A multidisciplinary approach to forensic biological profiling on a single tooth and nail sample.

INTRODUCTION: Analysis of a single tooth and nail can provide valuable forensic information, including year of birth, year of death, age, sex, DNA-profile, geographic residence during childhood and at time of death and drug exposure. The aim is to minimize the amount of used bodily material and to validate the applicability of a multidisciplinary sampling protocol. METHODS: A nail of the big toe, a tooth and blood of seven deceased individuals were collected postmortem. Collected materials were sampled and segmented in accordance with the multidisciplinary sampling protocol. DNA analysis was conducted on the pulp of the tooth, isotope analysis (Sr, Pb, O and C) on the enamel and 14C-, toxicological and tooth cementum annulation analysis on root segments. DNA-, isotope (Sr, Pb, O and C) -, toxicological-, and 14C -analysis were conducted on toenail segments. The acquired DNA profiles were compared with profiles acquired from blood. RESULTS: Material from seven deceased persons was analysed. 45 out of 56 analyses on dental samples were successful, constituting a success rate of 80%. Additionally, 27 out of 35 analyses were successful on nail samples, yielding a success rate of 77%. DNA-, toxicological and 14C- analyses performed better in nail than in tooth. Isotope analyses performed better in tooth than in nail. A profile with personal characteristics was constructed and matched for 62% of parameters with collected medical information. CONCLUSION: The performed sampling protocol for simultaneous multidisciplinary forensic analysis on a single tooth and nail sample provided applicable results and valuable information.

Successful Systemic and Topical Treatment of Mycobacterium abscessus Otomastoiditis.

Mycobacterium abscessus is an extensively drug-resistant opportunistic pathogen that can cause chronic otomastoiditis. There are no evidence-based treatment regimens for this severe infection. We treated four children with M. abscessus otomastoiditis with a structured regimen of topical imipenem and tigecycline, intravenous imipenem and tigecycline, and oral clofazimine and azithromycin and adjunctive surgery. This structured approach led to cure, with 1 year of follow-up after treatment. Adverse events were frequent, mostly caused by tigecycline.

Adequacy of a hospital-wide standard dose of 7mg/kg bodyweight gentamicin sufficient to achieve an adequate prophylactic maximum serum concentration (Cmax) in burn patients undergoing surgical burn wound treatment.

INTRODUCTION: Pharmacokinetics of drugs can be significantly altered in burn patients. The aim of our study was to validate if the current hospital-wide standard dosage of 7mg/kg total bodyweight gentamicin is sufficient to achieve an adequate prophylactic Cmax (Cmax≥20mg/L). MATERIALS AND METHODS: A prospective observational cohort pharmacokinetic study was conducted in burn patients undergoing surgical burn wound treatment. RESULTS: 36/40 (90%) burn patients undergoing surgical burn wound treatment at Rotterdam Burn Centre (Maasstad Hospital), the Netherlands, achieved adequate prophylactic serum concentrations (Cmax≥20mg/L) after a single prophylactic intravenous dose of 7mg/kg total bodyweight gentamicin. Total Body Surface Area (TBSA) burned and total bodyweight were statistically significantly correlated with the Cmax, with correlation coefficients of -0.316, 0.443 and p values of 0.047, 0.004, respectively. Other covariates (age, time after injury, serum creatinine, dose, gender, intensive care admittance) were not statistically significantly correlated. Occurrence of postoperative infection was limited (n=1), no statistically significant difference was observed between patients with a therapeutic and patients with a subtherapeutic serum concentration. CONCLUSION: The current hospital-wide standard dosage of 7mg/kg total bodyweight is sufficient to achieve an adequate prophylactic Cmax in burn patients undergoing surgical burn wound treatment.

A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation.

Tacrolimus is a critical dose drug with a considerable intrapatient variability (IPV) in its pharmacokinetics. We investigated whether a high IPV in tacrolimus exposure is associated with adverse long-term renal transplantation outcomes. Tacrolimus IPV was calculated from predose concentrations measured between 6 and 12 months post-transplantation of 808 renal transplant recipients (RTRs) transplanted between 2000 and 2010. One hundred and eighty-eight (23.3%) patients reached the composite end point consisting of graft loss, late biopsy-proven rejection, transplant glomerulopathy, or doubling of serum creatinine concentration between month 12 and the last follow-up. The cumulative incidence of the composite end point was significantly higher in patients with high IPV than in patients with low IPV (hazard ratio: 1.41, 95% CI: 1.06-1.89; P = 0.019). After the adjustment for several factors, the higher incidence of the composite end point for RTRs with a high IPV remained statistically significant (hazard ratio: 1.42, 95% CI: 1.06-1.90; P = 0.019). Younger recipient age at transplantation, previous transplantation, worse graft function (at month 6 post-transplantation), and low mean tacrolimus concentration at 1 year post-transplantation were additional predictors for worse long-term transplant outcome. A high tacrolimus IPV is an independent risk factor for adverse kidney transplant outcomes that can be used as an easy monitoring tool to help identify high-risk RTRs.

High within-patient variability in the clearance of tacrolimus is a risk factor for poor long-term outcome after kidney transplantation.

BACKGROUND: We hypothesized that a high within-patient variability in clearance of tacrolimus and mycophenolate mofetil (MMF) would put patients at risk for periods of over- or underimmunosuppression and would thus lead to long-term chronic allograft nephropathy and graft loss after transplantation. METHODS: From 297 patients transplanted between 1 January 2000 and 31 December 2004, the within-patient variability in clearance was calculated from tacrolimus whole-blood concentrations and mycophenolic acid (MPA) plasma concentrations drawn between 6 and 12 months post-transplantation. As a primary outcome, a composite end point consisting of graft loss, biopsy-proven chronic allograft nephropathy and 'doubling in plasma creatinine concentration in the period between t = 12 months post-transplantation and last follow-up' was used. RESULTS: In the study population of 297 patients, 34 patients reached the primary end point of graft failure. The within-patient variability in the clearance of tacrolimus and three other covariates are significant risk factors for reaching the composite end point of failure [P-values for intraindividual tacrolimus variability = 0.003, biopsy-proven acute rejection (BPAR) = 0.003, recipient age at transplantation = 0.005]. The mean tacrolimus concentration for controls [7.4 (+/- 2.9) ng/mL] and for failures [6.9 (+/- 2.5) ng/mL] was similar. Within-patient variability in the clearance of MPA was not related to reaching the composite end point of failure. CONCLUSIONS: This study shows a significant relationship between the high within-patient variability in the clearance of tacrolimus, but not for MPA, and long-term graft failure.