Outcomes of Selective Arthrodesis Based on Joints Affected in 33 Feet With Müller-Weiss Disease.

No consensus exists regarding operative treatment of Müller-Weiss disease (MWD). Its only classification is based solely on Méary's angle and serves neither as guide to management nor prognosis. We report on 33 feet that underwent surgery following failed conservative management. Treatment was directed towards joint(s) involved, as determined by clinical examination, plain radiography and SPECT-CT. Thus, surgery consisted of isolated talonavicular in 6 feet, triple in 8, subtalar and talonavicular in 7, talonaviculocuneiform in 4, talonaviculocuneiform with interpositional tricortical iliac crest graft in 6 and pantalar arthrodesis in 2. PROMIS scores for pain interference and depression decreased significantly (p < .001) with significant accompanying increase in physical function (p = .003). Union occurred in 31 of 33 feet (94%) with complete resolution of pain at an average follow-up of 84 months. Of the 2 nonunions, 1 had fracture through the lateral navicular, and the other marked sclerosis and avascularity of the lateral navicular. We describe our pathways for selecting arthrodesis based on the joints affected. Isolated talonavicular arthrodesis was performed in early stages of MWD, which begins at the talonavicular articulation. When disease extended to both sides of the navicular, we performed talonaviculocuneiform arthrodesis. When considering isolated talonavicular, double medial or triple arthrodesis, there should be adequate cancellous bone stock remaining in the lateral part of the navicular, as determined on medial oblique radiographs and CT scan. In case of inadequate bone stock or fracture through the lateral navicular, talonaviculocuneiform arthrodesis with interpositional iliac crest bone graft is recommended.

Towards understanding Müller-Weiss disease from an analysis of 95 cases.

BACKGROUND: The single existing classification of Müller-Weiss Disease (MWD), based solely upon Méary's angle, serves neither as guide for prognosis nor treatment. This accounts for lack of gold standard in its management. METHODS: Navicular compression, medial extrusion, metatarsal lengths, Kite's, lateral and dorsoplantar talo-first metatarsal angles were measured in 95 feet with MWD. Joints involved, presence and location of navicular fracture were recorded. RESULTS: Group 1 "early-onset" MWD feet (n = 11) had greatest compression and medial extrusion, and lowest Kite's angles. All except 1 were index minus and had lateral navicular fracture. Only 1 had moderate degeneration at the talonavicular joint (TNJ) with none requiring surgery yet. Group 2 "Müller-Weissoid" feet (n = 23) had radiologically normal navicular in their fifties and developed MWD on average 5 years later. They had the lowest compression and extrusion, and highest Kite's angles. None had complete fracture. All had TNJ arthritis, with early changes at lateral naviculocuneiform joint (NCJ) in 43%. Group 3 "late-onset" MWD presented in the sixth decade. Only TNJ was involved in Group 3 A (n = 16). Group 3B (n = 20) affected TNJ more than NCJ and had the greatest number of Maceira stage V disease. Group 3 C "reverse Müller-Weiss disease", which affected NCJ more than TNJ (n = 25), had greatest midfoot abduction and overlength of the second metatarsal. No fracture occurred in group 3 A compared to 65% and 32% in groups 3B and 3 C, respectively. CONCLUSIONS: With need to compare like-for-like pathology, the proposed classification provides a common platform for reporting outcomes of different treatments. We theorize pathogenetic pathways in the various groups.

Radiographic analysis of Müller-Weiss disease.

BACKGROUND: The only classification of Müller-Weiss disease (MWD) is based primarily on Méary's talo-first metatarsal angle. It describes increasing sag of the medial longitudinal arch with greater degrees of compression and fragmentation of the navicular. Purportedly, the talar head pushes the subtalar joint into varus and drives the medial pole of the navicular medially, as it protrudes inferiorly and laterally. Its authors stipulated heel varus as a pre-requisite, coining the term 'paradoxical pes planus varus' to define heel varus and flatfoot as hallmark deformities of the condition. METHODS: We measured Méary's and Kite's talocalcaneal angles, heel offset, anteroposterior thickness of the navicular at each naviculocuneiform (NC) joint, medial extrusion of the navicular and calculated percentage compression at each NC joint in 68 consecutive feet presenting with MWD. Morphology and activity at the various peri-navicular joints were studied using SPECT-CT in 45 feet. RESULTS: Inverse relationships between Méary's angle and degree of navicular compression reach statistical significance at NC2 but not at NC3. Strong correlation exists between medial extrusion and percentage compression at NC2 and NC3. Medial extrusion is significantly greater on the affected side in unilateral cases and on the more compressed side in bilateral cases. Significant inverse relationships exist between Kite's angle and percentage compression at both NC2 and NC3 and degree of medial extrusion of the navicular. No correlation was detected between Kite's angle and either heel offset or Méary's angle. Varus heel offset was present in only 33% of cases. The combination of heel varus and negative Méary's angle was present in just 26% of cases, the commonest combination being heel valgus with sagging at 56%. CONCLUSION: Our findings confirm part of Maceira's hypothesized pathomechanism of MWD. Reductions in Kite's talocalcaneal angle confirm that lateral and inferior protrusion of the talar head causes increasing compression and medial extrusion of the navicular. However, such shift of the talar head does not always lead to heel varus. As such, we caution against universal advocacy of lateral displacement calcaneal osteotomy, as the heel is not always in varus in MWD.

Diastereoselective FeCl3·6H2O/NaBH4 Reduction of Oxime Ether for the Synthesis of ß-Lactamase Inhibitor Relebactam.

Relebactam, a potent ß-lactamase inhibitor, in combination with Primaxin is an FDA-approved (Recarbrio) treatment for serious and antibiotic-resistant bacterial infections. An efficient synthesis of key chiral piperidine intermediate 1 suitable for large-scale preparation of relebactam is described. The key steps include a unique highly diastereoselective FeCl3·6H2O/NaBH4 reduction of a chiral oxime ether and chemoselective amidation of the resulting unprotected pipecolic acid. Nuclear magnetic resonance studies and density functional theory calculations were carried out on the substrate-Fe(III) complexes, which shed light on diastereoselective reduction.

Safety and Efficacy of a Truncated Deflation Algorithm for Distal Transradial Access.

PURPOSE: To assess safety and efficacy of a modified rapid hemostasis protocol for distal transradial access (TRA). MATERIALS AND METHODS: A single-center retrospective study of patients undergoing percutaneous image-guided procedures from a distal TRA with rapid deflation hemostasis protocol was performed. Between March 2017 and August 2019, 593 procedures in 434 patients were performed. Mean patient age was 63.5 y (range, 18-94 y). RESULTS: The most common procedures were transarterial chemoembolization (218; 36.8%), abdominal and pelvic embolization (116; 19.6%), yttrium-90 mapping (115; 19.4%), yttrium-90 administration (84; 14.2%), and diagnostic angiography (44; 7.4%). Mean (range) values for clotting parameters were international normalized ratio 1.2 (0.9-3.2), partial thromboplastin time 33.5 s (26-44 s), and platelets 23.4 × 109/L (37-552 × 109/L). A hematoma developed in 7 (1.2%) patients. No radial artery occlusions were encountered during follow-up. Nursing intensity was defined as the number of minutes after the procedure required for assessing and managing the access site for bleeding. The mean nursing intensity was 25.1 min (range, 25-40 min). CONCLUSIONS: The rapid deflation hemostasis protocol for distal TRA at the anatomical snuffbox was feasible and safe. No significant difference or association was found between hematoma formation and clotting parameters after the procedure or type of vascular access equipment used.

Early clinical experience with a touchless image navigation interface for the endovascular suite.

Introduction: The inability to having comprehensive access to all pertinent imaging data related to an endovascular procedure in the sterile field is an unmet need, and its absence may have deleterious effects on decision-making, outcomes and workflow. Current image navigation solutions rely on traditional personal computing interfaces which are difficult to use in the sterile field. Innovative technological solutions are needed to address this need.Material and methods: Utilizing novel hardware and software integration, a human computer interaction (HCI) based platform has been developed through an iterative design and development process, that allows intuitive real-time access to imaging data in the sterile field. Following validation and pre-clinical testing, the platform has been introduced to the endovascular suite for clinical use.Results: Three prospective case-based observational reviews are presented that demonstrate the utility of touchless image navigation in the sterile field in facilitating decision-making and resource utilization during endovascular procedures, while avoiding the cognitive and workflow disturbances inherent in leaving the sterile field or involving non-scrubbed third persons in the image navigation process.Conclusion: Physician engagement and 'needs-based' technological innovation is needed to improve human computer interaction in the endovascular suite, in hopes of positively affecting procedural decision-making, outcomes, and workflow.

Retrievable Inferior Vena Cava Filters: A Tertiary Centre Perspective and Quality Assurance Study.

PURPOSE: To conduct a retrospective review and quality assurance study of inferior vena cava (IVC) filter retrieval over a two-year period at a tertiary care centre. METHODS: Patients who underwent IVC filter placement or retrieval over a two-year period were identified. Medical records were reviewed for patient characteristics, filter indication, time to filter retrieval, and complications. RESULTS: IVC filters were placed in 229 patients between January 1, 2015 and December 31, 2016. 113 retrievals were attempted and 101 filters were successfully retrieved (89.4%). Median time to first retrieval attempt was 48 days (range of 5-728). Seventy-one patients died in the interval after filter insertion before a retrieval attempt at a median time of 27 days (range of 3-430). In 17 patients, retrieval was complicated by or delayed because of penetration of IVC wall (n = 6), large thrombus burden trapped by filter (n = 5), filter tilt or migration (n = 3), and unclear reasons (n = 3). Time-to-first unsuccessful retrieval attempt was 141 days (median). Of all filters placed, 55.9% were never retrieved. Excluding deceased patients with in-situ filters (n = 71) and unsuccessful retrievals left in-situ as permanent filters (n = 5), there remains 52 patients (33%), with a median filter in-situ time of 488 days. CONCLUSION: Our study indicates that as many as 33% of patients may have been lost to follow-up of their in-situ IVC filter. Considering widespread reports of long-term complications and the recent safety alert issued by Health Canada, it is evident that a unified strategy is needed to track patients post filter insertion.

Intraprocedural Parenchymal Blood Volume Is a Predictor of Treatment Response for Chemoembolization in Hepatocellular Carcinoma: Results of a Prospective Study.

PURPOSE: To evaluate cone-beam parenchymal blood volume (PBV) before and after embolization as a predictor of radiographic response to transarterial chemoembolization in unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A phase IIa prospective clinical trial was conducted in patients with HCCs > 1.5 cm undergoing chemoembolization; 52 tumors in 40 patients with Barcelona Clinic Liver Criteria stage B disease met inclusion criteria. Pre- and postembolization PBV analysis was performed with a semiquantitative best-fit methodology for index tumors, with a predefined primary endpoint of radiographic response at 3 months. Analyses were conducted with Wilcoxon signed-rank tests and one-way analysis of variance on ranks. RESULTS: Mean tumoral PBV measurements before and after embolization were 170 mL/1,000 mL ± 120 and 0 mL/100 mL ± 130, respectively. Per modified Response Evaluation Criteria In Solid Tumors, 25 tumors (48%) exhibited complete response (CR), 13 (25%) partial response (PR), 3 (6%) stable disease (SD), and 11 (21%) progressive disease (PD). Statistically significant changes in median PBV (ΔPBV) were identified in the CR (P = .001) and PR (P = .003) groups, with no significant difference observed in SD (P = .30) and PD groups (P = .06). A statistically significant correlation between ΔPBV and tumor response was established by one-way analysis of variance on ranks (P = .036; CR, 200 mL/100 mL ± 99; PR, 240 mL/100 mL ± 370; SD, 64 mL/100 mL ± 99; PD, 88 mL/100 mL ± 129). CONCLUSIONS: Intraprocedural PBV can be used as a predictor of response in index HCC tumors of > 1.5 cm.

Beware the hallucal interphalangeal joint sesamoid in first metatarsophalangeal joint arthrodesis.

BACKGROUND: We describe a previously unreported presentation of the hallucal interphalangeal joint sesamoid (HIPJS) following arthrodesis of the first metatarsophalangeal joint (MTP1). METHODS: Of 438 MTP1 arthrodeses performed over a 13-year period, 12 feet returned with a painful keratoma beneath a gradually hyperextending interphalangeal joint of the great toe (IPJ1) from unexcised, unrecognized or recognized HIPJS. We identified another 7 feet with HIPJS, which did not develop symptoms after MTP1 arthrodesis. Angles at which arthrodesis had been performed were measured. RESULTS: All big toes had been arthrodesed in good position, clinically and radiologically, with no difference between the two groups in angles subtended by the proximal phalanx of the arthrodesed big toe with the ground. Good outcomes followed surgical excision of the symptomatic HIPJS. CONCLUSIONS: The presence of a HIPJS should be excluded in the differential diagnosis of IPJ1 symptoms developing after MTP1 arthrodesis. Furthermore, one should look out for and consider prophylactic excision of a HIPJS at time of MTP1 arthrodesis.

The lateral malleolar bony fleck classified by size and pathoanatomy: The IOFAS classification.

BACKGROUND: This study analyzes position of the peroneal tendons and status of the superior peroneal retinaculum (SPR) whenever a lateral malleolar bony flake fracture occurs. METHODS: Twenty-four patients had a lateral malleolar bony fleck on anteroposterior ankle radiographs, either in isolation or associated with other hindfoot injuries. We studied size of the bony flecks, presence or absence of peroneal tendon dislocation and pathoanatomy on CT scans. RESULTS: In 11 patients, a small bony fleck lies within the superior peroneal retinaculum and contiguous periosteum, which are stripped off the lateral fibula (Class II lesions). Tendons dislocate into the subperiosteal pouch thus formed, resembling Class I lesions without associated bony avulsion. Treatment for Class II is same as for Class I injuries. In 8 patients with a big bony fleck, tendons dislocate into the fracture site and SPR is intact (Class III lesions). In Class IV lesions, observed in 5 patients with 2-part calcaneal fracture/dislocation, SPR remains intact and peroneal tendons are not dislocated. The invariably large fleck results from the displacing lateral calcaneal fragment abutting against the fibula, whereas the dislocating tendons cause the bony avulsions in Classes II and III. CONCLUSIONS: Due to pathoanatomical differences, surgical approach and natural history of neglected lesions differ depending on size of the bony fleck. The SPR must not be incised in case of big Class III flecks.

Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High†pH Dynamic Kinetic Reduction.

Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high-pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding.

Use of blood pool agents with steady-state MRI to assess the vascular system.

Over the past two decades there have been significant advances in the use of magnetic resonance imaging (MRI) to assess the vascular system. New imaging sequences and improvements in magnet design have enabled the creation of higher spatial resolution images. MRI is now a viable alternative imaging modality when compared to both invasive angiography and computed tomographic angiography. The use of blood pool agents has further facilitated the use of MR angiography (MRA); their high molecular weight allows for lower doses of contrast medium administration while their prolonged presence in the blood stream allows for repeated high-quality volumetric imaging of both the arterial and venous circulation. As such, MRA is now no longer constrained by the tight windows for first-pass arterial and venous enhancement, which has resulted in the ability to assess and diagnose a large range of vascular pathologies in both arterial and venous systems. The intent of this review is to highlight MRI findings in common vascular pathologies including peripheral arterial disease (PAD), abnormalities of the abdominal aortic branches, postendovascular aortic aneurysm repair (EVAR) endoleak assessment, popliteal artery entrapment syndrome (PAES), deep venous thrombosis (DVT), vascular thoracic outlet syndrome (TOS), and vascular malformations. In addition, the latest MRI techniques currently used to optimally assess each of these pathologies will be discussed. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;45:1559-1572.

Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin.

A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting-group- and precious-metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael-lactolization-dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade. The synthesis of this complex intermediate utilizes simple starting materials and proceeds in four linear steps.

Transradial Access for Interventional Radiology: Single-Centre Procedural and Clinical Outcome Analysis.

PURPOSE: The study sought to describe a single centre's technical approach to transradial intervention and report on clinical outcomes and safety. METHODS: A total of 749 transradial access (TRA) procedures were performed at a single hospital in 562 patients (174 women and 388 men). Procedures included 445 bland embolizations or chemoembolizations of the liver, 88 uterine artery embolizations, and 148 procedures for Selective Internal Radiation Therapy (Y90), which included mapping and administration. The mean age of the patients was 62 years (range 27-96 years). RESULTS: Four cases (0.5%) required crossover to transfemoral (tortuous anatomy, inability to secure a stable position for embolization, vessel spasm and base catheter not being of a sufficient length). A single asymptomatic, short-segment radial artery occlusion occurred (0.3%), 3 patients (0.4%) developed small hematomas postprocedurally, and 2 patients (0.7%) had transient neurological pain, which was resolved within a week without treatment. It was found that 98% of patients who had a previous femoral access procedure would choose radial access for subsequent procedures. CONCLUSIONS: Transradial access is a safe, effective technique, with a learning curve; however, this procedure has the potential to significantly improve departmental workflow and cost savings for the department and patient experience.

Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial.

BACKGROUND: Patients with radioactive iodine ((131)I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib in the treatment of patients with this type of cancer. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (DECISION), we investigated sorafenib (400 mg orally twice daily) in patients with radioactive iodine-refractory locally advanced or metastatic differentiated thyroid cancer that had progressed within the past 14 months. Adult patients (≥18 years of age) with this type of cancer were enrolled from 77 centres in 18 countries. To be eligible for inclusion, participants had to have at least one measurable lesion by CT or MRI according to Response Evaluation Criteria In Solid Tumors (RECIST); Eastern Cooperative Oncology Group performance status 0-2; adequate bone marrow, liver, and renal function; and serum thyroid-stimulating hormone concentration lower than 0·5 mIU/L. An interactive voice response system was used to randomly allocate participants in a 1:1 ratio to either sorafenib or matching placebo. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival, assessed every 8 weeks by central independent review. Analysis was by intention to treat. Patients in the placebo group could cross over to open-label sorafenib upon disease progression. Archival tumour tissue was examined for BRAF and RAS mutations, and serum thyroglobulin was measured at baseline and at each visit. This study is registered with ClinicalTrials.gov, number NCT00984282, and with the EU Clinical Trials Register, number EudraCT 2009-012007-25. FINDINGS: Patients were randomly allocated on a 1:1 basis to sorafenib or placebo. The intention-to-treat population comprised 417 patients (207 in the sorafenib group and 210 in the placebo group) and the safety population was 416 patients (207 in the sorafenib group and 209 in the placebo group). Median progression-free survival was significantly longer in the sorafenib group (10·8 months) than in the placebo group (5·8 months; hazard ratio [HR] 0·59, 95% CI 0·45-0·76; p<0·0001). Progression-free survival improved in all prespecified clinical and genetic biomarker subgroups, irrespective of mutation status. Adverse events occurred in 204 of 207 (98·6%) patients receiving sorafenib during the double-blind period and in 183 of 209 (87·6%) patients receiving placebo. Most adverse events were grade 1 or 2. The most frequent treatment-emergent adverse events in the sorafenib group were hand-foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash or desquamation (50·2%). INTERPRETATION: Sorafenib significantly improved progression-free survival compared with placebo in patients with progressive radioactive iodine-refractory differentiated thyroid cancer. Adverse events were consistent with the known safety profile of sorafenib. These results suggest that sorafenib is a new treatment option for patients with progressive radioactive iodine-refractory differentiated thyroid cancer. FUNDING: Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals (an Amgen subsidiary).

Incidence and recognition of peroneal tendon dislocation associated with calcaneal fractures.

BACKGROUND: Questions abound regarding natural history and medicolegal implications of untreated peroneal tendon dislocation (PTD) associated with calcaneal fractures. METHODS: We retrospectively analyzed CT scans and anteroposterior ankle radiographs of 79 consecutive calcaneal fractures presenting over 4 years at a single institution. RESULTS: Nineteen patients (24%) had associated PTD, which was initially missed in 10 (53%). Bony fleck was present in 11 (13.75%). Soft tissue swelling at lateral malleolar level, present on radiographs of 18 tendon dislocators (95%), raises likelihood of PTD with increasing specificity the greater the swelling. In 6 patients, surgeons failed to identify on CT spontaneously relocated tendons that then peeped around the posterolateral fibula, a finding not appreciable on 3-dimensional volume-rendering. CONCLUSIONS: Despite a significant association of PTD with calcaneal fractures, it still passes unrecognized all too frequently. Anatomical fracture fixation does not guarantee stable tendon reposition. Further studies are required to elucidate functional outcome of untreated PTD.

Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. METHODS: We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were randomised in a 2:1 ratio (by computer-generated randomisation list and interactive voice response system; preallocated block design (block size 12); stratified by treatment line and geographical region) to receive either oral regorafenib 160 mg daily or placebo, plus best supportive care in both groups, for the first 3 weeks of each 4 week cycle. The study sponsor, participants, and investigators were masked to treatment assignment. The primary endpoint was progression-free survival (PFS). At disease progression, patients assigned placebo could crossover to open-label regorafenib. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01271712. RESULTS: From Jan 4, to Aug 18, 2011, 240 patients were screened and 199 were randomised to receive regorafenib (n=133) or matching placebo (n=66). Data cutoff was Jan 26, 2012. Median PFS per independent blinded central review was 4·8 months (IQR 1·4-9·2) for regorafenib and 0·9 months (0·9-1·8) for placebo (hazard ratio [HR] 0·27, 95% CI 0·19-0·39; p<0·0001). After progression, 56 patients (85%) assigned placebo crossed over to regorafenib. Drug-related adverse events were reported in 130 (98%) patients assigned regorafenib and 45 (68%) patients assigned placebo. The most common regorafenib-related adverse events of grade 3 or higher were hypertension (31 of 132, 23%), hand-foot skin reaction (26 of 132, 20%), and diarrhoea (seven of 132, 5%). INTERPRETATION: The results of this study show that oral regorafenib can provide a significant improvement in progression-free survival compared with placebo in patients with metastatic GIST after progression on standard treatments. As far as we are aware, this is the first clinical trial to show benefit from a kinase inhibitor in this highly refractory population of patients. FUNDING: Bayer HealthCare Pharmaceuticals.

Asymmetric synthesis of cyclic indole aminals via 1,3-stereoinduction.

A general and efficient asymmetric synthesis of cyclic indoline aminals was developed with a high level of 1,3-stereoinduction through a dynamic crystallization-driven condensation. Dehydrogenation of the indoline aminals with potassium permanganate produced the corresponding cyclic indole aminals in high yields and excellent enantioselectivities. This general methodology was successfully applied to the synthesis of a wide variety of chiral cyclic indoline aminals and indole aminals with aromatic and aliphatic functional groups.

Longitudinal changes in isovolumetric bladder pressure in response to age-related prostate growth in 1,020 healthy male volunteers.

AIM: To non-invasively study if compensation and decompensation occurs in the urinary bladder of healthy male volunteers in response to benign prostatic enlargement (BPE) using the condom catheter method. METHODS: Between 2001 and 2010, 1,020 healthy male volunteers were included in a longitudinal study based on three non-invasive urodynamic examinations during a 5-year follow-up. Inclusion criteria were an informed consent, the ability to void in a normal standing position and a minimum free flow rate of 5.4 ml/sec. Study parameters were prostate volume (PV), maximum free urinary flow rate (Q(max)) and bladder contractility, quantified by the maximum isovolumetric bladder pressure, measured in the condom (P(cond.max)). Volunteers also completed the International Prostate Symptom Score Form (IPSS). RESULTS: Within limitations, the included volunteers had a flat age distribution between 38 and 72 years. This made it possible to combine longitudinal analysis in a 5-year observation interval, with cross sectional analysis in a 35-year age range. Longitudinal analysis showed that with increasing age, PV increased with 1.9% per year, whereas Qmax decreased with 1.1% per year. IPSS increased with 1.1% per year when volunteers were older than 55 years. P(cond.max) increased during the 5-year longitudinal follow-up, but not in the cross sectional analysis. CONCLUSIONS: The difference between cross sectional and longitudinal results of the P(cond.max) may have been caused by compensation of the urinary bladder resulting in a selection effect. This would imply that compensation is a relatively fast process, taking approximately 5 years.

Pre-requisites for optimum centering of a tibiotalocalcaneal arthrodesis nail.

BACKGROUND: Purpose of study was to compare nail alignment, incidence of stress riser and fracture with straight and curved nails of different lengths. METHODS: We conducted a retrospective review of consecutive, initially 13 straight and subsequently 15 curved nails implanted in 17 men and 11 women. Angles of incidence and reflection subtended by nail tip with inner tibial cortex were measured. Cortical hypertrophy was assessed on follow-up radiographs. RESULTS: Angles of incidence and reflection were greater with short straight nails, less with long straight nails and stayed close to zero with long curved nails. Stress fractures occurred in 2 patients with straight nails at the level of the proximalmost tibial screw. Cortical hypertrophy was present in 7 patients with straight nails and in only 1 patient with a curved nail (p=0.01). CONCLUSIONS: Both nail length and inbuilt valgus contribute to better central positioning within the tibia. However, cortical stress reactions occur less frequently with curved nails.