Real-life after sacral nerve modulation implantation: Rate, reasons, and risk factors for mid-term follow-up discontinuation.

OBJECTIVES: To evaluate follow-up after implantation of a sacral nerve modulation implantable pulse generator (IPG) and to investigate the reasons and risk factors for follow-up discontinuation. MATERIALS AND METHODS: All patients who underwent an IPG implantation to treat lower urinary tract symptoms between 2014-2019 within 6 hospital centers located in the district of "Hauts-de-France" (France) were systematically called during the year 2020 for a standardized (tele)consultation. Patients were divided into 3 distinct profiles according to the regularity of their 5-year postoperative follow-up: "Regular follow-up", "Irregular follow-up" and "Lost to follow-up". The primary outcome was the change in the annual proportion of the 3 follow-up profiles over the 5 years following IPG implantation. As secondary outcomes we described the reasons reported for follow-up discontinuation and looked for risk factors associated with. RESULTS: Overall, 259 patients were included. At the time of data collection, after a mean follow-up of 28.4 (± 19.8) months, 139 patients (53.7%) had a "Regular follow-up", 54 (20.8%) had an "Irregular follow-up" and 66 (25.5%) were "Lost to follow-up". The proportion of patients with a "Regular follow-up" decreased year by year, representing only 46.2% of patients at five-years. 175 patients (67.6%) underwent a standardized (tele)consultation. In multivariate analysis, only "lack of knowledge of the follow-up protocol" was statistically associated with follow-up discontinuation (OR=5.16; 95% CI [2.12-13.57]). CONCLUSION: The proportion of patients followed up after IPG implantation decreased steadily over the years, often related to a lack of therapeutic education.

Mutation-based, short-term "neoadjuvant" treatment allows resectability in stage IVB and C anaplastic thyroid cancer.

INTRODUCTION: Few available data indicate that a mutation-based "neoadjuvant" therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term "neoadjuvant" therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. METHODS: In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. PATIENTS: Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. RESULTS: In all three cases, the "neoadjuvant" therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term "neoadjuvant" treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term "neoadjuvant" therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. CONCLUSIONS: A short-term mutation-based "neoadjuvant" therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

Effects of restricted dietary phosphorus supply during the dry period on productivity and metabolism in dairy cows.

Phosphorus in bovine nutrition is under ongoing scrutiny because of concerns with excessive amounts of P excreted in manure contributing to environmental pollution. Feeding rations with excessive P content, however, still remains common practice, particularly during the transition period, as limited P supply in late gestation and early lactation is thought to present a risk for health and productivity of high-yielding dairy cows. The objectives of this study were to investigate the effect of restricted P supply during the last 4 wk of pregnancy on Ca and P homeostasis during the transition period in high-yielding dairy cows, and to identify possible effects on metabolism and productivity throughout the following lactation. Thirty late-pregnant multiparous dairy cows were randomly assigned to either a dry cow diet with low (LP) or adequate P (AP) content [0.16 and 0.30% P in dry matter (DM), respectively] to be fed in the 4 wk before calving. After calving all cows received the same ration with adequate P content (0.46% P in DM). Blood, milk, and liver tissue samples were obtained during the dry period and the following lactation, DM intake (DMI), body weight, milk production, and disease occurrence were monitored. Plasma was assayed for the concentrations of P, Ca, Na, and K, metabolic parameters, and liver enzyme activities. Liver tissue was analyzed for mineral, triglyceride, cholesterol, and water contents. Repeated-measures ANOVA was used to identify treatment, time, and treatment × time interaction effects. Cows fed LP had lower plasma P concentrations ([Pi]) than AP cows during restricted P feeding, reaching a nadir of 1.1 mmol/L immediately before calving. After calving, plasma [Pi] of LP cows was at or above the level of AP cows and within the reference range for cattle. Symptoms assumed to be associated with hypophosphatemia were not observed, but plasma Ca was higher from 1 wk before to 1 wk after calving in LP cows, which was associated with a numerically lower incidence of clinical and subclinical hypocalcemia in LP cows. Both treatments had a similar 305-d milk yield (12,112 ± 1,298 kg for LP and 12,229 ± 1,758 kg for AP cows) and similar DMI. Plasma and liver tissue biochemical analysis did not reveal treatment effects on energy, protein, or lipid metabolism. The results reported here indicate that restricted dietary P supply during the dry period positively affected the Ca homeostasis of periparturient dairy cows but did not reveal negative effects on DMI, milk production, or metabolic activity in the following lactation. Restriction of P during the dry period was associated with hypophosphatemia antepartum but neither exacerbated postparturient hypophosphatemia, which is commonly observed in fresh cows, nor was associated with any clinical or subclinical indication of P deficiency in early lactation.

Effects of restricted dietary phosphorus supply to dry cows on periparturient calcium status.

Restricted dietary P supply to transition dairy cows has recently been reported to beneficially affect the Ca balance of periparturient cows. The objective of the present study was to determine whether this effect on the Ca balance can be reproduced when limiting the P-restricted feeding to the last 4 wk of gestation. A total of 30 dairy cows in late pregnancy were randomly assigned to a dry cow diet with either low or adequate P content (0.16 and 0.30% P in DM, respectively) to be fed in the 4 wk before expected calving. After calving, all cows received the same lactating cow ration with adequate P content (0.46% P in DM). Blood was collected daily from 4 d antepartum until calving, at calving (d 0), 6 and 12 h after calving (d +0.25 and d +0.5, respectively) and on days +1, +2, +3, +4 and +7 relative to calving. Blood gas analyses were conducted to determine the concentration of ionized Ca in whole blood ([Ca2+]), and plasma was assayed for concentrations of inorganic phosphorus ([Pi]), total calcium, parathyroid hormone ([PTH]), 1,25-dihydroxyvitamin D ([1,25-(OH)2D3]), and CrossLaps ([CTX]), a biomarker for bone resorption (Immunodiagnostic Systems GmbH). Repeated-measures ANOVA was conducted to study treatment, time, and lactation number effects. The mean [Ca2+] in P-deprived cows remained above the threshold of 1.10 mmol/L throughout the study, and values were higher compared with cows on adequate P supply between d 0 and d +2 and on d +4. The [Ca2+] differed between treatments at the sampling times d 0, d +0.25, d +0.5, d +2, and d +4. Plasma [PTH] and [1,25-(OH)2D3] did not differ between treatments, but P-deprived cows had greater [CTX] than cows with adequate P supply at d +1, d +2, and d +7. These results indicate that restricted dietary P supply to during the last 4 wk of the dry period improves the Ca homeostasis of these cows in the first days of lactation, an effect that seems to be primarily driven by increased bone tissue mobilization.

Peak retrograde flow a potential objective management tool to identify young adults with varicocele 'at risk' for a high sperm DNA fragmentation.

INTRODUCTION: Determining which patients are negatively affected by varicocele would enable clinicians to better select those men who would benefit most from surgery. Since conventional semen parameters, have been limited in their ability to evaluate the negative effects of varicocele on fertility, specialized laboratory tests have emerged. OBJECTIVE: To identify clinical and ultrasound parameters (including PRF) which would negatively influence standard and functional semen variables in young adults with a varicocele. DESIGN: Prospective, cross-sectional observational study. SETTING: Antwerp University Hospital, Belgium. PATIENT(S): Young volunteers between 16 and 26 years, Tanner 5, were recruited. INTERVENTION(S): Every participant had a scrotal ultrasound to calculate testicular volumes. If a varicocele was present, the grade, vein diameter, peak retrograde flow (PRF) in supine position and spontaneous reflux in standing position were measured. All participants provided a semen sample. Standard semen parameters were analyzed and sperm DNA fragmentation. MAIN OUTCOME MEASURE(S): Of all clinical and ultrasound parameters tested, PRF was an objective tool identifying young adults with a varicocele. PRF was highlighted by the prevalence of SDF, both in the total and vital fractions of the spermatozoa, providing opportunities to manage such 'at-risk' adolescents/young adults. RESULT(S): Total SDF was significantly increased in grade 3 varicocele compared to grade 1 and 2 but no significant difference with vital SDF or standard descriptive semen parameters was seen. Total and vital SDF on the other hand were significantly increased when PRF was above 38.4 cm/s. Standard semen analysis showed no difference with PRF as an independent predictor. Testicular atrophy index, varicocele vein diameter and spontaneous reflux revealed no significant differences in both the descriptive and functional semen variables. DISCUSSION: Descriptive semen parameters showed no significant difference between the non-varicocele controls and the varicocele group with low and high PRF. Increased PRF negatively influenced sperm quality via increased DNA fragmentation both in the total as in the vital fractions of the semen. CONCLUSION(S): Of all clinical and ultrasound parameters tested, PRF was an objective non-invasive tool to identify varicocele patients at risk for a high SDF.

Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

[Surgical treatment of parathyroid carcinoma : Does the initial en bloc resection improve the prognosis?] / Chirurgie des Nebenschilddrüsenkarzinoms : Verbessert die initiale En-bloc-Resektion die Prognose?

BACKGROUND: Radical en bloc resection of the tumor with ipsilateral hemithyroidectomy and central lymphadenectomy (PTX+HTX) is currently the generally recommended treatment strategy for parathyroid carcinoma (PC) in Germany; however, it remains unclear whether the en bloc resection leads to a prognostic benefit compared to parathyroidectomy (PTX) alone, especially considering disease-free and overall survival. OBJECTIVE: This study analyzed the survival of patients with PC after PTX+HTX compared to patients with PTX. METHODS: Patients with PC were identified from a prospective database and retrospectively analyzed regarding clinicopathological features, surgical treatment, disease-free interval and overall survival. RESULTS: Out of 1705 patients who were operated on because of primary hyperparathyroidism (pHPT), 18 (1.1%) had histologically confirmed PC. In nine patients PTX+HTX was initially performed and the other nine patients received only PTX. After PTX, all of the nine patients developed a recurrence after a median of 18 months (range 7-84 months), while only one patient had a recurrence after PTX+HTX. After PTX a median three (range 2-18) reoperations were indicated for relapse but after PTX+HTX only one patient had to undergo two relapse surgeries (p < 0.001). The recurrence-free survival after PTX+HTX was significantly longer than after PTX (143 vs. 18 months, p = 0.01), while the overall survival of both groups after a median follow-up of 107.5 months did not significantly differ. DISCUSSION: If there is any clinical suspicion of PC, an en bloc resection should be performed to prolong recurrence-free survival and avoid reoperations.

The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases.

BACKGROUND: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. METHODS: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. RESULTS: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1­4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1­13) and dose per fraction (median: 18.5 Gy; range 3­37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. CONCLUSION: After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

[Neuromodulation of lower urinary tract dysfunction]. / Neuromodulation bei Harnblasenfunktionsstörungen.

Neuromodulative procedures such as transcutaneous electrical nerve stimulation (TENS), transcutaneous/percutaneous tibial nerve stimulation (TTNS/PTNS), and sacral neuromodulation (SNM) are promising second-line treatments for refractory lower urinary tract dysfunction. Using these therapies, both storage and voiding disorders but also bowel dysfunction might be successfully treated. Although the mechanism of action of neuromodulation is not well understood, it seems to involve modulation of spinal cord reflexes and brain networks by peripheral afferents (genital/rectal, tibial and sacral afferents in the case of TENS, TTNS/PTNS, and SNM, respectively). Neuromodulative procedures might also be highly effective in the most desperate situations and further relevant developments are expected so that these innovative techniques will most likely become even more important in urology.

[Alternative approaches in thyroid surgery]. / Alternativzugänge in der Schilddrüsenchirurgie.

In thyroid surgery multiple different cervical minimally invasive (partly endoscopically assisted) and extracervical endoscopic (partly robot-assisted) approaches have been developed in the last 20 years. The aim of all these alternative approaches to the thyroid gland is optimization of the cosmetic result. The indications for the use of alternative and conventional approaches are principally the same. Important requirements for the use of alternative methods are nevertheless a broad experience in conventional thyroid operations of the thyroid and adequate patient selection under consideration of the size of the thyroid and the underlying pathology. Contraindications for the use of alternative approaches are a large size of the thyroid gland including local symptoms, advanced carcinomas, reoperations and previous radiations of the anterior neck. The current article gives an overview of the clinically implemented alternative approaches for thyroid surgery. Of those the majority must still be considered as experimental. The alternative approaches to the thyroid gland can be divided in cervical minimally invasive, extracervical endosopic (robot-assisted) and transoral operations (natural orifice transluminal endoscopic surgery, NOTES). Since conventional thyroid operations are standardized procedures with low complication rates, alternative approaches to the thyroid gland are considered critically in Germany. The request for a perfect cosmetic result should not overweigh patients' safety. Only a few alternative approaches (e. g. MIVAT, RAT) can yet be considered as a safe addition in experienced hands in highly selected patients.

Stereotactic body radiotherapy for oligo-metastatic liver disease - Influence of pre-treatment chemotherapy and histology on local tumor control.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. METHODS: 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BEDmax). RESULTS: After adjusting for histology, BEDmax was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BEDmax of 157±80Gy10 or 80±62Gy10 with and without prior chemotherapy, respectively. CONCLUSIONS: Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.

Distribution and sub-types of afferent fibre in the mouse urinary bladder.

AIM: Increased afferent fibre activity contributes to pathological conditions such as the overactive bladder syndrome. Nerve fibres running near the urothelium are considered to be afferent as no efferent system has yet been described. The aim of this study was to identify sub-types of afferent nerve fibres in the mouse bladder wall based on morphological criteria and analyse regional differences. MATERIALS AND METHODS: 27 bladders of six month old C57BL/6 mice were removed and tissues were processed for immunohistochemistry. Cryostat sections were cut and stained for Protein Gene Product 9.5 (PGP), calcitonin gene related polypeptide (CGRP), neurofilament (NF), vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS). RESULTS: In the sub-urothelium, different types of afferent nerve fibre were found, i.e. immunoreactive (IR) to; CGRP, NF, VAChT, and/or nNOS. At the bladder base, the sub-urothelium was more densely innervated by CGRP-IR and VAChT-IR nerve fibres, then at the lateral wall. NF- and nNOS nerves were sparsely distributed in the sub-urothelium throughout the bladder. At the lateral wall the inner muscle is densely innervated by CGRP-IR nerve fibres. NF, VAChT and nNOS nerves were evenly distributed in the different muscle layers throughout the bladder. Nerve fibre terminals expressing CGRP and NF were found within the extra-mural ganglia at the bladder base. CONCLUSIONS: Different types of afferent nerve fibres were identified in the sub-urothelium of the mouse bladder. At the bladder base the sub-urothelium is more densely innervated than the lateral wall by CGRP-IR and VAChT-IR afferent nerve fibres. CGRP and NF afferent nerve fibres in the muscle layer probably relay afferent input to external ganglia located near the bladder base. The identification of different afferent nerves in the sub-urothelium suggests a functional heterogeneity of the afferent nerve fibres in the urinary bladder.

Changes in voiding behavior in a mouse model of Alzheimer's disease.

Besides cognitive decline and behavioral alteration, urinary incontinence often occurs in patients suffering from Alzheimer's disease (AD). To determine whether the transgenic mouse model of AD, APP/PS1 (APP(SL)/PS1(M146L)) mouse, shows alteration of the urinary bladder function and anxiety, as for patients with AD, we examined the urinary marking behavior in relation to affective behavior. At 18 months of age voiding behavior of APP/PS1 and wild type (WT) mice was assessed by using a modified filter paper assay in combination with video tracing, with the cage divided into a center and corner zones. Anxiety-related behavior and locomotion were respectively tested in an elevated zero maze (EZM) and an open field (OF). The APP/PS1 mice urinated more in the center zone than the WT mice. The total volume of markings was significantly lower in the APP/PS1 mice. In both groups, the average volume of a marking in the corner zone was larger than in the center zone. In the EZM, the APP/PS1 mice spent less time in the open arms of the arena, considered as anxiogenic zones, than the WT mice. During the OF task, the APP/PS1 mice covered a longer distance than the WT mice. These findings show that the APP/PS1 mice have a different voiding behavior compared to the WT mice, i.e., urinating with small volumes and voiding in the center of the cage, and suggest that increased locomotor activity and anxiety-related behaviors are factors in the change in voiding pattern in the APP/PS1 mouse.

Elevated resting heart rate in heart transplant recipients: innocent bystander or adverse prognostic indicator?

BACKGROUND: The elevated baseline heart rate (HR) of a heart transplant recipient has previously been considered inconsequential. However, we hypothesized that a resting HR above 100 beats per minute (bpm) may be associated with morbidity and mortality. METHODS: The U.T.A.H. Cardiac Transplant Program studied patients who received a heart transplant between 2000 and 2011. Outpatient HR values for each patient were averaged during the first year post-transplant. The study cohort was divided into two groups: the tachycardic (TC) (HR > 100 bpm) and the non-TC group (HR ≤ 100 bpm) in which mortality, incidence of rejection, and cardiac allograft vasculopathy were compared. RESULTS: Three hundred and ten patients were included as follows: 73 in the TC and 237 in the non-TC group. The TC group had a higher risk of a 10-yr all-cause mortality (p = 0.004) and cardiovascular mortality (p = 0.044). After adjustment for donor and recipient characteristics in multivariable logistic regression analysis, the hazard ratio was 3.9, (p = 0.03, CI: 1.2-13.2) and 2.6 (p = 0.02, CI: 1.2-5.5) for cardiovascular mortality and all-cause mortality, respectively. CONCLUSION: Heart transplant recipients with elevated resting HR appear to have higher mortality than those with lower resting HR. Whether pharmacologically lowering the HR would result in better outcomes warrants further investigation.

The effect of non-surgical weight loss interventions on urinary incontinence in overweight women: a systematic review and meta-analysis.

Although the aetiology of urinary incontinence can be multifactorial, in some cases weight loss could be considered as a part of the therapeutic approach for urinary incontinence in people who are overweight. The objective of this study was to review and meta-analyse the effect of non-surgical weight loss interventions on urinary incontinence in overweight women. Web of Science, PubMed, Pedro, SPORTDiscus and Cochrane were systematically searched for clinical trials that met the a priori set criteria. Data of women who participated in non-surgical weight loss interventions (diet, exercise, medication or a combination) were included in the meta-analysis. After removing duplicates, 62 articles remained for screening on title, abstract and full text. Six articles (totalling 2,352 subjects in the intervention groups) were included for meta-analysis. The mean change in urinary incontinence (reported as frequency or quantity, depending on the study) after a non-surgical weight loss intervention, expressed as standardized effect size and corrected for small sample sizes (Hedges' g), was -0.30 (95%CI = -0.47 to -0.12). This systematic review and meta-analysis shows evidence that a non-surgical weight loss intervention has the potential to improve urinary incontinence and should be considered part of standard practice in the management of urinary incontinence in overweight women.

Beta-adrenergic receptors, from their discovery and characterization through their manipulation to beneficial clinical application.

ß-Adrenergic receptors (ß-AR) are central to the overall regulation of cardiac function. From the first proposed receptor/transmitter concept to the latest clinical ß-blocker trials ß-AR have been shown to play an important role in cardiac disease and heart failure in particular. This study provides a historical perspective, reviews the latest discoveries and beliefs, and discusses the current clinical practices of ß-AR and their modulation with their associated guanine-nucleotide regulatory protein/adenylylcyclasesignal transduction pathways.

How should bladder sensation be measured? ICI-RS 2011.

AIMS: Disturbed bladder sensations, or in broader terms, sensory dysfunctions are increasingly recognized as key elements in the origin and manifestation of symptom syndromes of urinary dysfunction. Adequate assessment of bladder sensation is crucial to improve our understanding of the pathophysiology and treatment of urinary dysfunction. This manuscript summarizes the discussions of a think tank on "How to measure bladder sensation" held at the ICI-RS meeting in 2011. METHODS: Based upon literature reviews on bladder sensation presented at the think tank in the ICI-RS meeting, discussions evolved which were summarized in the ICI-RS report. Different physicians/researchers further elaborated on this report, which is presented in this manuscript. RESULTS: Bladder sensations are not merely the result of bladder distension. Other factors inside the bladder or bladder wall: central processing and/or cognitive manipulation may play an important role. Current methods to measure sensations such as urodynamics, voiding diaries, forced diuresis, electrical stimulation and brain imaging are likely sub-optimal as they only consider part of these factors in isolation. CONCLUSIONS: Different methods to measure bladder sensations have been described and are used in clinical practice. Current methods only address part of the parameters responsible for the generation and perception of urinary sensations. Further focused research is required, and several recommendations are provided.

Do patients with OAB experience bladder sensations in the same way as healthy volunteers? A focus group investigation.

AIMS: To describe the terminology and pattern of bladder sensations experienced during non-invasive rapid bladder filling in a controlled setting in patients with OAB and to compare these results with a previous study conducted in healthy volunteers. METHODS: Three groups of patients with OAB, in total 10 patients, participated in three consecutive focus group sessions. Before each session a strict water loading protocol was given. During the first two sessions, participants described how they experienced their bladder sensations in daily life and during a non-invasive bladder filling with constant focus on their bladder. The third session focused on verifying the interpretation of the data gathered and describing the pattern of sensations. RESULTS: Patients describe their bladder sensations as a pressure or a tingling sensation and the pattern can be described by terms ranging from no sensation to an absolute need to void. The absolute need to void may develop suddenly or more slowly progressive. The mean development of bladder sensation is significantly different between patients and healthy volunteers as well as their average diuresis. CONCLUSIONS: Patients with OAB describe their bladder sensations as a pressure or a tingling sensation. There appear to be two types of urgency: a sudden absolute need to void and a slowly developing absolute need to void. Furthermore bladder sensation develops significantly different in volunteers than in OAB patients.

Development and psychometric evaluation of a dutch questionnaire for the assessment of anorectal and lower urinary tract symptoms.

BACKGROUND AND STUDY AIMS: Epidemiological studies have shown a frequent coexistence of symptoms and diseases affecting the anorectum and lower urinary tract. To further investigate combined symptoms and pathology of both pelvic viscera we developed a self-reported questionnaire, in Dutch, which extensively evaluates habits, complaints and symptoms of both viscera. We describe the construction and the psychometric properties of this questionnaire. PATIENTS AND METHODS: This prospective study was conducted in 56 patients with anorectal symptoms, 41 patients with lower urinary tract symptoms and in a control group of 91 people. The following psychometric properties of the questionnaire were evaluated: content validity, construct validity, criterion validity, test-retest reliability and internal consistency. RESULTS: The questionnaire covered all important domains, was well interpreted and showed good acceptability (content validity). The questionnaire clearly differentiated the patient populations (construct validity). The criterion validity of the questionnaire was excellent. The test-retest reliability of the questionnaire was acceptable in all three the study populations (overall median kappa: 0.64; Inter Quartile Range: 0.56-0.75; mean agreement: 88%). The internal consistency of both anorectal and lower urinary tract symptom questions was high (Crohnbach's alpha of 0.78 and 0.80 respectively). CONCLUSIONS: This questionnaire is a valid and reliable instrument for the assessment of anorectal and lower urinary tract symptoms. It can provide further insights into the epidemiology of concomitant bowel and bladder disorders and, accordingly, can contribute to a more efficient diagnostic and therapeutic approach in patients with such disorders.