hg vs -3.57 mm Hg, P = 0.9539). Serum cholesterol, triglycerides, and lipoprotein(a), as well as blood glucose, glycated hemoglobin, fasting insulin levels, homeostatic model assessment of insulin resistance index, glucose disposal rate, and glomerular filtration rate did not significantly differ between treatments. Adverse events were comparable between groups. CONCLUSIONS: Six-month oral ALC supplementation did not affect blood pressure, lipid and glycemic control, insulin sensitivity and kidney function in hypertensive normoalbuminuric and microalbuminuric T2D patients on background statin therapy.

Renal and Systemic Effects of Calorie Restriction in Patients With Type 2 Diabetes With Abdominal Obesity: A Randomized Controlled Trial.

In individuals with type 2 diabetes with abdominal obesity, hyperfiltration is a risk factor for accelerated glomerular filtration rate (GFR) decline and nephropathy. In this academic, single-center, parallel-group, prospective, randomized, open-label, blinded end point trial, consenting patients with type 2 diabetes aged >18 years, with waist circumference >94 (males) or >80 (females) cm, serum creatinine <1.2 mg/dL, and normoalbuminuria were randomized (1:1) with permuted blocks to 6 months of a 25% calorie restricted (CR) or standard diet (SD). Primary outcome was measured GFR (iohexol plasma clearance). Analyses were by modified intention to treat. At 6 months, GFR significantly decreased in 34 patients on CR and did not change appreciably in 36 on SD. Changes were significantly different between the groups. GFR and body weight reduction were correlated. GFR reduction was larger in hyperfiltering (GFR >120 mL/min) than nonhyperfiltering patients and was associated with BMI, waist circumference, blood pressure, heart rate, HbA1c, blood glucose, LDL-to-HDL cholesterol ratio, C-reactive protein, angiotensin II, and albuminuria reduction and with increased glucose disposal rate (measured by hyperinsulinemic-euglycemic clamps). Protein and sodium intake and concomitant treatments were similar between the groups. CR was tolerated well. In patients with type 2 diabetes with abdominal obesity, CR ameliorates glomerular hyperfiltration, insulin sensitivity, and other cardiovascular risk factors, effects that might translate into long-term nephro- and cardioprotection.

Utility of the mini-cog for detection of cognitive impairment in primary care: data from two spanish studies.

Objectives. To study the utility of the Mini-Cog test for detection of patients with cognitive impairment (CI) in primary care (PC). Methods. We pooled data from two phase III studies conducted in Spain. Patients with complaints or suspicion of CI were consecutively recruited by PC physicians. The cognitive diagnosis was performed by an expert neurologist, after formal neuropsychological evaluation. The Mini-Cog score was calculated post hoc, and its diagnostic utility was evaluated and compared with the utility of the Mini-Mental State (MMS), the Clock Drawing Test (CDT), and the sum of the MMS and the CDT (MMS + CDT) using the area under the receiver operating characteristic curve (AUC). The best cut points were obtained on the basis of diagnostic accuracy (DA) and kappa index. Results. A total sample of 307 subjects (176 CI) was analyzed. The Mini-Cog displayed an AUC (±SE) of 0.78 ± 0.02, which was significantly inferior to the AUC of the CDT (0.84 ± 0.02), the MMS (0.84 ± 0.02), and the MMS + CDT (0.86 ± 0.02). The best cut point of the Mini-Cog was 1/2 (sensitivity 0.60, specificity 0.90, DA 0.73, and kappa index 0.48 ± 0.05). Conclusions. The utility of the Mini-Cog for detection of CI in PC was very modest, clearly inferior to the MMS or the CDT. These results do not permit recommendation of the Mini-Cog in PC.