Charcot arthropathy outcomes after early referral to a regional tertiary care foot clinic.

BACKGROUND: Community physicians may not encounter Charcot arthropathy frequently, and its symptoms and signs may be nonspecific. Patients often have a delay of several months before receiving a formal diagnosis and referral for specialty care. However, limited Canadian data are available. We evaluated the clinical history, treatment and outcomes of patients treated for Charcot arthropathy after prompt referral and diagnosis. METHODS: We performed a retrospective chart review of 76 patients with diabetes (78 feet) who received nonoperative treatment for Charcot arthropathy in a specialty foot clinic between Jan. 20, 2009, and Mar. 26, 2018. Patients were referred to the foot clinic by community physicians for evaluation or were pre-existing patients at the foot clinic with new-onset Charcot arthropathy. RESULTS: Of the 78 feet included in our analyses, 52 feet (67%) were evaluated initially by a community physician and referred to the foot clinic, where they were seen within 3 ± 5 weeks. The remaining 26 feet (33%) were already being treated at the foot clinic. Most feet had swelling, erythema, warmth, a palpable pulse and loss of protective sensation. Ulcers were present initially in 23 feet (29%). Sixty-four feet (82%) with Charcot arthropathy were in Eichenholtz classification stage 1 and most had midfoot involvement. Nonoperative treatment included total contact casting (60 feet, 77%). Mean duration of nonoperative treatment until resolution for 55 feet (71%) was 6 ± 5 months. Surgery was performed on 20 feet (26%) for the treatment of infection and recurrent ulcer associated with deformity, including 6 (8%) lower limb amputations. CONCLUSION: Charcot arthropathy may resolve in most feet with early referral and nonoperative treatment, but remains a limb-threatening condition.

Binge drinking does not appear to have an adverse effect on non-alcoholic fatty liver disease: Findings from a study of four First Nations communities.

BACKGROUND: Binge drinking and non-alcoholic fatty liver disease (NAFLD) are common health problems throughout the world. However, the impact of binge drinking on NAFLD has yet to be described. The objective of this study was to document the extent of liver disease in community-based NAFLD patients who self-reported monthly binge drinking and compare the findings to NAFLD patients from the same communities who denied binge drinking (controls). METHODS: The study was undertaken in four Manitoba First Nations communities where the sale and consumption of alcoholic beverages are prohibited but visits to urban centres are common. Binge drinkers were retrospectively matched 1:2 by age, sex, and body mass index (BMI) with controls. NAFLD was diagnosed by ultrasonographic features of excess fat in the liver in individuals with no alternative, non-metabolic explanation for fatty infiltration of the liver. Hepatic inflammation and function were determined by standard liver biochemistry testing and fibrosis by FIB-4 levels and hepatic elastography. RESULTS: Of 546 NAFLD patients, 88 (16%) attested to binge drinking. The mean age of binge drinkers was 40 (SD 13) years; 51% were male; and the mean BMI was 34 (SD 7). Compared with controls, binge drinkers had similar liver biochemistry results (alanine and aspartate aminotransferases: 41 [SD 39] and 36 [SD 30] versus 36 [SD 36] and 31 [SD 27] U/L, p = 0.35 and p = 0.37, respectively), FIB-4 values (0.75 [SD 0.55] versus 0.72 [SD 0.44], p = 0.41, respectively), and hepatic elastrography (6.6 [SD 3.9] versus 6.2 [SD 2.9] kPa, p = 0.37, respectively) findings. CONCLUSIONS: In this study population, monthly binge drinking did not appear to impact the severity of NAFLD.

Post-transplant diabetes mellitus in Canadian liver and renal transplant recipients.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) occurs in 10%-40% of liver and renal transplant recipients. Whether the risk factors for PTDM in liver and renal transplant recipients are similar and whether Indigenous Canadians, who have a high underlying prevalence of diabetes mellitus (DM), are at increased risk of developing PTDM have yet to be determined. OBJECTIVE: To describe and compare those variables associated with PTDM in adult Canadian liver and renal transplant recipients. METHODS: A retrospective chart review of adult liver and renal transplant recipients attending four transplant follow-up clinics in three Canadian provinces was undertaken. RESULTS: De novo PTDM was diagnosed in 184/905 (20.3%) liver and 179/390 (45.9%) renal transplant recipients. Older age, higher pre-transplant BMI, underlying immune-mediated liver disease, lower trough tacrolimus levels and longer duration of follow-up were independently associated with PTDM in liver transplant recipients and non-Caucasian race, higher pre-transplant BMI, and incidence of organ rejection in renal transplant recipients. Compared with Caucasians, Indigenous Canadians who had undergone renal transplantation had a significantly increased prevalence of PTDM (56.5% versus 40.0%, p = 0.035). The prevalence of PTDM in liver transplant recipients was similar in Indigenous Canadians and Caucasians (27.9% versus 20.1%, p = 0.215). CONCLUSIONS: The variables associated with PTDM differ in liver and renal transplant recipients. Compared with Caucasians, Indigenous Canadians undergoing renal transplantation are at increased risk of developing PTDM.

Unconjugated hyperbilirubinemia may exacerbate certain underlying chronic liver diseases.

BACKGROUND: Negative correlations have been described between elevated serum unconjugated bilirubin levels and the prevalence/severity of various chronic inflammatory conditions. Whether a similar association exists for patients with unconjugated hyperbilirubinemia (UCB) and underlying chronic liver diseases (CLD) has yet to be reported. The aim of this study was to document hepatic necro-inflammatory disease activity and fibrosis in CLD patients with and without UCB and otherwise normal liver function tests (albumin and INR). METHODS: Necro-inflammatory disease activity was assessed by serum aminotransferase levels and fibrosis by APRI and FIB-4 calculations. UCB patients were matched 1:2 by age, gender, and underlying CLD to patients with normal bilirubin levels. RESULTS: From a database of 9,745 CLD patients, 208 (2.1%) had UCB and 399 served as matched controls. Overall, UCB patients had significantly higher serum aminotransferase levels, APRI, and FIB-4 scores. The differences were driven by patients with underlying chronic viral or immune mediated liver disorders rather than non-alcoholic fatty liver disease, alcohol-related liver disease, or 'other' CLDs. CONCLUSIONS: These results suggest UCB is associated with increased rather than decreased hepatic necro-inflammatory disease activity and fibrosis in patients with certain CLDs.

Pharmacokinetics of a once-daily tacrolimus formulation in first nations and caucasian liver transplant recipients.

Patient ethnicity may influence the pharmacokinetics (PK) of tacrolimus. Because the Canadian First Nations (FN) constitute a large and increasing segment of the liver transplant population, we undertook to determine whether PK differences exist for a once-daily, extended release formulation of tacrolimus (Advagraf) in FN compared to Caucasian (CAUC) liver transplant recipients. Following achievement of a steady state with Advagraf, blood samples were drawn at 0, 1, 2, 4, 6, 8 and 24 hours for whole blood tacrolimus levels by commercial immunoassay and CYP3A4 and CYP3A5 allele analyses were performed by polymerase chain reactions. Nineteen subjects participated in the study (7 FN and 12 CAUC). The FN cohort had significantly higher AUC (214 ± 48 versus 168 ± 25, P < 0.05), Cmax (16.7 ± 4.4 ng/ml versus 11.3 ± 1.7 ng/ml, P < 0.05), Cmin (6.1 ± 1.0 ng/ml versus 4.7 ± 0.5 ng/ml, P < 0.05) and shorter Tmax (1.6 ± 0.2 hours versus 2.8 ± 0.3 hours, P < 0.05) values than CAUCs. CYP3A4 genotypes were C/C in both cohorts, while the CYP3A5 *1/*3 allele was present in 2/5 FN and 0/9 CAUC. The results of this study indicate that once-daily, extended release Advagraf results in higher blood tacrolimus levels and shorter times to Cmax in FN compared to CAUC liver transplant recipients.