Automated production of [18F]FTHA according to GMP

14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid is a tracer for fatty acid imaging by positron emission tomography. High demand for this tracer required us to replace semiautomatic synthesis with a fully automated procedure. An automated synthesis device was constructed in‐house for multistep nucleophilic ¹⁸F‐fluorination and a control system was developed. The synthesis device was combined with a sterile filtration unit and both were qualified. 14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid was produced according to good manufacturing practice guidelines set by the European Union. The synthesis includes an initial nucleophilic labelling reaction, deprotection, preparative HPLC separation, purification of the final product, and formulation for injection. The duration and temperature of the reaction and hydrolysis were optimized, and the radiochemical stability of the formulated product was determined. The rotary evaporator used to evaporate the solvent after HPLC purification was replaced with solid phase extraction purification. We also replaced the human serum albumin used in the earlier procedure with a phosphate buffer‐ascorbic acid mixture in the final formulation solution. From 2011 to 2016, we performed 219 synthesis procedures, 94% of which were successful. The radiochemical yield of 14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid, decay‐corrected to the end of bombardment, was 13% ± 6.3%. The total amount of formulated end product was 1.7 ± 0.8 GBq at end of synthesis.     

Salbutamol‐induced Decrease in Augmentation Index is Related to the Parallel Increase in Heart Rate

The change in augmentation index following salbutamol inhalation has been applied to evaluate endothelial function. We examined the contribution of salbutamol‐induced increase in heart rate to the observed decrease in augmentation index. Haemodynamics were recorded using whole‐body impedance cardiography and continuous pulse wave analysis from tonometric radial blood pressure. All subjects (n = 335, mean age 46, body mass index 26, 48% men) were without medications with cardiovascular influences. The effects of salbutamol inhalation (0.4 mg) versus the endothelium‐independent agent nitroglycerin resoriblet (0.25 mg) were examined during passive head‐up tilt, as the haemodynamic influences of these compounds depend on body position. Salbutamol decreased augmentation index by ~3‐4% units in supine and upright positions. Although salbutamol moderately increased cardiac index (+4.5%) and decreased systemic vascular resistance (?8.5%), the significant haemodynamic explanatory factors for decreased augmentation index in multivariate analysis were increased supine heart rate, and increased upright heart rate and decreased ejection duration (p < 0.001 for all, r² = 0.36–0.37). Sublingual nitroglycerin decreased supine and upright augmentation index by ~15% units and ~23% units, respectively. The haemodynamic explanatory factors for these changes in multivariate analysis were increased heart rate, reduced ejection duration and reduced systemic vascular resistance (p ≤ 0.021 for all, r² = 0.22–0.34). In conclusion, the lowering influence of salbutamol on augmentation index may be largely explained by increased heart rate, suggesting that this effect may not predominantly reflect endothelial function.     

Case for staged thyroidectomy

Recent modifications in the management of well‐differentiated thyroid cancer have resulted in significant alterations in clinical approach. Utilizing a series of preoperative and postoperative risk factors involving both the patient and the disease pathology, we offer the term “staged thyroidectomy” to help organize these risk factors for patients and the endocrine team to optimize management. This approach is intended to incorporate our latest nuanced understanding of certain endocrine pathology and may serve to optimize patient outcomes.     

Repeated metal ion measurements in patients with high risk metal-on-metal hip replacement

Purpose

Conventional follow-up methods are not sufficient to identify adverse soft tissue reactions in patients with metal-on-metal hip replacements. The national guidelines regarding metal ion measurements are debatable. The aims of our study were to investigate (1) if there is a clinically significant change in whole blood (WB) cobalt (Co) or chrome (Cr) levels in repeated WB assessment in patients operated on with ASR hip replacements, and (2) what proportion of patients has WB Co or Cr level below the previously established safe upper limits (SUL) in the repeated WB metal ion assessment.

Methods

We identified all patients (n = 254) with unilateral ASR implants who had second blood sample taken eight to 16 months after the first.

Results

WB Co and Cr levels remained below SUL and within their initial values during a mean one-year measurement interval in the majority of patients with a high risk HR device. In contrast to this, 50 % of patients with THRs had metal ion levels exceeding the SUL in the first measurement. WB Co values significantly increased over the measurement interval in the THR group.

Conclusion

In patients with a high risk HR, repeated metal ion measurement did not provide useful information for clinical decision-making. In patients with a LD MoM THR repeated measurements revealed a large number of patients with metal ion levels exceeding SUL and might thus be clinically beneficial.     

Total Knee Arthroplasty with an Uncemented Trabecular Metal Tibial Component : A Registry-Based Analysis

Previous poor results have kept the appeal of uncemented total knee arthroplasties (TKAs) minimal. We analyzed the mid-term survivorship and reasons for failures of a contemporary uncemented porous tantalum monoblock tibial component nation-wide. During the study period (2003–2010), such tibial components were used in 1143 primary TKAs recorded in the Finnish Arthroplasty Registry. Seven-year survivorship of these TKAs was 100% (95% CI 99–100) with revision for aseptic loosening of the tibial component, and 97% (95% CI 96–98) with revision for any reason as the respective end points. The most common reasons for revisions were instability and prosthetic joint infections. In conclusion, TKAs using an uncemented porous tantalum monoblock tibial component showed excellent mid-term survivorship in a population-based setting.     

Long‐term outcome of intraventricular conduction delays in the general population

BackgroundPrevious population studies have presented conflicting results regarding the prognostic impact of intraventricular conduction delays (IVCD).MethodsWe studied long‐term prognostic impact and the association with comorbidities of eight IVCDs in a random sample of 6,299 Finnish subjects (2,857 men and 3,442 women, mean age 52.8, SD 14.9 years) aged 30 or over who participated in the health examination including 12‐lead ECG. For left bundle branch block (LBBB) and non‐specific IVCD (NSIVCD), two different definitions were used.ResultsDuring 16.5 years’ follow‐up, 1,309 of the 6,299 subjects (20.8%) died and of these 655 (10.4%) were cardiovascular (CV) deaths. After controlling for known clinical risk factors, the hazard ratio for CV death, compared with individuals without IVCD, was 1.55 for the Minnesota definition of LBBB (95% confidence interval 1.04–2.31, p = .032) and 1.27 (95% confidence interval 0.80–2.02, p = .308) for the Strauss’ definition of LBBB. Subjects with NSIVCD were associated with twofold to threefold increase in CV mortality depending on the definition. While right bundle branch block, left anterior fascicular block and incomplete bundle branch blocks were associated with seemingly higher mortality, this was no longer the case after adjustment for age and sex. The presence of R‐R’ pattern was not associated with any adverse outcome.ConclusionsIn a population study with long‐term follow‐up, NSIVCD and Minnesota definition of LBBB were independently associated with CV mortality. Other IVCDs had no significant impact on prognosis. The prognostic impact of LBBB and NSIVCD was affected by the definition of the conduction disorder.