Long-term outcome of kidney transplantation in patients with a urinary conduit: a case–control study

Purpose

To study the short- and long-term outcomes of kidney transplantation in patients with a bladder augmentation or urinary diversion compared to patients with a kidney transplantation in a normal functional bladder.

Patients and methods

Between January 2000 and March 2011, 13 patients received 16 grafts into a reconstructed urinary tract. We performed a retrospective case–control study and matched each patient to 4 controls for donor and recipient gender and year of transplantation.

Results

Short- and long-term complications of kidney transplantation occurred in 12 patients, varying from urinary tract infections to medical hospitalization with or without surgical or radiological intervention. In 5 patients, a percutaneous nephrostomy (PCN) was placed followed by surgical re-intervention. In three patients, the grafts failed as a result of chronic rejection and were re-transplanted. There was no graft loss as a result of surgical complications or the reconstructed urinary tract. One-year patient and graft survival was 100 %. After five years, all patients were alive and seven of nine grafts (77.8 %) were functioning. Mean follow-up time was 4.3 years. Among the controls, 55 grafts were transplanted in 52 patients. Ten patients received a PCN. Five patients needed surgical re-intervention. In three patients, transplantectomy was performed for ongoing rejection. Three patients were re-transplanted. One patient had a failing graft 7.5 years post-transplantation and became dialysis dependent.

Conclusion

Kidney transplantation in patients with a reconstructed urinary tract has an increased complication rate. Nevertheless, the long-term results are comparable to patients with a normal urinary bladder.     

Self‐regulatory skills: Are they helpful in the prevention of overuse injuries in talented tennis players?

Talented athletes use metacognitive skills to improve their performance. Also, it is known that these skills are important for managing one's health. The goal of this study was to identify the relationship between metacognitive skills and overuse injuries in talented tennis players. Metacognitive skills were measured in 73 talented tennis players (45 boys and 28 girls, age 11‐14) at the start of the season, using the Self‐Regulation of Learning Self‐Report Scale. Overuse injuries were monitored for one season using the Oslo Sports Trauma Research Centre Questionnaire on Health Problems. Ordinal regression indicated that moderate or low selfmonitoring skills (compared to high selfmonitoring) (OR 4.555, CI 1.096‐18.927, P = 0.037) and exposure time (OR 1.380, CI 1.106‐1.721, P = 0.004) were associated with more time loss overuse injuries. A second analysis showed that this was the case in girls (OR 10.757, CI 1.845‐62.714, P = 0.008), but not in boys. Linear regression revealed that higher reflection scores and exposure time predicted overuse severity (F(5,58) = 2.921, P = 0.020, R² = 0.201). Possibly, selfmonitoring can help players to prevent themselves from time loss overuse injuries. Coaches should be aware that players can differ in selfmonitoring ability and thus in the ability to prevent overuse injuries. The role of reflection needs more research.     

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized,Double-Blind Primary Endpoint

ObjectivePublished reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease.Materials and MethodsParticipants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life.ResultsThe study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period.ConclusionDirectional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.     

A diagnostic study in patients with sciatica establishing the importance of localization of worsening of pain during coughing,sneezing and straining to assess nerve root compression on MRI

Purpose

To test whether the localization of worsening of pain during coughing, sneezing and straining matters in the assessment of lumbosacral nerve root compression or disc herniation on MRI.

Methods

Recently the diagnostic accuracy of history items to assess disc herniation or nerve root compression on magnetic resonance imaging (MRI) was investigated. A total of 395 adult patients with severe sciatica of 6–12 weeks duration were included in this study. The question regarding the influence of coughing, sneezing and straining on the intensity of pain could be answered on a 4 point scale: no worsening of pain, worsening of back pain, worsening of leg pain, worsening of back and leg pain. Diagnostic odds ratio’s (DORs) were calculated for the various dichotomization options.

Results

The DOR changed into significant values when the answer option was more narrowed to worsening of leg pain. The highest DOR was observed for the answer option ‘worsening of leg pain’ with a DOR of 2.28 (95 % CI 1.28–4.04) for the presence of nerve root compression and a DOR of 2.50 (95 % CI 1.27–4.90) for the presence of a herniated disc on MRI.

Conclusions

Worsening of leg pain during coughing, sneezing or straining has a significant diagnostic value for the presence of nerve root compression and disc herniation on MRI in patients with sciatica. This study also highlights the importance of the formulation of answer options in history taking.

     

Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5-Year Data From the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension

Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.     

Salmonid alphavirus glycoprotein E2 requires low temperature and E1 for virion formation and induction of protective immunity

Salmonid alphavirus (SAV; also known as Salmon pancreas disease virus; family Togaviridae) causes pancreas disease and sleeping disease in Atlantic salmon and rainbow trout, respectively, and poses a major burden to the aquaculture industry. SAV infection in vivo is temperature-restricted and progeny virus is only produced at low temperatures (10–15 °C). Using engineered SAV replicons we show that viral RNA replication is not temperature-restricted suggesting that the viral structural proteins determine low-temperature dependency. The processing/trafficking of SAV glycoproteins E1 and E2 as a function of temperature was investigated via baculovirus vectors in Sf9 insect cells and by transfection of CHSE-214 fish cells with DNA constructs expressing E1 and E2. We identified SAV E2 as the temperature determinant by demonstrating that membrane trafficking and surface expression of E2 occurs only at low temperature and only in the presence of E1. Finally, a vaccination-challenge model in Atlantic salmon demonstrates the biological significance of our findings and shows that SAV replicon DNA vaccines encoding E2 elicit protective immunity only when E1 is co-expressed. This is the first study that identifies E2 as the critical determinant of SAV low-temperature dependent virion formation and defines the prerequisites for induction of a potent immune response in Atlantic salmon by DNA vaccination.