Search

Hepatocellular carcinoma (HCC) is a major global health problem. Theragnostic is a term that refers to the integration of diagnostic and therapeutic modalities into a single system for personalized medicine. Theragnostic care in HCC involves the use of imaging techniques to diagnose the cancer and assess its characteristics, such as size, location, and extent of spread. Theragnostics involves the use of molecular and genetic tests to identify specific biomarkers that can help guide treatment decisions and, post-treatment, assess the dosimetry and localization of the treatment, thus guiding future treatment. This can be done through either positron emission tomography (PET) scanning or single photon emission tomography (SPECT) using radiolabeled tracers that target specific molecules expressed by HCC cells or radioembolization. This technique can help identify the location and extent of the cancer, as well as provide information on the tumor's metabolic activity and blood supply. In summary, theragnostics is an emerging field that holds promise for improving the diagnosis and treatment of HCC. By combining diagnostic and therapeutic modalities into a single system, theragnostics can help guide personalized treatment decisions and improve patient outcomes. [ABSTRACT FROM AUTHOR]

The area under the ROC curve is frequently used for assessing the predictive efficacy of a model, and the Youden index is commonly used to provide the optimal cut-off. Both are misleading tools for predictions. A ROC curve is drawn for the sensitivity of a quantitative test against its (1 – specificity) at different values of the test. Both sensitivity and specificity are retrospective in nature as these are indicators of correct classification of already known conditions. They are not indicators of future events and are not valid for predictions. Predictivity intimately depends on the prevalence which may be ignored by sensitivity and specificity. We explain this fallacy in detail and illustrate with several examples that the actual predictivity could differ greatly from the ROC curve-based predictivity reported by many authors. The predictive efficacy of a test or a model is best assessed by the percentage correctly predicted in a prospective framework. We propose predictivity-based ROC curves as tools for providing predictivities at varying prevalence in different populations. For optimal cut-off for prediction, in place of the Youden index, we propose a P-index where the sum of positive and negative predictivities is maximum after subtracting 1. To conclude, for correctly assessing adequacy of a prediction models, predictivity-based ROC curves should be used instead of the usual sensitivity-specificity-based ROC curves and the P-index should replace the Youden index. [ABSTRACT FROM AUTHOR]

The incidence and prevalence of neuroendocrine tumours (NETs) are on the rise, but to date, only complete surgical resection is curative. Among the various therapeutic options for metastatic disease, peptide receptor radionuclide therapy (PRRT), linking a radioactive moiety to an octreotide derivative, has been shown to be highly efficacious and a well-tolerated therapy, improving progression-free survival and prolonging overall survival. Nevertheless, complete responses are rare, and the current β-particle emitters have non-optimal radiobiological properties. A new generation of α-particle-emitting radionuclides is being developed, with the advantages of very high energy and a short path length. We survey the most recent developments in this field, summarising the result of currently performed studies in this potentially ground-breaking novel form of therapy for NETs., (© 2024 British Society for Neuroendocrinology.)

Aims: To discuss the role of autocrine/paracrine signaling of urothelial arginine vasopressin (AVP) on mammalian bladder capacities and micturition thresholds, impact of distension on water/urea reabsorption from the bladder, review of the literature to better characterize the central/peripheral effects of AVP, desmopressin (dAVP) toxicity, and urine biomarkers of nocturia., Methods: This review summarizes discussions during an International Consultation on Incontinence-Research Society 2024 think tank with respect to the role of urothelial AVP in aged individuals with nocturnal polyuria, impact of solute and water reabsorption by the bladder on uninterrupted sleep, central effects of AVP, pharmacological basis of dAVP toxicity, and biomarkers in nocturia/lower urinary tract dysfunction (LUTD) with neurological diseases., Results: Consensus recognized AVP function and pathways in the central nervous system (CNS), pre-proAVP localized using immunohistochemistry in bladder sections from adult/aged noncancerous human punch biopsies and rodent bladder sections is likely to accelerate the systemic uptake of water and urea from the bladder of anesthetized mice instilled with 3 H-water and 14 C-urea. Mechanisms for charged and uncharged solutes and water transport across the bladder, mechanism of dAVP toxicity, and utility of urine biomarkers in those with neurological diseases/nocturia were determined from literature reviews., Conclusion: Pre-proAVP is present in human/rodent bladders and may be involved in water reabsorption from bladder that prevents the sensation of fullness for uninterrupted sleep in healthy adults. The mechanism of action of AVP in the CNS was discussed, as was electrolyte/water transport across the bladder, the basis for dAVP toxicity, and feasibility of urine biomarkers to identify nocturia/LUTD with neurological diseases., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Objective: Conventional creatinine-based glomerular filtration rate (GFR) equations have been reported to overestimate renal function in patients with cirrhosis. The Royal Free Hospital (RFH) cirrhosis GFR equation was developed to accurately estimate GFR in this population. The aim of this study was to evaluate the ability of widely available equations [Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), Modification of Diet in Renal Disease equations (MDRD-4, MDRD-6)] and the RFH equation to correctly estimate the GFR of patients with cirrhosis., Methods: We retrospectively analyzed data from patients with cirrhosis who underwent measurement of GFR with the use of 51Cr-EDTA (GFR-M). The CKD-EPI, MDRD-4, MDRD-6 and RFH equations were calculated, while bias, precision and accuracy were estimated for each one of them and then compared with paired t-tests. Bias was defined as the mean difference between the GFR-M and the result of each equation; precision was defined as the SD of the differences and accuracy was defined as the square root of the mean squared error (mean of the squared differences). Higher values are associated with worse bias and better precision/accuracy., Results: One-hundred and thirty-four cirrhotic patients were included. Bias was estimated for CKD-EPI, MDRD-4, MDRD-6 and RFH at -5.91, -3.13, 0.92 and 18.24, respectively. Significant differences were observed between all equations (P < 0.001). Regarding precision, only the comparison between MDRD-4 (20.81) and RFH (16.6) yielded a statistically significant result (P = 0.037). Finally, CKD-EPI (19.32) and MDRD-6 (18.81) exhibited better accuracy than GFR-RFH (24.61) (P = 0.006 and 0.001)., Conclusion: RFH demonstrates inferior accuracy in predicting renal function in patients with cirrhosis, in comparison to conventional equations., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Targeted radionuclide therapy plays an increasingly important role in managing endocrine-related tumors and significantly advances the therapeutic landscape for patients with these diseases. With increasing FDA-approved therapies and advances in the field, come an increased knowledge of the potential for longterm toxicities associated with these therapies and the field must develop new strategies to increase potency and efficacy while individualizing the selection of patients to those most likely to respond to treatment. Novel agents and modalities of therapy are also being explored. This review will discuss the current landscape and describe the avenues for growth in the field currently being explored. [ABSTRACT FROM AUTHOR]

5-hydroxyindole acetic acid, a metabolite of serotonin, is used in the diagnosis and monitoring of patients with neuroendocrine tumours, in particular patients with small intestinal neuroendocrine tumours associated with the carcinoid syndrome. Analysis of 5-hydroxyindole acetic acid was commonly performed in urine, but blood-based assays are now becoming available. The objective of this study was to assess how 5-hydroxyindole acetic acid compares in plasma and serum as a biochemical marker of neuroendocrine tumours. Twenty-four-hour urine, plasma and serum samples were obtained from 80 patients with neuroendocrine tumours and 30 healthy volunteers. We developed a liquid chromatography tandem mass spectrometry assay for plasma and serum 5-hydroxyindole acetic acid. Comparison was made between them, and their cut-off was determined using a receiver-operating characteristic curve. A close correlation was shown between plasma and serum 5-hydroxyindole acetic acid. At a cut-off of 135 nmol/l, a sensitivity of 91.2% with a specificity of 61.9% was obtained for both compared to the urinary assay. A statistically significant agreement was shown when plasma and serum 5-hydroxyindole acetic acid were compared with the currently used urine assay in patients with neuroendocrine tumours; κ = 0.675 (95% CI 0.49 to 0.86), p < 0.001 and healthy volunteers; 0.967 (95% CI 0.828 to 0.999), p = <0.001. In conclusion, 5-hydroxyindole acetic acid in plasma and serum were comparable, hence either sample type can be used interchangeably. [ABSTRACT FROM AUTHOR]

Vesico-ureteric reflux (VUR) into transplanted kidneys in children and young people is a common occurrence, found in 19 to 60% of those who had an anti-reflux procedure and up to 79% in the absence of such a procedure. While VUR is unlikely to be of concern without evidence of symptomatic urinary tract infections, less certainty exists regarding outcomes when the VUR is associated with urinary tract infection (UTI) and transplant pyelonephritis. Issues explored will include additional risk factors that might predispose to UTI, any effect of pyelonephritis on acute and long-term kidney allograft function and practical strategies that may reduce the prevalence of infection. [ABSTRACT FROM AUTHOR]

Purpose: The left ventricular global function index (LVGFI) is a comprehensive marker of cardiac performance, integrating LV morphology with global function. We explored the cross-sectional association of LVGFI with myocardial iron overload (MIO), LV ejection fraction (LVEF), myocardial fibrosis, and heart failure (HF) in β-thalassemia major (TM) patients. Methods: We considered 1352 adult TM patients (708 females, 32.79 ± 7.16years) enrolled in the Myocardial Iron Overload in Thalassemia Network and 112 healthy subjects (50 females, 32.09 ± 6.08years). LVGFI and LVEF were assessed by cine images and MIO by multislice multiecho T2* technique. Replacement myocardial fibrosis was detected by late gadolinium enhancement technique. Results: LVGFI and LVEF were significantly lower in patients with significant MIO (global heart T2*<20ms) than in patients without MIO and in healthy subjects but were comparable between TM patients without MIO and healthy subjects. In TM, LVGFI was significantly associated with LVEF (R = 0.733; p < 0.0001). Global heart T2* values were significantly associated with both LVGFI and LVEF, but the correlation with LVGFI was significantly stronger (p = 0.0001). Male sex, diabetes mellitus, significant MIO, and replacement myocardial fibrosis were the strongest predictors of LVGFI. Eighty-six patients had a history of HF and showed significantly lower global heart T2* values, LVEF, and LVGFI than HF-free patients. A LVGFI ≤ 44.9% predicted the presence of HF. The LVGFI showed a diagnostic performance superior to that of LVEF (area under the curve: 0.67 vs. 0.62; p = 0.039). Conclusion: In TM patients the LVGFI correlates with MIO and provides incremental diagnostic value for HF detection compared with LVEF. [ABSTRACT FROM AUTHOR]

The most attractive features of Auger electrons (AEs) in cancer therapy are their extremely short range and sufficiently high linear energy transfer (LET) for a majority of them. The cytotoxic effects of AE emitters can be realized only in close vicinity to sensitive cellular targets and they are negligible if the emitters are located outside the cell. The nucleus is considered the compartment most sensitive to high LET particles. Therefore, the use of AE emitters could be most useful in specific recognition of a cancer cell and delivery of AE emitters into its nucleus. This review describes the studies aimed at developing effective anticancer agents for the delivery of AE emitters to the nuclei of target cancer cells. The use of peptide-based conjugates, nanoparticles, recombinant proteins, and other constructs for AE emitter targeted intranuclear delivery as well as their advantages and limitations are discussed. Transport from the cytoplasm to the nucleus along with binding to the cancer cell is one of the key stages in the delivery of AE emitters; therefore, several constructs for exploitation of this transport have been developed. The transport is carried out through a nuclear pore complex (NPC) with the use of specific amino acid nuclear localization sequences (NLS) and carrier proteins named importins, which are located in the cytosol. Therefore, the effectiveness of NLS-containing delivery constructs designed to provide energy-dependent transport of AE emitter into the nuclei of cancer cells also depends on their efficient entry into the cytosol of the target cell. [ABSTRACT FROM AUTHOR]

Background: Henoch-Schönlein purpura (HSP) with refractory gastrointestinal (GI) symptoms is always difficult to handle because of its resistance to supportive therapies and glucocorticoid. This study aimed to evaluate the efficacy of hemoperfusion (HP) and intravenous immunoglobulins (IVIG) therapies in this population.Methods: Sixty-four HSP patients with refractory GI involvement (R-GI group) and 64 cases with mild GI symptoms (control group) were retrospectively analyzed in our center from March 2016 to October 2019. In R-GI group, 42 cases (subgroup A) were treated with IVIG and steroid, 13 cases (subgroup B) used HP and steroid, 9 cases (subgroup C) executed a combination of IVIG, HP and steroid. Demographic characteristics, clinical features, laboratory indexes and treatment outcomes were recorded. t-test, One-way ANOVA, Mann-Whitney U test, and multivariate logistic regression were used in comparing differences among subgroups and predicting independent risk factors.Results: Compared with the control group, R-GI cases experienced higher risk of renal involvement (P = 0.000), more steroid exposure (P = 0.000), six times expenses (P = 0.000) and 2.3 times length of hospitalization (P = 0.000). The independent risk factors of R-GI group were elevated neutrophils (OR 1.250 [95% CI 1.130-1.383]) and the percentage of B lymphocytes (OR 1.100 [95% CI 1.026-1.179]) as well as decreased IgG (OR 0.847 [95% CI 0.732-0.98]). In R-GI group, increased age (OR 1.039 [95% CI 1.016-1.062]) and IgM (OR 5.994 [95% CI 1.403-27.611]) were verified to be risk factors of HSP nephritis. All three subgroups could alleviate the symptoms effectively. Compared with those in subgroup A, patients in subgroup B were elder (P = 0.004), had less relapse (P = 0.002), steroid exposure (P = 0.033) and expenses (P = 0.031), more significant decrease of WBC (P = 0.026) after treatment.Conclusion: The HSP with refractory GI involvement had much higher risk of medical burden and renal involvement. Both IVIG and HP therapies could ameliorate refractory GI symptoms efficiently. HP therapy tended to reduce the relapse, costs and steroid exposure in its audiences who were cooperated and with stable hemodynamics, while IVIG had better use in younger children. [ABSTRACT FROM AUTHOR]

Objectives: The impact of vesicoureteral reflux post‐kidney transplantation on graft survival remains unclear, and guidelines on appropriate vesicoureteral reflux management post‐kidney transplantation are lacking. For this reason, we conducted a retrospective study on the impact of vesicoureteral reflux and its treatment on graft survival. Methods: We evaluated 347 consecutive kidney transplantation recipients, who also underwent a ureteroneocystostomy, between 1996 and 2012. Results: Vesicoureteral reflux was diagnosed in 55 cases (15.9%), with a median post‐kidney transplantation duration of 50 months (range 0–172 months). Among these, 22 were monitored, 17 underwent transurethral collagen injections, and 16 received a ureteroneocystostomy. The 10‐year graft survival rate was significantly lower in recipients with vesicoureteral reflux (68.9%) than in those without vesicoureteral reflux (84.4%) (P = 0.0165). Moreover, among the vesicoureteral reflux recipients, the 10‐year graft survival rate was significantly higher in those whose vesicoureteral reflux was cured (80.1%) than in those whose vesicoureteral reflux persisted (53.6%) (P = 0.0062). Multivariate analysis showed that vesicoureteral reflux was significantly associated with both overall and death‐censored graft loss (odds ratio 3.737 and 3.685; P = 0.0015 and P = 0.0052, respectively). Lastly, the incidence of interstitial fibrosis and tubular atrophy was higher in recipients with vesicoureteral reflux than in those without vesicoureteral reflux (P = 0.0009). Conclusions: Post‐kidney transplantation vesicoureteral reflux has a negative impact on long‐term graft survival, and that treatment prevents graft deterioration. From the perspective of maintaining long‐term graft function in kidney recipients, vesicoureteral reflux may be one of the most important complications to be addressed. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary hypertension (CTEPH), defined as precapillary pulmonary hypertension (PH) by right heart catheterization and imaging consistent with chronic thromboembolism, is a long-term complication of pulmonary embolism (PE). Pathobiological mechanisms involve pulmonary artery occlusion from organized thromboembolic material despite at least three months of uninterrupted therapeutic anticoagulation following acute PE and secondary microvasculopathy. Delay in diagnosis and management of CTEPH is associated with poor outcomes. High clinical suspicion, comprehensive assessment of residual dyspnea or exercise intolerance in the aftermath of PE and accurate interpretation of computed tomography pulmonary angiography (CTPA) are pivotal steps in the diagnosis. Ventilation–perfusion (V/Q) scan is the preferred initial radiologic screening tool as normal V/Q essentially rules out CTEPH. Any mismatched perfusion defect on the V/Q scan in the setting of PH or any finding compatible with chronic thromboembolism on CTPA should prompt referral to an expert CTEPH center. Once the diagnosis is verified, all eligible patients should be offered pulmonary thromboendarterectomy (PTE). Pulmonary vasodilators or balloon pulmonary angioplasty are safe and effective in inoperable or post-PTE persistent/recurrent CTEPH. During the course of their disease, a patient may receive a combination of treatments, at times consisting of all three strategies. Lifelong therapeutic anticoagulation is recommended for CTEPH. [ABSTRACT FROM AUTHOR]

The treatment options that are currently available for management of metastatic, progressive radioactive iodine (RAI)-refractory differentiated thyroid cancers (DTCs), and medullary thyroid cancers (MTCs) are limited. While there are several systemic targeted therapies, such as tyrosine kinase inhibitors, that are being evaluated and implemented in the treatment of these cancers, such therapies are associated with serious, sometimes life-threatening, adverse events. Peptide receptor radionuclide therapy (PRRT) has the potential to be an effective and safe modality for treating patients with somatostatin receptor (SSTR)+ RAI-refractory DTCs and MTCs. MTCs and certain sub-types of RAI-refractory DTCs, such as Hürthle cell cancers which are less responsive to conventional modalities of treatment, have demonstrated a favorable response to treatment with PRRT. While the current literature offers hope for utilization of PRRT in thyroid cancer, several areas of this field remain to be investigated further, especially head-to-head comparisons with other systemic targeted therapies. In this review, we provide a comprehensive outlook on the current translational and clinical data on the use of various PRRTs, including diagnostic utility of somatostatin analogs, theranostic properties of PRRT, and the potential areas for future research. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Reconstructive Urology is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Studies comparing the modified Schwartz formula with measured GFR (m-GFR) are lacking in critically ill children. Methods: This prospective cohort study enrolled children aged 1 month to 12 years, within 24 h of admission. m-GFR measured by technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) and calculated by Russell's two-sample slope-intercept method. Serum creatinine was estimated by modified Jaffe method and estimated GFR (e-GFR) calculated by modified Schwartz formula. The primary outcome was to find agreement between the two methods. Bias, precision, and accuracy were calculated. Secondary outcomes were the incidence of AKI (by p-RIFLE criteria) and the difference between the two methods to diagnose AKI. Results: A total of 208 pairs were analyzed. e-GFR showed good agreement with m-GFR with a mean bias of –4.37 ml/min/1.73 m2 and precision (SD of bias) of 33.07, 95% limit of agreement –69.18 to 60.45, and intraclass correlation of 74% (95%CI 66–80%, P < 0.001). e-GFR underestimated m-GFR by 19.8% (95% CI 7.9–31.7%). Accuracy of e-GFR values within 10%, 20%, and 30% of m-GFR were 68.3%, 72.6%, and 78.8%, respectively. Incidence of AKI within 24 h was 60.1% by e-GFR and 54.3% by m-GFR (kappa 0.569, P < 0.001; sensitivity of 85.8%, 95%CI (78–91.7%). Conclusions: The modified Schwartz formula shows good agreement with 99mTc-labeled DTPA double plasma sample clearance method for calculating GFR in critically ill children aged 1 month to 12 years. The underestimation of GFR should be kept in mind while applying the formula at the bedside in PICU. Trial registration: Protocol accessible at Clinical Trial Registry of India (CTRI) www.ctri.nic.in. (Trial Registered Prospectively and Registration No. CTRI/2017/10/010014) ([Registered on: 06/10/2017] Trial Registered Prospectively.) (Title "Measured glomerular filtration rate using Diethylenetriaminepentaacetic acid (DTPA) renal scan versus estimated glomerular filtration rate using modified Schwartz formula in critically ill children: A prospective observational, analytical study."). [ABSTRACT FROM AUTHOR]

Background: While Urinary tract infections are the most common infections in kidney transplant recipients, the impact of late acute graft pyelonephritis (AGPN) on graft outcomes remains unknown. Our study was performed to more precisely evaluate the long-term impact of AGPN. Methods: We included 9052 kidney and combined kidney-pancreas recipients who underwent transplantation between 2008 and 2018 from a French multicenter cohort. The relationships between AGPN and patient and graft survival were analyzed with a time-dependent multivariate Cox model. Results: The cumulative incidence of AGPN was 20.9%. A first episode of early AGPN is associated with a non-significant increase in the risk of graft failure (hazard ratio [HR], 1.27; 95% confidence interval [95% CI], 0.90 to 1.79). Though, cumulative number of AGPN episodes (HR = 1.51; 95% CI, 0.89 to 2.57 for two episodes and HR = 2.08; 95% CI, 1.17 to 3.69 for three or more episodes) is associated with an increased risk of graft failure. In contrast, when the first episode of AGPN occurred late (i.e., 6 months post transplantation), the risk of graft failure is significantly increased (HR = 2.25; 95% CI, 1.65 to 3.07), and this risk remains relatively stable with the recurrence of late AGPN episodes. The onset of late AGPN were also associated with a higher risk of patient death. Conclusion: This analysis shows that late AGPN and recurrent AGPN are both risk factors for a poor long-term graft outcome and mortality. Late AGPN should not be considered benign infections in post-transplantation follow-up. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors are a heterogeneous group of tumors with a wide range of malignant potential that tend to have a relative prolonged course. These tumors infrequently metastasize to the orbit. To the best of our knowledge, ocular metastases from pancreatic neuroendocrine tumors (PNETs) have never been reported in the literature. We report the case of a 61‐year‐old man who presented with progressive deterioration of general condition with unilateral recurrent episodes of non‐granulomatous panuveitis of the left eye related to a choroidal metastasis. Radiological imaging and histopathological analyses led to the diagnosis of metastatic pancreatic neuroendocrine carcinoma as the primary tumor. Choroidal metastases from neuroendocrine tumors are extremely rare, but compromise patients' well‐being because of visual impairment. Uncommonly, these metastases can be the first manifestation of unknown tumors, warranting further investigations to detect the primary cancer. [ABSTRACT FROM AUTHOR]

Context: Targeting MUC1 antigens which are overexpressed in 80% of breast cancers can be widely used in the field of radioimmunoscintigraphy (RIS) of breast cancer.Aims: The aim of this study was to develop a new diagnostic labeled compound for breast cancer RIS.Settings and Design: In this study, an efficient indirect labeling method of PR81 with Indium-111 was developed and preliminary preclinical qualifications were reported.Subjects and Methods: 111In-DTPA-PR81 was prepared and its radiochemical purity and stabilities in human serum and in phosphate-buffered saline (PBS) buffer were surveyed. Furthermore, cellular studies including complex reactivity, binding specificity, cell toxicity, etc., were examined. Finally, biodistribution and scintigraphy of the complex were studied in normal and tumoral animals.Statistical Analysis Used: Statistical analyses were performed using SPSS 10.0.Results: 111In-DTPA-PR81 was prepared with a radiochemical purity of >99% at optimized conditions. Stability studies showed the radiochemical purity of >90% in PBS buffer after 96 h, while the stability in human serum showed decrement to 81% after 96 h. Reactivity of the complex with MUC1 was significantly (P < 0.005) higher than bovine serum albumin (BSA) (about 7-8 times), even though BSA concentration was about twice the MUC1. The binding specificity of the complex to the MUC1 antigen was confirmed by means of immunoreactivity assay. Cell toxicity examination showed no significant lethal effect of the radiolabeled compound on the cells. Biodistribution studies of the complex in normal rats were consistent with the biodistribution of antibodies and high accumulation was observed in the tissues expressing MUC1 antigen. The results of 111In-DTPA-PR81 scintigraphy in tumoral female BALB/c mice at 24 and 48 h after injection showed an increasement of the accumulation in the tumor site.Conclusions: 111In-DTPA-PR81 can be considered as a potential agent for imaging of the MUC1 +breast tumors. [ABSTRACT FROM AUTHOR]

Objective: Given the rarity of refractory pheochromocytoma and paraganglioma (PPGL), outcomes and prognostic factors after 131I-metaiodobenzylguanidine (131I-mIBG) treatment still remain unclear. Therefore, this study evaluated whether baseline characteristics at initial 131I-mIBG therapy and imaging response to repeated 131I-mIBG therapy could be prognostic factors for refractory PPGL. Methods: All patients [n = 59 (male/female = 35/24), median age; 49.3 years] with refractory PPGL who received 131I-mIBG therapy at our institution between September 2009 and September 2019 were retrospectively reviewed for the effects of the following factors on overall survival: age, sex, hypertension, diabetes mellitus, palpitations, constipation, cancer pain, catecholamines values, past history of therapy (external beam radiation for bone metastasis, operation, and chemotherapy), metastasis sites, and response to 131I-mIBG treatments. Results: Throughout the follow-up period, 18 patients died from disease exacerbation. The estimated 5- and 10-year survival rates were 79.4% and 67.2% from the initial diagnoses of refractory PPGL and 68.5% and 49.9% from the first 131I-mIBG therapy, respectively. The multivariate Cox proportional hazards model showed that progressive disease (PD) [hazard ratio (HR) 96.3, P = 0.011] and constipation (HR 8.2, P = 0.024) were adverse prognostic factors for overall survival after initial 131I-mIBG therapy. The log-rank test demonstrated that PD in response to 131I-mIBG therapies (P < 0.0001) and constipation (P < 0.01) were correlated with poor survival rates. Conclusions: Response to repeated 131I-mIBG treatment can be a strong predictor of prognosis after initial 131I-mIBG therapy for refractory PPGL. Repeated 131I-mIBG therapy may be a good option for controlling refractory PPGL. [ABSTRACT FROM AUTHOR]

Purpose: Renal scintigraphy (RS) with either technetium-99 m diethylene-triamine-pentaacetate (Tc-99 m DTPA) or technetium-99 m mercaptoacetyltriglycine (Tc-99 m MAG3) has both been used to evaluate early allograft function after kidney transplantation (KT). This study was done to compare the predictive performance of RS using these two radiopharmaceuticals for prediction of outcomes during first 3 months of KT. Methods: This retrospective study included patients who received KT then underwent both Tc-99 m DTPA and Tc-99 m MAG3 RS, successively. Receiver operating characteristic (ROC) curve analysis was used to determine the predictiveness of RS parameters on early clinical adverse outcomes of either (1) graft-related death, (2) need for graft resection, (3) delayed graft function requiring temporary dialysis, or (4) a serum creatinine level of ≥ 2.0 mg/dL at three months post-KT, as well as to predict biopsy-confirmed acute tubular necrosis and acute rejection. Results: Of 187 patients included, 77 (41.2%) had at least one early adverse clinical outcome. Tc-99 m MAG3 RS was more predictive than Tc-99 m DTPA RS, in terms of AUCROC, in three parameters including time to peak (0.754 vs. 0.516, p-value 0.0001), 20-min to peak ratio (0.762 vs. 0.651, p-value 0.006), and 20-min to 3-min ratio (0.823 vs. 0.699, p-value 0.0005). Acute tubular necrosis was better predicted by Tc-99 m MAG3 RS while both were at best only modest in predicting acute rejection. Conclusion: Three parameters which, when obtained from Tc-99 m MAG3 RS, had superior predictiveness compared with Tc-99 m DTPA RS, including time to peak, 20-min to peak ratio, and 20-min to 3-min ratio. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Tepecik Education & Research Hospital / İzmir Tepecik Eğitim ve Araştırma Hastanesi Dergisi is the property of Logos Medical Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article provides an overview of the diagnosis and the treatment of lower urinary tract symptoms in older adults complicated by the neurodegenerative changes in the micturition reflex and further confounded by age-related decline in hepatic and renal clearance raising the propensity of adverse drug reactions. The first-line drug treatment for lower urinary tract symptoms, orally administered antimuscarinics, fails to reach the equilibrium dissociation constant of muscarinic receptors even at their maximum plasma concentration and tends to evoke a half-maximal response at a muscarinic receptor occupancy of just 0.206% in the bladder with a minimal difference from exocrine glands, which raises the adverse drug reaction risk. On the contrary, intravesical antimuscarinics are instilled at concentrations 1000-fold higher than the oral maximum plasma concentration and the equilibrium dissociation constant erects a downhill concentration gradient that drives passive diffusion and achieves a mucosal concentration around ten-fold lower than the instilled concentration for a long-lasting occupation of muscarinic receptors in mucosa and sensory nerves. A high local concentration of antimuscarinics in the bladder triggers alternative mechanisms of action and is supposed to engage retrograde transport to nerve cell bodies for neuroplastic changes that underlie a long-lasting therapeutic effect, while an intrinsically lower systemic uptake of the intravesical route lowers the muscarinic receptor occupancy of exocrine glands to lower the adverse drug reaction relative to the oral route. Thus, the traditional pharmacokinetics and pharmacodynamics of oral treatment are upended by intravesical antimuscarinics to generate a dramatic improvement (~ 76%) noted in a meta-analysis of studies enrolling children with neurogenic lower urinary tract symptoms on the primary endpoint of maximum cystometric bladder capacity as well as the secondary endpoints of filling compliance and uninhibited detrusor contractions. The therapeutic success of intravesical multidose oxybutynin solution or oxybutynin entrapped in the polymer for sustained release in the pediatric population bodes well for patients with lower urinary tract symptoms at the other extreme of the age spectrum. Though generally used to predict oral drug absorption, Lipinski's rule of five can also explain the ten-fold lower systemic uptake from the bladder of positively charged trospium over oxybutynin, a tertiary amine. Chemodenervation by an intradetrusor injection of onabotulinumtoxinA is merited for patients with idiopathic overactive bladder discontinuing oral treatment because of a lack of efficacy. However, age-related peripheral neurodegeneration potentiates the adverse drug reaction risk of urinary retention that motivates the quest of liquid instillation, delivering larger fraction of onabotulinumtoxinA to the mucosa as opposed to muscle by an intradetrusor injection can also probe the neurogenic and myogenic predominance of idiopathic overactive bladder. Overall, the treatment paradigm of lower urinary tract symptoms in older adults should be tailored to individual's overall health status and the risk tolerance for adverse drug reactions., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Recurrent urinary tract infections (UTIs) after kidney transplantation are a common problem adversely affecting graft outcomes. This retrospective study aimed to report the frequency and risk factors of recurrent UTI and their impact on graft and patient outcomes in kidney transplant recipients at the Sindh Institute of Urology and Transplantation, Karachi, Pakistan, in January-December 2015. Five-year graft and patient survival rates were compared among different groups using Kaplan-Meier analysis. Of the 251 recipients, 67 developed one episode of UTI. Of these 67, 29 had 76 episodes of recurrent UTI. Out of the 76 episodes of recurrent UTI, Escherichia coli was the most common pathogen in 32 cases. Organisms causing recurrent UTI showed resistance to carbapenem in 19 cases versus 2 in the non-recurrent UTI group (P = 0.006). The estimated glomerular filtration rate at 1 year was 57.8 ± 16.23 mL/min/1.73 m2 in the recurrent UTI group vs. 61.9 ± 15.7 mL/min/1.73 m2 in the non-recurrent UTI group (P = 0.001). Graft survival in the recurrent UTI group at 5 years was significantly lower (76%) than in the non-recurrent UTI (95%) and no UTI groups (93%) (log-rank P = 0.006), with no significant effect on patient survival in these groups (P = 0.429). The presence of double-J stent (P = 0.036) and cytomegalovirus infections (P = 0.013) independently predicted recurrent UTI. Recurrent UTIs are common in low-resource settings and adversely affect graft outcomes. Appropriate prophylaxis and treatment are important to reduce recurrent UTI to improve graft outcomes., (Copyright © 2022 Copyright: © 2022 Saudi Journal of Kidney Diseases and Transplantation.)

Abstract: A 99mTc-sestamibi parathyroid scintigraphy was performed in a 27-year-old woman to evaluate possible hyperparathyroidism. The images did not identify any parathyroid abnormality. However, an intense activity was noted in the proximal left upper extremity, which was confirmed as giant cell tumor of the proximal left humerus by pathological examination., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Studies comparing the modified Schwartz formula with measured GFR (m-GFR) are lacking in critically ill children., Methods: This prospective cohort study enrolled children aged 1 month to 12 years, within 24 h of admission. m-GFR measured by technetium-99m-labeled diethylenetriaminepentaacetic acid ( 99m Tc-DTPA) and calculated by Russell's two-sample slope-intercept method. Serum creatinine was estimated by modified Jaffe method and estimated GFR (e-GFR) calculated by modified Schwartz formula. The primary outcome was to find agreement between the two methods. Bias, precision, and accuracy were calculated. Secondary outcomes were the incidence of AKI (by p-RIFLE criteria) and the difference between the two methods to diagnose AKI., Results: A total of 208 pairs were analyzed. e-GFR showed good agreement with m-GFR with a mean bias of -4.37 ml/min/1.73 m 2 and precision (SD of bias) of 33.07, 95% limit of agreement -69.18 to 60.45, and intraclass correlation of 74% (95%CI 66-80%, P < 0.001). e-GFR underestimated m-GFR by 19.8% (95% CI 7.9-31.7%). Accuracy of e-GFR values within 10%, 20%, and 30% of m-GFR were 68.3%, 72.6%, and 78.8%, respectively. Incidence of AKI within 24 h was 60.1% by e-GFR and 54.3% by m-GFR (kappa 0.569, P < 0.001; sensitivity of 85.8%, 95%CI (78-91.7%)., Conclusions: The modified Schwartz formula shows good agreement with 99m Tc-labeled DTPA double plasma sample clearance method for calculating GFR in critically ill children aged 1 month to 12 years. The underestimation of GFR should be kept in mind while applying the formula at the bedside in PICU., Trial Registration: Protocol accessible at Clinical Trial Registry of India (CTRI) www.ctri.nic.in . (Trial Registered Prospectively and Registration No. CTRI/2017/10/010014) ([Registered on: 06/10/2017] Trial Registered Prospectively.) (Title "Measured glomerular filtration rate using Diethylenetriaminepentaacetic acid (DTPA) renal scan versus estimated glomerular filtration rate using modified Schwartz formula in critically ill children: A prospective observational, analytical study."). A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2021. IPNA.)

Objective: Given the rarity of refractory pheochromocytoma and paraganglioma (PPGL), outcomes and prognostic factors after 131 I-metaiodobenzylguanidine ( 131 I-mIBG) treatment still remain unclear. Therefore, this study evaluated whether baseline characteristics at initial 131 I-mIBG therapy and imaging response to repeated 131 I-mIBG therapy could be prognostic factors for refractory PPGL., Methods: All patients [n = 59 (male/female = 35/24), median age; 49.3 years] with refractory PPGL who received 131 I-mIBG therapy at our institution between September 2009 and September 2019 were retrospectively reviewed for the effects of the following factors on overall survival: age, sex, hypertension, diabetes mellitus, palpitations, constipation, cancer pain, catecholamines values, past history of therapy (external beam radiation for bone metastasis, operation, and chemotherapy), metastasis sites, and response to 131 I-mIBG treatments., Results: Throughout the follow-up period, 18 patients died from disease exacerbation. The estimated 5- and 10-year survival rates were 79.4% and 67.2% from the initial diagnoses of refractory PPGL and 68.5% and 49.9% from the first 131 I-mIBG therapy, respectively. The multivariate Cox proportional hazards model showed that progressive disease (PD) [hazard ratio (HR) 96.3, P = 0.011] and constipation (HR 8.2, P = 0.024) were adverse prognostic factors for overall survival after initial 131 I-mIBG therapy. The log-rank test demonstrated that PD in response to 131 I-mIBG therapies (P < 0.0001) and constipation (P < 0.01) were correlated with poor survival rates., Conclusions: Response to repeated 131 I-mIBG treatment can be a strong predictor of prognosis after initial 131 I-mIBG therapy for refractory PPGL. Repeated 131 I-mIBG therapy may be a good option for controlling refractory PPGL., (© 2021. The Japanese Society of Nuclear Medicine.)