Computer-assisted open reduction internal fixation of intraarticular radius fractures navigated with patient-specific instrumentation, a prospective case series.

BACKGROUND: Intra-articular fractures are associated with posttraumatic arthritis if inappropriately treated. Exact reduction of the joint congruency is the main factor to avoid the development of arthrosis. Aim of this study was to evaluate feasibility of computer-assisted surgical planning and 3D-printed patient-specific instrumentation (PSI) for treatment of distal intraarticular radius fractures. METHOD: 7 Patients who suffered a distal intraarticular radius fracture were enrolled in this prospective case series. Preoperative CT-scan was recorded, whereupon a 3D model was computed for surgical planning and design of PSI for surgical navigation. Postoperative accuracy and joint congruency were assessed. Patients were followed-up 3, 6 and 12 months postoperatively. RESULTS: Mean follow-up was 16 months. Over all range of motion was restored and flexion, extension and pronation showed significant recovery, p < 0.05. Biggest intraarticular joint step-off and gap reduced from average 2.49 (± 1.04) to 0.8 mm (± 0.44), p < 0.05 and 6.12 mm (± 1.04) to 2.21 mm (± 1.16), p < 0.05. Average grip strength restored (3-16 months) from 20.33 kg (± 7.12) to 39.3 kg (± 19.55) p < 0.05, 100% of the healthy contralateral side. 3D-accuracy for guided fragments was 2.07 mm (± 0.64) and 8.59° (± 2.9) and 2.33 mm (± 0.69) and 12.86° (± 7.13), p > 0.05 for fragments reduced with ligamentotaxis. CONCLUSION: Computer-assisted and PSI navigated intraarticular radius fracture treatment is feasible, safe and accurate. The benefits of this method, however, do not outstand the additional effort. LEVEL OF EVIDENCE: IV.

[Sport climbing, bouldering and associated injuries in childhood and adolescence]. / Sportklettern, Bouldern und assoziierte Verletzungen im Kindes- und Jugendalter.

BACKGROUND: Sport climbing and bouldering has developed from a rarely performed to a very popular sport in the last 30 years. Sport physicians are increasingly faced with its specific and otherwise uncommon injury pattern. Overall, the sport is relatively safe, particularly if performed in indoor facilities. INJURIES: The injuries frequently occur on the upper extremity, with the fingers being the most affected. Acute traumatic lesions such as sprains, fractures or ligament lesions are much rarer than overload and overuse caused by repetitive and highly stressing climbing movements. The most common injury is not the pulley rupture, as in adults, but the epiphyseal stress fracture of the base of the middle phalanx, which occurs practically only in climbing sport. The injury is treated conservatively, has a long recovery time of about 8 months and may lead to joint destruction and arthrosis if missed.

[Evaluation of three-dimensional sonography for antral follicle count in cycling dairy cows]. / Beurteilung der Follikelzahl mittels transrektaler dreidimensionaler Sonographie bei zyklischen Milchkühen.

INTRODUCTION: The objective of the present study was to investigate reliability of transrectal three-dimensional ultrasound (3D-S) for antral follicle count (AFC) in dairy cows. Furthermore individual differences of AFC between cows and the fluctuation of AFC within and between different cycles were evaluated. To test the reliability of 3D-S, AFC was determined on the ovaries of 10 cows in vivo and compared with counts obtained after slaughter using computer tomography. To evaluate cyclic follicle dynamics, six cows were repeatedly examined with 3D-S over a period of two cycles. Using 3D-S, follicles with a mean diameter greater than 2 mm could be recorded. AFC determined with 3D-S and computer tomography showed a significant correlation (r ≥ 0.86, p < 0.05) and values were similar (p ≥ 0.05). AFC differed between individuals (p < 0.0001) and a moderate fluctuation within and between two cycles within the same cow was apparent (p < 0.05). In conclusion, 3D-S is a suitable method for determination of AFC in cattle. AFC differs between cows and cyclic fluctuations are apparent in a lesser extent.

INTRODUCTION: L'objectif de la présente étude était d'étudier la fiabilité de l'échographie tridimensionnelle transrectale (3D-S) pour le comptage des follicules (FC) chez les vaches laitières. Sur la base du nombre de follicules, on a contrôlé s'il y avait des variations individuelles au sein et entre les différents cycles. Pour tester la fiabilité de la 3D-S, le FC a été déterminée in vivo sur les ovaires de 10 vaches et comparé aux résultats obtenus après l'abattage par tomodensitométrie. Pour évaluer les variations cycliques, six vaches ont été examinées à plusieurs reprises par 3D-S sur une période de deux cycles. En utilisant 3D-S, les follicules avec un diamètre moyen supérieur à 2 mm peuvent être visualisés. Le FC déterminé avec 3D-S et la tomodensitométrie ont montré une significatif corrélation (r ≥ 0,86, p.

Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients.

AIMS: To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. METHODS: We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-vildagliptin treatments) was calculated using the Mantel-Haenszel (M-H) method. RESULTS: Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m(2) (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61-1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M-H RR 1.08 (95% CI 0.68-1.70). CONCLUSIONS: This large meta-analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin-treated patients.

Ultrasonographic assessment of reticuloruminal motility in 45 cows.

The goal of this study was to investigate the feasibility of ultrasonographic assessment of reticuloruminal motility in 45 healthy cows. The transducers of five ultrasound machines were connected to a digital video recorder and placed simultaneously at five sites on the left side of the cows to scan the reticulorumen (reticulum; ruminal atrium; dorsal sac of the rumen; left longitudinal groove; ruminal recess, caudodorsal and caudoventral blind sacs). The video streams from all five ultrasound machines were recorded synchronously with the same time line and displayed on a single monitor. Time 0 was defined as the start of a biphasic reticular contraction. The reticulum was visualised in all cows and had 11.0 ± 2.12 biphasic contractions in 9 min. The ruminal atrium was visualised in 40 (89%) cows and had 10.7 ± 2.10 contractions in 9 min, which started at the time point 5.0 ± 0.83 sec and lasted 7.0 ± 2.14 sec. Contractions of the dorsal sac of the rumen, visible in all cows, were visualised in 29 (64%) cows. There were 9.5 ± 1.8 contractions in 9 min that started at the time point 4.0 ± 0.85 sec and lasted 8.2 ± 1.04 sec. The left longitudinal groove was seen contracting in 39 (87%) cows. There were 10.2 ± 1.98 contractions in 9 min that started at the time point 4.1 ± 1.81 sec and lasted 7.8 ± 1.19 sec. Contractions of the ventral sac of the rumen (ruminal recess) were seen in 31 (69%) cows. There were 7.5 ± 2.59 contractions in 9 min that started at the time point 14.3 ± 4.30 sec. Contractions of the caudodorsal and caudoventral blind sacs were seen in 34 (76%) cows. There were 9.0 ± 2.75 (1.0 ± 0.31) contractions/min and 9.4 ± 2.09 (1.0 ± 0.23) contractions/min of the dorsal and ventral blind sacs, and they started at the time points 6.2 ± 1.32 sec and 21.3 ± 6.20 sec, respectively. Primary contraction cycles were seen in all cows and secondary cycles in 22 (49%) cows. The former were complete in 37 (82%) cows and incomplete in 8 (18%). There were 11.0 ± 2.12 primary and 4.5 ± 2.15 secondary cycles in 9 min, and the ratio between primary and secondary cycles averaged 2.4:1. Ultrasonography is suitable for the assessment of reticuloruminal motility

Glucagon dynamics during hypoglycaemia and food-re-challenge following treatment with vildagliptin in insulin-treated patients with type 2 diabetes.

AIMS: To determine the effects of dipeptidyl peptidase-4 (DPP-4) inhibition on glucagon dynamics in patients with insulin-treated type 2 diabetes (T2D). METHODS: The study was a single-centre, double-blind, randomized, placebo controlled crossover study in patients with T2D, mean age 59 ± 6 (s.d.) years and mean haemoglobin A1c 7.7 ± 0.8%, treated with exogenous insulin with or without oral antihyperglycaemic agents. Patients received vildagliptin (50 mg BID) or placebo as add-on to insulin for 4 weeks in random order with a 4-week washout in-between. On day 28 of the respective treatment, patients were served a standard meal (500 kcal) followed by a hyperinsulinaemic hypoglycaemic clamp (target 2.5 mmol/l) and a subsequent food re-challenge (700 kcal). The completers population (n = 29) was analysed. RESULTS: Glucose levels were lower with vildagliptin than with placebo during the meal [areas under the curve (AUC) 1.23 ± 0.07 vs. 1.46 ± 0.05 mol/l min, P < 0.001] and similar between the groups during the clamp. During the meal, glucagon levels were lower with vildagliptin (AUC 1.98 ± 0.15 vs. 2.15 ± 0.17 nmol/l min, P = 0.016). In contrast, the glucagon counter-regulation to the insulin-induced hypoglycaemia was sustained by vildagliptin (6.05 ± 1.20 pmol/l during vildagliptin vs.6.94 ± 1.09 pmol/l during placebo, NS). During the food re-challenge after hypoglycaemia, glucagon levels were, again, significantly lower after vildagliptin (AUC 1.30 ± 0.11 vs. 1.52 ± 0.12 nmol/l min, P < 0.039). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels were significantly elevated by vildagliptin compared to placebo during meal, hypoglycaemia and food re-challenge. CONCLUSIONS: Vildagliptin action to block GLP-1 and GIP inactivation by DPP-4 improves glucagon dynamics during hypoglycaemia, hyperglycaemia and food re-challenge.

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). METHODS: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Intraoperative imaging of the distal radioulnar joint using a modified skyline view.

PURPOSE: Nonanatomic reduction of the sigmoid notch in distal radius fractures may lead to limited motion, instability, or pain with pronation and supination. Standard radiological projections only poorly capture the sigmoid notch contours in the axial plane. The purpose of this study was to find an intraoperatively feasible radiological projection that will facilitate an axial view of the distal radioulnar joint. METHODS: We modified a previously described radiographic projection termed the skyline view for evaluating the distal radius axially. We created intra-articular steps at the sigmoid notch in solid foam forearm models to identify the best of 12 projections using an image intensifier. Four observers scored each projection based on the clarity of the sigmoid notch contour and indicated the presence and location of an intra-articular stepoff. RESULTS: The sigmoid notch was best visualized in the modified skyline view with the wrist in extension and 10° to 15° of dorsal forearm angulation relative to the x-ray path. All observers correctly recognized the presence and location of intra-articular steps at the sigmoid notch with this view. The same forearm angulation with the wrist in flexion did not reach equally good visibility of the sigmoid notch. Arm position (wrist flexion, forearm rotation, or forearm angulation) and intra-articular stepoff (none, palmar, or dorsal) were dependent determinates. Elimination of the variable forearm rotation had minimal effect, indicating that forearm rotation is not important for visualization of the sigmoid notch. CONCLUSIONS: The modified skyline view for visualization of the distal radioulnar joint in an axial plane allows good visibility of the sigmoid notch and reliable identification of stepoffs. Further cadaver and in vivo studies are required to verify the validity of this method.

Beta cell function following 1 year vildagliptin or placebo treatment and after 12 week washout in drug-naive patients with type 2 diabetes and mild hyperglycaemia: a randomised controlled trial.

AIMS/HYPOTHESIS: Traditional blood glucose lowering agents do not prevent the progressive loss of beta cell function in patients with type 2 diabetes. The dipeptidylpeptidase (DPP)-4 inhibitor vildagliptin improves beta cell function both acutely and chronically (up to 2 years). Whether this effect persists after cessation of treatment remains unknown. Here, we assessed the insulin secretory capacity in drug-naive patients with type 2 diabetes after a 52 week treatment period with vildagliptin or placebo, and again after a 12 week washout period. METHODS: This study was conducted at a single university medical centre, and was a double-blind, randomised clinical trial in 59 drug-naive patients with type 2 diabetes and mild hyperglycaemia to either vildagliptin 100 mg (n = 29) or placebo (n = 30). Randomisation was performed by a validated 1:1 system. Neither patient, nor caregiver, was informed about the assigned treatment. Inclusion criteria were drug-naive patients ≥30 years, with HbA(1c) ≤7.5% and BMI of 22-45 kg/m(2). The mildly hyperglycaemic patient population was chosen to minimise glucose toxicity as a confounding variable. Beta-cell function was measured during an arginine-stimulated hyperglycaemic clamp at week 0, week 52 and after a 12 week washout period. All patients with at least one post-randomisation measure were analysed (intent-to-treat). RESULTS: Fifty-two week vildagliptin 100 mg (n = 26) treatment increased the primary efficacy variable, combined hyperglycaemia and arginine-stimulated C-peptide secretion (AIR(arg)), by 5.0 ± 1.8 nmol/l × min, while it decreased by 0.8 ± 1.8 nmol/l × min with placebo (n = 25) (between-group difference p = 0.030). No significant between-group difference in AIR(arg) was seen after the 12 week washout period. The between-group difference adjusted mean 52 week changes from baseline was -0.19 ± 0.11, p = 0.098 and -0.22 ± 0.23%, p = 0.343 for HbA(1c) and fasting plasma glucose, respectively. There were no suspected drug treatment-related serious adverse events. CONCLUSIONS/INTERPRETATION: One year treatment with vildagliptin significantly increased beta cell secretory capacity. This effect was not maintained after the washout, indicating that this increased capacity was not a disease modifying effect on beta cell mass and/or function. TRIAL REGISTRATION: ClinicalTrials.gov NCT00260156.

The endoplasmic reticulum-Golgi intermediate compartment.

The recent identification of an endoplasmic reticulum-Golgi intermediate compartment has added to the complexity of the structural and functional organization of the early secretory pathway. Protein sorting along the endoplasmic reticulum-Golgi pathway depends on different signals and mechanisms, some of which guarantee recycling from various levels of the Golgi apparatus to biosynthetically earlier compartments.

Clinical experience with vildagliptin in the management of type 2 diabetes in a patient population ≥75 years: a pooled analysis from a database of clinical trials.

AIM: To report the experience with vildagliptin in a patient population with type 2 diabetes mellitus (T2DM) ≥75 years. METHODS: Efficacy data from seven monotherapy and three add-on therapy to metformin studies, respectively, of ≥24 weeks duration were pooled; effects of 24 weeks of treatment with vildagliptin (50 mg bid) in patients ≥75 years were assessed in these two pooled datasets. Safety data were pooled from 38 studies of ≥12 to ≥104 weeks duration; adverse events (AEs) profiles of vildagliptin (50 mg bid) were evaluated relative to a pool of comparators; 301 patients ≥75 years were analysed. Data in patients <75 years are provided as a reference. RESULTS: Mean age of the elderly population was 77 years. Changes in haemoglobin A1c (HbA1c) with vildagliptin in the patient group ≥75 years were -0.9% from a baseline of 8.3% in monotherapy (p < 0.0001) and -1.1% from a baseline of 8.5% in add-on therapy to metformin (p = 0.0004), and these reductions were similar to those seen in the younger patients. The corresponding weight changes in the elderly patients were -0.9 kg (p = 0.0277) and -0.2 kg [not significant (NS)], respectively, and no confirmed hypoglycaemic events, including no severe events, were reported. AEs, drug-related AEs, serious adverse events (SAEs) and deaths were reported with a lower frequency in older patients receiving vildagliptin than comparators [133.9 vs. 200.6, 14.5 vs. 21.8, 8.8 vs. 16.5 and 0.0 vs. 1.7 events per 100 subject year exposure (SYE), respectively], and the incidence of discontinuations due to AEs was similar in the two groups (7.2 vs. 7.5 events per 100 SYE, respectively). The safety profile of vildagliptin was overall similar in younger and older patients. CONCLUSIONS: Vildagliptin was effective and well-tolerated in type 2 diabetic patients ≥75 years (mean age 77 years).

Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial.

AIM: Assess safety/tolerability and efficacy of the DPP-4 inhibitor vildagliptin in 515 patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment (RI). METHODS: Double-blind, randomized, parallel-group, placebo-controlled, 24-week clinical trial assessing safety and efficacy of vildagliptin (50 mg qd) added to current antidiabetic therapy, in patients with T2DM and moderate or severe RI (GFR ≥ 30 to <50 or <30 ml/min/1.73 m(2) ). RESULTS: The study population comprised of 165 and 129 patients with moderate RI and 124 and 97 patients with severe RI randomized to vildagliptin and placebo, respectively, with most patients receiving background insulin therapy (68 and 81% for moderate and severe RI, respectively). After 24 weeks, the between-treatment difference in the adjusted mean change in A1C was -0.5 ± 0.1% (p < 0.0001) in moderate RI (baseline A1C = 7.9%) and -0.6 ± 0.1% (p < 0.0001) in severe RI (baseline A1C = 7.7%). In patients with moderate RI, similar proportions of those receiving vildagliptin or placebo experienced any AE (68 vs. 73%), any SAE (9 vs. 9%), any AE leading to discontinuation (3 vs. 5%) or death (1 vs. 1%). This was also true for patients with severe RI: AEs (73 vs. 74%), SAEs (19 vs. 21%), AEs leading to discontinuation (9 vs. 6%) and death (2 vs. 4%). CONCLUSIONS: In this 24-week study of 515 patients with T2DM and moderate or severe RI, vildagliptin added to ongoing antidiabetic therapy had a safety profile similar to placebo. Further, relative to placebo, vildagliptin elicited a statistically and clinically significant decrease in A1C in patients with moderate or severe RI.

Mechanisms of action of the dipeptidyl peptidase-4 inhibitor vildagliptin in humans.

Inhibition of dipeptidyl peptidase-4 (DPP-4) by vildagliptin prevents degradation of glucagon-like peptide-1 (GLP-1) and reduces glycaemia in patients with type 2 diabetes mellitus, with low risk for hypoglycaemia and no weight gain. Vildagliptin binds covalently to the catalytic site of DPP-4, eliciting prolonged enzyme inhibition. This raises intact GLP-1 levels, both after meal ingestion and in the fasting state. Vildagliptin has been shown to stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent manner. At hypoglycaemic levels, the counterregulatory glucagon response is enhanced relative to baseline by vildagliptin. Vildagliptin also inhibits hepatic glucose production, mainly through changes in islet hormone secretion, and improves insulin sensitivity, as determined with a variety of methods. These effects underlie the improved glycaemia with low risk for hypoglycaemia. Vildagliptin also suppresses postprandial triglyceride (TG)-rich lipoprotein levels after ingestion of a fat-rich meal and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced TG stores in non-fat tissues. The large body of knowledge on vildagliptin regarding enzyme binding, incretin and islet hormone secretion and glucose and lipid metabolism is summarized, with discussion of the integrated mechanisms and comparison with other DPP-4 inhibitors and GLP-1 receptor activators, where appropriate.

Radiological changes and signs of osteoarthritis in the fingers of male performance sport climbers.

AIM: The aim of this study was to investigate the radiological changes and signs of osteoarthritis in the fingers of performance sport climbers that felt to be from acute mechanical stress placed on the fingers and intense training regime over years. METHODS: A total of 31 male sport climbers who were either strong rock climbers or former members of the Swiss climbing team, and 67 non-climbers participated in the study. Fisher's exact test was used to compare the proportions of signs of osteoarthritis between climbers and non-climbers. For the evaluation of radiological changes, antero-posterior and lateral radiographs were taken of both hands. Distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints of the fingers Dig. II-V on the antero-posterior radiographs were scored for signs of osteoarthritis using an atlas (Altman) method. Osteophytes at the DIP and PIP joints were also evaluated on lateral radiographs and compared to the findings on the antero-posterior radiographs. RESULTS: According to the Kellgren-Lawrence method, 6 out of 31 climbers had evidence of clear signs of osteoarthritis in the fingers, whereas none of the non-climbers developed any signs of osteoarthritis (P≤0.001). Twenty-three climbers had definite signs of osteophytosis using antero-posterior radiographs compared to 31 climbers using lateral radiographs. Lateral radiographs have shown to be more accurate in finding, localizing and rating of osteophytes than antero-posterior radiographs. CONCLUSION: Male climbers have more signs of osteoarthritis compared to male non-climbers at similar age. Development of osteophytes seems to be ordinary in every climber. Lateral radiographs are more accurate in diagnosing osteophytes in climbers than using traditional antero-posterior radiographs.

Triquetrum osteotomy to approach an otherwise inaccessible coronal malunion of the hamate.

Fractures of the hamate are rare, and a clear treatment algorithm does not exist. Nonetheless, surgical treatment is generally recommended for displaced fractures using a dorsal approach. There is also a lack of data on hamate malunion. We present a case of a 28-year-old female with a coronal malunion of the hamate and hamate hook fracture. Because the triquetrum prevented direct access to the fracture, we planned and undertook a transtriquetral coronal osteotomy based on three-dimensional computed tomography imaging data. After removing the bone callus, reduction was possible with subsequent fixation. We recommend performing a transtriquetral osteotomy to treat an otherwise inaccessible fracture or malunion of select hamate fractures.

Feasibility of ultrasound-based measurement of dorsal scaphoid displacement: A 3D-model study.

The present study aimed to develop a reliable dynamic measurement technique, which can be used directly in the outpatient setting, based on dorsal subluxation of the scaphoid on scaphoid shift test. This study was designed to evaluate feasibility and to quantify dorsal subluxation of the scaphoid in relation to the lunate. Based on a scaphoid shift test under ultrasonography, a standardized 3D test model was developed to measure subluxation. Sagittal subluxation ranged between 0 and 6 mm, as checked on the implemented scale. Four hand surgeons trained in ultrasonography (experience level II-V) performed blinded measurements (total of 52, n = 13 per investigator) with a standardized measurement protocol. Dorsal subluxation of the scaphoid was measured in relation to the lunate. Interobserver reliability on intraclass correlation coefficient (ICC) was excellent, at 0.97 (95% confidence interval, 0.930-0.992). Mean overall absolute measurement error was 0.27 mm ± 0.21. Dorsal subluxation of the scaphoid can thus be accurately measured on ultrasound with excellent interobserver reliability, quantifying and improving clinical assessment of scapholunate instability.

Primarily conservative treatment for triple (A2-A3-A4) finger flexor tendon pulley disruption.

Triple finger flexor tendon pulley injuries (A2-A3-A4) are generally reconstructed due to the considerable extent of bowstringing and resulting loss of range of motion (ROM). We present a series of 11 patients (12 cases) with triple pulley lesions. Six cases were diagnosed acutely (<2 weeks after injury), one subacutely (4 weeks), 3 late (>2 months) and 2 incidentally (asymptomatic). All patients but one were climbers. All acute and subacute patients were initially treated with two-pulley protection splint at the centre of the middle and proximal phalanx, proximal interphalangeal (PIP) joint extension splints for 2 months and had occupational therapy to prevent extension deficit. At 6 months' follow-up, the 6 patients with acutely and the 1 subacutely diagnosed injuries were back climbing at the same level. Almost no pain or restriction in daily activities remained; they had full flexion but a slight extension deficit (0-25°). Two of the three patients who were seen and diagnosed late had secondary pulley reconstruction because of persistent pain and increased extension deficit in the PIP joint. Both patients gained almost full range of motion without remaining pain. The third patient was asymptomatic with an extension deficit of 30°. Our case series suggests that early conservative treatment in acute and subacute triple pulley ruptures holds promise to decrease bowstringing, regain full flexion and return to pre-injury climbing level. Delayed diagnosis with delayed treatment is associated with less favorable results. Secondary pulley reconstruction of these chronic injuries yields good results even when performed months after the injury occurred.

Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III type 2 diabetes population.

AIM: To assess the cardiovascular and cerebrovascular (CCV) safety of the dipeptidyl peptidase-IV inhibitor vildagliptin. METHODS: Data were pooled from 25 Phase III studies of vildagliptin, used either as monotherapy or combination therapy, with durations of 12 weeks to > or = 2 years. The safety of vildagliptin [50 mg qd (N = 1393) or 50 mg bid (N = 6116)] was assessed relative to a pool of all comparators [both placebo and active comparators (N = 6061)]. CCV events were adjudicated in a prospective, blinded fashion by an independent CCV adjudication committee. Meta-analysis of confirmed CCV events was performed with Mantel-Haenszel risk ratios (RRs); categories included in the composite endpoint were acute coronary syndrome, transient ischaemic attack (with imaging evidence of infarction), stroke and CCV death. Subgroup analyses by age (< and > or = 65 years), gender and cardiovascular (CV) risk status [high CV risk status defined as a previous history of events in the Standard MedDRA Queries of ischaemic heart disease, cardiac failure, ischaemic cerebrovascular conditions and/or embolic/thrombotic events, arterial) were also carried out. In addition, unadjusted and exposure-adjusted incidences are presented for both the composite endpoint and its components. RESULTS: Relative to all comparators, the RRs for the composite endpoint were < 1 for both vildagliptin 50 mg qd [RR = 0.88; 95% CI (0.37, 2.11)] and vildagliptin 50 mg bid [RR = 0.84; 95% CI (0.62, 1.14)]. The results were consistent across subgroups defined by age, gender and CV risk status, including the higher CV risk subgroups of elderly patients [RR for vildagliptin 50 mg bid vs. all comparators = 1.04; 95% CI (0.62, 1.73)], males [RR = 0.87; 95% CI (0.60, 1.24)] or patients with a high CV risk status [RR = 0.78; 95% CI (0.51, 1.19)]. The exposure-adjusted incidences of each component of the composite endpoint for vildagliptin 50 mg bid were also lower than or similar to those of all comparators. CONCLUSIONS: In a large meta-analysis, vildagliptin was not associated with an increased risk of adjudicated CCV events relative to all comparators in the broad population of type 2 diabetes including patients at increased risk of CCV events.

An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials.

AIM: To assess the safety of vildagliptin versus all comparators (ACs) with regard to organs, systems or tissues of particular interest in type 2 diabetes (T2DM) and areas of potential concern with dipeptidyl peptidase-IV (DPP-4) inhibitors. METHODS: Data were pooled from 38 studies where vildagliptin was given for > or =12 to > 104 weeks in patients with T2DM. Absolute and exposure-adjusted incidence rates and Peto odds ratios (ORs) versus ACs with corresponding 95% confidence intervals (CI) were calculated. RESULTS: There were > 7000 subject-years of exposure (SYE) to vildagliptin 50 mg bid and > 6500 SYE to ACs. For mild hepatic enzyme elevations with and without elevated bilirubin levels, the ORs for vildagliptin 50 mg bid were 1.24 (95% CI: [0.80, 1.93]) and 1.19 (95% CI: [0.29, 4.90]), respectively. The exposure-adjusted incidences of markedly elevated hepatic enzymes and for enzyme elevations with bilirubin > or = 2x ULN with vildagliptin 50 mg bid were < or = those in the ACs group. For hepatic and pancreatitis-related AEs, the ORs for vildagliptin 50 mg bid were 0.87 (95% CI: [0.64, 1.19]) and 0.70 (95% CI: [0.26, 1.88]), respectively, and for any AE in the infections and infestations SOC, this was 1.04 (95% CI: [0.96, 1.13]). The incidences of skin-related AEs were low and the risk with vildagliptin 50 mg bid was not significantly different from ACs [(OR = 1.10 (95% CI: [0.80, 1.51])]. CONCLUSIONS: The present meta-analyses indicate that vildagliptin was not associated with increased risk of hepatic events or hepatic enzyme elevations indicative of drug-induced liver injury, pancreatitis, infections or skin-related toxicity.

Recent advances in the surgical treatment of malunions in hand and forearm using three-dimensional planning and patient-specific instruments.

Malunions of the forearm and hand cause significant disability. Moreover, intraarticular deformities may contribute to early onset osteoarthritis. Such conditions require precise surgical correction in order to improve functional outcomes and prevent early or late complications. The purpose of this study was to describe the technical advantages of accurate anatomical reconstruction using 3D guided osteotomies and patient specific instruments (PSI) in multiple joints of the hand and forearm. Acquisition of three-dimensional (3D) datasets and surgical implementation of PSI was performed in a series of patients between December 2014 and July 2017. Patients had intra- or extra-articular malunions of the forearm, radiocarpal joint, trapeziometacarpal joint, or proximal interphalangeal joint. A previously described 3D surface model that incorporates CT data was used for segmentation (Mimics®, Materialise™, Belgium). For all the cases, CT scans of both forearms were acquired to use the contralateral uninjured side as the anatomic reconstruction template. Computer-assisted assessment of the deformity, the preoperative plan, and the design of PSI are described. Outcomes were determined by evaluating step-off correction, fusion, changes in range of motion (ROM) and grip strength. Six patients were included in the study; all achieved fusion. Improved clinical outcomes including pain reduction, better ROM and grip strength were obtained. Complete correction of intraarticular step-off was achieved in all cases with intraarticular malunions. 3D guided osteotomies are an established surgical treatment option for malunions of the hand and forearm. 3D analysis is a helpful diagnostic tool that provides detailed information about the underlying deformity. PSI can be developed and used for surgical correction with maximal accuracy for both intraarticular step-off and angular deformity.