Introducing an lsoprenaline Eluting Guidewire: Report on its Design and the Results of the Dose-Determining Pilot Study.

Introduction: Retrograde intrarenal surgery (RIRS) is associated with complications, many of which are related to the intrarenal pressure (IRP). We aim to describe the design of a novel isoprenaline-eluting guidewire ("IsoWire") and present the results from the first in vitro release studies and the first animal studies showing its effect on IRP. Materials and Methods: The IsoWire comprises a Nitinol core surrounded by a stainless-steel wire wound into a tight coil. The grooves created by this coil provided a reservoir for adding a hydrogel coating into which isoprenaline, a beta-agonist, was loaded. Animal studies were performed using a porcine model. For the control, IRP, heart rate (HR), and mean arterial pressure (MAP) were measured continuously for 6 minutes with a standard guidewire in place. For the experiment, the standard hydrophilic guidewire was removed, the IsoWire was inserted into the renal pelvis, and the same parameters were measured. Results: In vitro analysis of the isoprenaline release profile showed that most (63.9 ± 5.9%) of the loaded drug mass was released in the 1st minute, and almost all of the drug was released in the first 4 minutes exponentially. Porcine studies showed a 25.1% reduction in IRP in the IsoWire that released 10 µg in the 1st minute; however, there was a marked increase in HR. The average percentage reduction in IRP was 8.95% and 21.3% in the IsoWire that released 5 and 7.5 µg of isoprenaline, respectively, with no changes in HR or MAP. Conclusions: The IsoWire, which releases 5 and 7.5 µg of isoprenaline in the 1st minute, appears to be safe and effective in reducing the IRP. Further studies are needed to establish whether the isoprenaline-induced ureteral relaxation will render easier insertion of a ureteral access sheath, reduce IRP during sheathless RIRS, or even promote the practice of sheathless RIRS.

Place of urolithiasis in the spectrum of urological pathologies, practices and use of endourological procedures in the management of calculi of the upper urinary tract: results of a survey of referral centres in Africa.

Our aim was to determine the current trend of endourology in the management of upper urinary tract calculi in Africa reference centres. We conducted an online multiple-choice questionnaire survey involving 46 centres from 27 countries using a structured well-designed Google Form (®) questionnaire. The questionnaires were distributed to the head of service through their emails. The questions collected demographic data about the centre, the epidemiology of urolithiasis, diagnostic means and management of upper urolithiasis, especially access to endourology procedures and their practices. Descriptive analyses were performed. The participation rate was 77.9%. Urinary lithiasis was one of the three main pathologies encountered in 42/46 centres. 33 centres had easy access to CT scanners and 34 had operating theatres equipped with endo-urological surgery equipment. Of these 34 centres, 30 perform endourology for the management of upper urinary tract stones. Rigid ureteroscopy is the main technique used by the centres. It is the only endourology technique used for stone management by 12 centres (40%). 7/30 (23.3%) have the option of performing rigid ureteroscopy, flexible ureteroscopy and percutaneous nephrolithotomy. The frequency of procedures varies widely, with 43.3% rarely performing endourological surgery. Seventeen centres have their operating theatre equipped with a fluoroscope and 6/42 centres have extracorporeal lithotripsy. Open surgery is still used in 29/42 centres (69.1%). Laparoscopy is available in 50% of centres, but none reported performing laparoscopic lithotomy. In Africa, urinary lithiasis plays an important role in the activities of referral centres. Modern management techniques are used to varying degrees (not all centres have them) and with very variable frequency. Open surgery is still widely performed as a management. Rigid ureteroscopy is the main endourological technique. It is essential to develop the practice of modern urology in Africa, mainly endourology.

A Pilot Study of a Novel Syphon Ureteral Access Sheath Shows Potential to Reduce Renal Pressures and Improve Irrigant Flow.

OBJECTIVE: To describe a novel syphon ureteral access sheath (UAS) intended for use during flexible uretero-renoscopy (fURS). We aimed to report on a pilot study as well as intrarenal pressures (IRP) and irrigant flow volumes compared to traditional UAS. METHODS: Patients undergoing routine fURS for single, <2cm intrarenal nephrolithiasis were identified, and written informed consent was obtained. Irrigation via the fURS was instilled through the novel 11/13 Fr UAS without (a proxy for a traditional UAS) and with the novel syphon box attached. Measured minute irrigant flow volume, steady state and bolus IRP were compared. RESULTS: Ten participants (6 males and 4 females) were treated with the syphon UAS. All procedures were completed safely without intraoperative complications. The mean baseline IRP with and without the syphon was 18 vs 29 mmHG (P < .001, SD 4.0 vs 4.8). The mean minute irrigant flow volume with and without the syphon was 31 vs 21 ml (P < .001, SD 6.4 vs 3.3). The mean peak IRP following a 10 ml bolus with and without the syphon was 71 vs 104 mmHg (P = .03, SD 74 vs 59). CONCLUSION: The described novel UAS is different from traditional devices by incorporating a syphon mechanism. This pilot trial demonstrates that the novel syphon UAS may hold clinical potential to reduce IRP and increase irrigant flow compared to traditional UAS. Firm conclusions about efficacy and safety require assessment of the device in a larger clinical trial.

IRONMAN: A Novel International Registry of Men With Advanced Prostate Cancer.

PURPOSE: To describe a newly established international registry recruiting diverse patients with advanced prostate cancer across academic and community practices to address unmet needs in this population. PATIENTS AND METHODS: Initiated in 2017, IRONMAN (International Registry for Men with Advanced Prostate Cancer) is a prospective cohort of patients with advanced prostate cancer. The study will enroll 5,000 patients with metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC), recruited from Australia, the Bahamas, Barbados, Brazil, Canada, Ireland, Jamaica, Kenya, Nigeria, Norway, South Africa, Spain, Sweden, Switzerland, the United Kingdom, and the United States. The study is collecting datatypes to study variation in care and treatment of advanced prostate cancer across countries and across academic, community-based, and government practices with a focus on clinical outcomes, patient-reported outcomes, epidemiologic data, biologic subtypes, and clinician questionnaires. RESULTS: Through July 2022, 2,682 eligible patients were enrolled in 11 of 12 active countries. Sixty-six percent of patients have mHSPC, and 34% have CRPC. On the basis of self-report, 11% of patients are Black and 9% are Hispanic. Five Veterans Affairs Medical Centers are enrolling patients. Globally, 23% of patients report being veterans of military service. CONCLUSION: To our knowledge, this is the first international cohort of people newly diagnosed with advanced prostate cancer designed to describe variations in patient management, experiences, and outcomes. IRONMAN aims to identify optimal treatment sequences to improve survival, understand patient-reported outcomes, and explore novel biomarkers to understand treatment resistance mechanisms. Insights from IRONMAN will inform and guide future clinical management of people with mHSPC and CRPC. This cohort study will provide real-world evidence to facilitate a better understanding of the survivorship of people with advanced prostate cancer.

Depression, Anxiety, and Their Association to Health-Related Quality of Life in Men Commencing Prostate Cancer Treatment at Tertiary Hospitals in Cape Town, South Africa.

BACKGROUND: Comorbid depression and anxiety in men with localised prostate cancer (CaP) largely go undiagnosed and untreated and their effects on health-related quality of life (HRQOL) in men with CaP should not be underestimated. We examined the prevalence of depression and anxiety and its association with HRQOL in men about to commence treatment for CaP and the differences between treatment groups, radical prostatectomy (RP) and radiation therapy (RT). METHOD: One hundred and seven participants from a longitudinal prospective observational study assessing depression, anxiety and HRQOL in men with localised CaP (DAHCaP), were used in this cross-sectional analysis. Data were collected shortly before participants were scheduled to receive their treatment. The Centre for Epidemiologic Studies Depression Scale (CES-D), the State Trait Anxiety Inventory (STAI), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), the European Organisation for Research and Treatment in Cancer Quality of Life questionnaire (EORTC QLQ-C30) and (EORTC QLQ-PR25) were used in this analysis. RESULTS: Symptoms of depression pre-treatment were noted in 39.3%, state anxiety 28%, trait anxiety 31.4% and prostate cancer anxiety in 12.1% of participants. Statistically significant correlations (P ≤ .05) with the CES-D and a cluster of symptoms on the EORTC QLQ-C30 domains for Global Health (rs = -.35), fatigue (rs = .38), pain (rs = .32), dyspnoea (rs = .28), insomnia (rs = .30) and finance (rs = .26) and EORTC QLQ-PR25 domains for urinary symptoms (rs = .43), bowel (rs = .43) and hormone replacement therapy (HRT) (rs = .41) were observed.Statistically significant correlations were also noted between the STAI-S and EORTC QLQ-C30 and EORTC QLQ-PR25. No statistically significant difference was noted between treatments. CONCLUSION: More men were depressed than anxious with significant associations with HRQOL prior to commencement of treatment. CaP treatments should focus not only on the prevailing indisposition but include a psychooncological and HRQOL assessment at pre-treatment in high-risk individuals.

Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

Pulmonary lymphangioleiomyomatosis with an associated giant renal angiomyolipoma.

Pulmonary lymphangioleiomyomatosis (LAM), a rare, progressive disease predominantly affecting the lungs of women of reproductive age, is often associated with renal angiomyolipoma (AML). We report the case of a 29-year-old female patient who presented to our obstetrics department at 37 weeks' gestation, complaining of abdominal pain, and constipation. Ultrasound noted a viable singleton with a large left-sided abdominal mass. After undergoing a caesarean section, she was referred to our urology department to assess her flank mass further. Computed tomography demonstrated a large, exophytic left renal mass measuring 22 cm x 16 cm x 13 cm, suggestive of an AML and numerous bilateral pulmonary cysts. A diagnosis of LAM and associated unilateral giant renal AML was made. As soon as she had fully recovered from her caesarean section, we removed the huge AML via a standard left-sided open nephrectomy without incident. We report this rare case of giant AML associated with LAM and review the literature about the association of these two conditions.

Novel syphon ureteric access sheath has the potential to improve renal pressures and irrigant flow.

OBJECTIVE: To describe a novel syphoning ureteric access sheath (UAS) intended for use during flexible ureterorenoscopy (URS). We aimed to assess if in vitro it could reduce intrarenal pressure (IRP) and increase irrigant flow compared to traditional UASs. MATERIALS AND METHODS: A validated phantom kidney with fibre optic pressure sensing capabilities was used to assess the IRP. Standardised 80 cmH2 O irrigation via a ureterorenoscope was instilled through traditional UASs (11/13 and 12/14 F) and compared to the novel 11/13-F syphoning UAS. The measured minute volume, calculated hourly flow volume, and steady state IRP were compared. RESULTS: The traditional 11/13 and 12/14-F UASs had statistically poorer irrigant flow than the novel syphoning UAS, at 19.3 vs 29.3 mL/min (P < 0.001) and 22.7 vs 29.3 mL/min (P = 0.002), respectively. The steady state IRP was 20 mmHg for the traditional 11/13 F and 13 mmHg for the 12/14 F compared to 0 mmHg for the novel UAS. CONCLUSION: The described novel UAS is different from traditional devices by incorporating a syphon mechanism. Our in vitro assessment demonstrates that the novel UAS holds clinical potential to reduce IRP while allowing a significant increase in irrigant flow compared to larger diameter traditional UASs.

Light chain deposition disease presenting as an atrial mass: a case report and review of literature.

Light chain deposition disease (LCDD) also known as nonamyloidotic immunoglobulin deposition disease is a rare systemic disorder due to the abnormal deposition of immunoglobulin in multiple organs caused by the clonal proliferation of B lymphocytes and plasma cells. Renal involvement is the most common with cardiac manifestations being the most common extra renal presentation of the disease. Renal involvement is not always associated with LCDD. Isolated cardiac involvement can manifest in a wide variety of ways: heart failure, cardiomyopathy, arrhythmias, angina, myocardial infarction, etc. We hereby present an unusual case of 59-year-old female who presented to clinic for routine follow up. A murmur on physical exam was evaluated with echocardiogram which led to the discovery of an incidental right atrial mass. Cardiac magnetic resonance imaging was completed 6 months later for follow up which showed increasing size of the mass. The mass was excised and found to be consistent with LCDD. To the best of our knowledge, this is the first reported case of LCDD manifesting as an atrial mass. Through this case report and review of literature we would like to generate awareness among our fellow pathologists and clinicians to maintain a high level of suspicion for LCDD as it can manifest in many unusual ways, with or without kidney involvement.

Florid cystitis cystica et glandularis causing irreversible renal injury.

Cystitis cystica et glandularis (CCEG) is widely believed to be innocuous and self-limiting. We report a case of a 32-year-old male patient who was found to have gross bilateral hydroureter and hydronephrosis and an estimated glomerular filtration rate of 3 ml/min/1.73 m2. Cystoscopy revealed extensive cystic and nodular lesions involving most of the bladder urothelium, which proved to be CCEG on histopathological analysis. Retrograde and anterograde stents could not be inserted due to obstruction of the ureters at the level of the vesicoureteric junction. Percutaneous nephrostomies were subsequently inserted. Although there was evidence of improvement of the CCEG on follow-up cystoscopy, no improvement of renal function, despite decompression with percutaneous nephrostomies, was seen. He was subsequently placed on the waiting list for a renal transplant. We believe this to be the only known case reported of florid CCEG obstructing the upper urinary tracts bilaterally, causing irreversible renal injury.

Prevalence and outcome of sepsis and septic shock in intensive care units in Addis Ababa, Ethiopia: A prospective observational study.

BACKGROUND: Sepsis and septic shock are the major causes of morbidity and mortality in Intensive care Units (ICUs) in low and middle-income countries. However, little is known about their prevalence and outcome in these settings. The study aimed to assess the prevalence and outcome of sepsis and septic shock in ICUs in Addis Ababa, Ethiopia. METHODS: A prospective observational study was conducted from March 2017 to February 2018 in four selected ICUs in Addis Ababa from a total of twelve hospitals having ICU services. There were 1145 total ICU admissions during the study period. All admissions into those ICUs with sepsis, severe sepsis, and septic shock using the Systemic Inflammatory Response Syndrome (SIRS) criteria (SEPSIS-2) during the study period were screened for sepsis or septic shock based on the new sepsis definition (SEPSIS-3). All patients with sepsis and septic shock during ICU admission were included and followed for 28 days of ICU admission. Data analysis was done using the Statistical Package for Social Sciences (SPSS) software version 20.0. RESULTS: A total of 275 patients were diagnosed with sepsis and septic shock. The overall prevalence of sepsis and septic shock was 26.5 per 100 ICU admissions. The most frequent source of sepsis was respiratory infection (53.1%). The median length of stay in the ICUs was 5 (IQR, 2-8) days. The most common bacterium isolate was Pseudomonas aeroginosa (34.5%). The ICU and 28-day mortality rate was 41.8% and 50.9% respectively. Male sex, modified Sequential Organ Failure Assessment score ≥10 on day 1 of ICU admission, and comorbidity of HIV or malignancy were the independent predictors of 28-day mortality. CONCLUSION: Sepsis and septic shock are common among our ICU admissions, and are associated with a high mortality rate.

Current controversies in the management of Graves' hyperthyroidism.

Introduction: The management of Graves' disease centers on the use of effective and well-established therapies, namely thionamide antithyroid drugs, radioactive iodine, and thyroidectomy. Optimal treatment strategies are however controversial and vary significantly across centers.Areas covered: This review addresses specific controversies in Graves' disease management including the choice of primary therapy, the approach to women planning pregnancy, and optimal strategies for antithyroid drug and radioiodine therapy.Expert opinion: Important considerations in choosing therapy include treatment efficacy, adverse effects, patient convenience, and resource settings. Recent data suggest that early and effective control of hyperthyroidism is key to improving cardiovascular morbidity and mortality. Studies addressing cancer risk in radioiodine-treated patients face methodological challenges and require clarification in appropriately designed studies. Remission rates with antithyroid drugs are comparable when thionamides are used alone (titration-regimen) or in combination with levothyroxine (block and replace) and can be optimized by extending treatment for at least 12-18 months. Fixed and calculated radioiodine activity regimens are both effective but entail a trade-off between convenience and precision in the administered activity. Optimal preconception strategies are still evolving but ablative treatment in advance of pregnancy offers the most pragmatic means of reducing adverse effects of hyperthyroidism in subsequent pregnancy.

Decision-Analytic Modeling Studies in Prevention and Treatment of Iodine Deficiency and Thyroid Disorders: A Systematic Overview.

Background: Prevention and treatment of iodine deficiency-related diseases remain an important public health challenge. Iodine deficiency can have severe health consequences, such as cretinism, goiter, or other thyroid disorders, and it has economic implications. Our aim was to give an overview of studies applying decision-analytic modeling to evaluate the effectiveness and/or cost-effectiveness of iodine deficiency-related prevention strategies or treatments related to thyroid disorders. Methods: We performed a systematic literature search in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica Database), Tuft's Cost-Effectiveness Analysis Registry, and National Health System Economic Evaluation Database (NHS EED) to identify studies published between 1985 and 2018 comparing different prevention or treatment strategies for iodine deficiency and thyroid disorders by applying a mathematical decision-analytic model. Studies were required to evaluate patient-relevant health outcomes (e.g., remaining life years, quality-adjusted life years [QALYs]). Results: Overall, we found 3950 studies. After removal of duplicates, abstract/title, and full-text screening, 17 studies were included. Eleven studies evaluated screening programs (mainly newborns and pregnant women), five studies focused on treatment approaches (Graves' disease, toxic thyroid adenoma), and one study was about primary prevention (consequences of iodine supplementation on offspring). Most of the studies were conducted within the U.S. health care context (n = 7). Seven studies were based on a Markov state-transition model, nine studies on a decision tree model, and in one study, an initial decision tree and a long-term Markov state-transition model were combined. The analytic time horizon ranged from 1 year to lifetime. QALYs were evaluated as health outcome measure in 15 of the included studies. In all studies, a cost-effectiveness analysis was performed. None of the models reported a formal model validation. In most cases, the authors of the modeling studies concluded that screening is potentially cost-effective or even cost-saving. The recommendations for treatment approaches were rather heterogeneous and depending on the specific research question, population, and setting. Conclusions: Overall, we predominantly identified decision-analytic modeling studies evaluating specific screening programs or treatment approaches; however, there was no model evaluating primary prevention programs on a population basis. Conclusions deriving from these studies, for example, that prevention is cost-saving, need to be carefully interpreted as they rely on many assumptions.

Renal cortical transit time as a predictor for pyeloplasty in pediatric patients with unilateral hydronephrosis.

Majority of patients with unilateral hydronephrosis (HN) detected on ultrasound do not require pyeloplasty. The measurement of the cortical transit time (CTT) has been demonstrated by several authors to predict the need for patients who may require pyeloplasty. The study aimed to assess if CTT would have predicted a drop in differential renal function (DRF) in patients with unilateral HN on the affected side and to assess whether CTT would differ on the first renogram between those patients who had a pyeloplasty and those who did not have a pyeloplasty. Sixty-eight patients with at least two renograms with unilateral HN with a normal contralateral kidney were observed retrospectively. The CTT was recorded for each kidney. Renograms were processed three times to measure the DRF. The mean of the three DRF measurements was used for analysis. The mean CTT of the left and right hydronephrotic kidneys was 6.0 min and 6.7 min, respectively. The relationship between CTT and DRF as well as CTT and anterior posterior diameter in the first renogram of those patients who did not have a pyeloplasty was statistically significant (P < 0.05). In the 20 patients who had a pyeloplasty, there was a drop of more than 10% in the DRF of three patients. No significant difference was found in CTT or DRF when comparing the group who had surgery against the group who did not have surgery. The current study was unable to demonstrate in our series of patients that CTT can predict a drop in DRF in those patients who would require pyeloplasty.

Validating the European randomised study for screening of prostate cancer (ERSPC) risk calculator in a contemporary South African cohort.

INTRODUCTION: Numerous prostate cancer predictive tools have been developed to help with decision-making in men needing prostate biopsy. However, they have been modelled and validated almost exclusively in Caucasian cohorts, hence limiting their use in other population groups. The aim of this study was to assess the validity of the ERSPC risk calculator in a South African cohort. METHODS: Patients who have had a transrectal ultrasound (TRUS)-guided prostate biopsy at Groote Schuur Hospital from January 2008 to August 2017 were reviewed. Predictor variables were entered into the ERSPC risk calculator and results were compared with prostate biopsy pathology results. Predictive accuracy of the ERSPC risk calculator for these patients was derived using receiver operator characteristics (ROC) Area under the curve and is expressed as a percentage. RESULTS: 516 prostate biopsy sessions in 475 different men were analysed. The predictive accuracy of the ERSPC risk calculator was better than a PSA/DRE strategy for the presence of cancer-0.738 (95% CI 0.695-0.781) vs 0.686 (95% CI 0.639-0.732), and for significant PCa-0.833 (95% CI 0.789-0.876) vs 0.793 (95% CI 0.741-0.846). This translated into 50 less biopsies when compared to a PSA > 4/abnormal DRE strategy. Use of the ERSPC RC would have missed eight non-significant cancers [Significant cancer being defined as having a tumour stage T2b (> 1/2 lobe involved with prostate cancer) and/or a Gleason Score equal to or greater than 7]. CONCLUSION: Our results confirm the validity of the ERSPC RC in a South African cohort. Application of this calculator to the wider South African population would allow better selection of patients for prostate biopsy and spare a significant number its adverse consequences.

Safety of regadenoson positron emission tomography stress testing in orthotopic heart transplant patients.

OBJECTIVES: We sought to determine the safety of regadenoson (REG) stress testing in patients who have undergone orthotopic heart transplantation (OHT). BACKGROUND: Routine screening for cardiac allograft vasculopathy (CAV) is necessary after OHT. Adenosine stress is contraindicated after heart transplantation due to supersensitivity in denervated hearts. Safety of regadenoson stress following OHT has not been well studied. METHODS: We retrospectively reviewed data from OHT patients (N = 123) who were referred to REG stress testing. Medical records were reviewed to determine hemodynamic and ECG response to regadenoson and to identify adverse reactions. RESULTS: No serious adverse events occurred. No life-threatening arrhythmias or hemodynamic changes occurred. Common side-effects related to regadenoson were observed, dyspnea being the most frequent (66.7%). On average the heart rate rose from 82.8 ± 12 to 95.7 ± 13.4 bpm (P < 0.001), systolic blood pressure decreased from 138.7 ± 20.9 to 115.9 ± 23.9 mmHg (P < 0.001) and mean arterial pressure decreased from 103.5 ± 14.1 to 84.72 ± 15.90 mmHg (P < 0.001) during stress protocol. There was no sustained ventricular tachycardia, ventricular fibrillation, or second-or third-degree atrioventricular block. CONCLUSION: Regadenoson stress testing appears to be well tolerated and safe in OHT patients.

Hypothyroidism in Pregnancy.

Thyroid hormone is essential for pregnancy and ensuring fetal development. Pregnancy also places substantial demands on the thyroid axis. Overt hypothyroidism is associated with substantial adverse obstetric and offspring outcomes and requires treatment. Borderline thyroid dysfunction is common in women and associated with adverse obstetric and offspring outcomes, although benefits of screening for and treating borderline thyroid function are unclear. Many women are established on thyroid hormone replacement before pregnancy and doses need increasing during pregnancy. Care is taken to prevent overreplacement. Universal thyroid screening in pregnancy is being undertaken in several countries, although it remains a matter of debate.

Primary therapy of Graves' disease and cardiovascular morbidity and mortality: a linked-record cohort study.

BACKGROUND: Graves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease. METHODS: In this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models. FINDINGS: We extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05-1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29-0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96-2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08-2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality. INTERPRETATION: Regardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone. FUNDING: National Institute for Social Care and Health Research, Wales.

Relationship of non-invasive quantification of myocardial blood flow to arrhythmic events in patients with implantable cardiac defibrillators.

BACKGROUND: Ischemia contributes to arrhythmogenesis though its role is incompletely understood. Abnormal myocardial perfusion measured by PET imaging may predict ventricular arrhythmias (VAs) in a high-risk population. METHODS: Patients with implantable cardiac defibrillators who had undergone rubidium-82 cardiac PET imaging were identified. Patients were stratified by median MBF and MFR values for analysis. The Cox proportional hazards model was used to assess the impact of myocardial perfusion on survival free of VT independent of critical covariates. RESULTS: A total of 159 patients (124 (78%) males, median age 65.9 years, IQR [56.76-72.63]) were followed for 1.43 years IQR [0.83-2.21]. VA occurred in 29 patients (23.7%). After adjustment for ejection fraction, age, and sex, impaired stress MBF was associated with an increased risk of VA (adjusted HR per ml/min/g 1.52, 95% CI (1.01-2.31), P = 0.04). Summed rest and stress scores were not predictive of VA. Among patients with severe LV dysfunction, stress MBF remained an independent predictor of VA (adjusted HR per 1 ml/min/g HR 1.69, 95% CI (1.03-11.36), P = 0.03), while residual EF, summed rest, and summed stress scores were not (P > 0.05). CONCLUSIONS: Impaired stress myocardial blood flow was associated with less survival free of ventricular arrhythmias.

Clear Cell Renal Cell Carcinoma with a Ureteral Thrombus.

Introduction: Cancers of the kidney, arising from either the renal parenchymal tissue or the renal pelvis, is among the 13 commonest types of malignancy globally, accounting for between 3% and 4% of all newly diagnosed cancers. Renal cell carcinoma (RCC) accounts for 85% of all malignant renal neoplasms. We present a rare case of an RCC directly extending into the renal pelvicalyceal system and with a thrombus within the ureter. Case Presentation: A 39-year-old woman presented with a long-standing history of worsening left flank pain, intermittent visible hematuria, and a fullness in the left flank. Apart from an ill-defined left flank mass with pain on palpation, there was nothing remarkable on clinical examination. Contrast-enhanced abdominal CT scan images showed a large, heterogeneously enhancing soft tissue mass arising from the lower pole of the left kidney. The collecting system and the left proximal ureter were poorly visualized. A tentative diagnosis of RCC, cT3aN0M0 was made. Intraoperatively, we identified a large, left lower pole renal mass, displacing the pedicle superiorly. In addition, we found a bulky, dilated proximal ureter. A decision was made intraoperatively to proceed with radical nephrectomy and ureterectomy. Conclusion: We report a rare case of RCC directly invading from the renal pelvis and down the ureter as a thrombus mass, with no microscopic individual tumor implants in the ureter wall, invasion of the renal vein, or invasion of adjacent organs. To our knowledge, only four such cases have been reported in English literature, and as a result, very few theories explaining renal pelvic invasion and direct growth down the ureter have been postulated. This highlights the significance of adding invasion of the pelvicalyceal system as part of the most recent, updated tumor node metastases classification. In future, consideration needs to be given to include the extension of RCC into the ureter and/or bladder.