Consensus statement addressing controversies and guidelines on pediatric urolithiasis.

PURPOSE: We aimed to investigate controversial pediatric urolithiasis issues systematically, integrating expert consensus and comprehensive guidelines reviews. METHODS: Two semi-structured online focus group meetings were conducted to discuss the study's need and content, review current literature, and prepare the initial survey. Data were collected through surveys and focus group discussions. Existing guidelines were reviewed, and a second survey was conducted using the Delphi method to validate findings and facilitate consensus. The primary outcome measures investigated controversial issues, integrating expert consensus and guideline reviews. RESULTS: Experts from 15 countries participated, including 20 with 16+ years of experience, 2 with 11-15 years, and 4 with 6-10 years. The initial survey identified nine main themes, emphasizing the need for standardized diagnostic and treatment protocols and tailored treatments. Inter-rater reliability was high, with controversies in treatment approaches (score 4.6, 92% agreement), follow-up protocols (score 4.8, 100% agreement), and diagnostic criteria (score 4.6, 92% agreement). The second survey underscored the critical need for consensus on identification, diagnostic criteria (score 4.6, 92% agreement), and standardized follow-up protocols (score 4.8, 100% agreement). CONCLUSION: The importance of personalized treatment in pediatric urolithiasis is clear. Prioritizing low-radiation diagnostic tools, effectively managing residual stone fragments, and standardized follow-up protocols are crucial for improving patient outcomes. Integrating new technologies while ensuring safety and reliability is also essential. Harmonizing guidelines across regions can provide consistent and effective management. Future efforts should focus on collaborative research, specialized training, and the integration of new technologies in treatment protocols.

Fate of Quasiparticles at High Temperature in the Correlated Metal Sr_{2}RuO_{4}.

We study the temperature evolution of quasiparticles in the correlated metal Sr_{2}RuO_{4}. Our angle resolved photoemission data show that quasiparticles persist up to temperatures above 200 K, far beyond the Fermi liquid regime. Extracting the quasiparticle self-energy, we demonstrate that the quasiparticle residue Z increases with increasing temperature. Quasiparticles eventually disappear on approaching the bad metal state of Sr_{2}RuO_{4} not by losing weight but via excessive broadening from super-Planckian scattering. We further show that the Fermi surface of Sr_{2}RuO_{4}-defined as the loci where the spectral function peaks-deflates with increasing temperature. These findings are in semiquantitative agreement with dynamical mean field theory calculations.

Distinct nitrogen isotopic compositions of healthy and cancerous tissue in mice brain and head&neck micro-biopsies.

BACKGROUND: Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio (15N/14N), its recycling may cause cancer tissue to have lower 15N/14N than surrounding healthy tissue. We investigated whether, within a given tissue type in individual mice, tumoral and healthy tissues could be distinguished based on their 15N/14N. METHODS: Micro-biopsies of murine tumors and adjacent tissues were analyzed for 15N/14N using novel high-sensitivity methods. Isotopic analysis was pursued in Nude and C57BL/6 mice models with mature orthotopic brain and head&neck tumors generated by implantation of H454 and MEERL95 murine cells, respectively. RESULTS: In the 7 mice analyzed, the brain tumors had distinctly lower 15N/14N than healthy neural tissue. In the 5 mice with head&neck tumors, the difference was smaller and more variable. This was at least partly due to infiltration of healthy head&neck tissue by tumor cells. However, it may also indicate that the 15N/14N difference between tumoral and healthy tissue depends on the nitrogen metabolism of the healthy organ in question. CONCLUSIONS: The findings, coupled with the high sensitivity of the 15N/14N measurement method used here, suggest a new approach for micro-biopsy-based diagnosis of malignancy as well as an avenue for investigation of cancer metabolism.

Superior Sensitivity of Ex Vivo IFN-γ Release Assays as Compared to Skin Testing in Immunocompromised Patients.

Comparative assessment of the tuberculin skin testing (TST) and commercial IFN-γ release-assays (IGRAs) is hampered by the use of different antigens (tuberculin PPD in TST vs. ESAT-6/CFP-10 in IGRAs). Thus, PPD was used as a common stimulus to compare performance of the TST and three IGRAs in 72 controls, 101 hemodialysis patients and 100 renal transplant recipients. Results of the TST were compared with PPD-induced IFN-γ induction in vitro detected by ELISPOT, ELISA or a flow-cytometric FACS assay. Percentages of positive tests were significantly lower in TST (9.2%) compared to ELISA (55.3%), ELISPOT (45.3%) and FACS (44.9%, p < 0.0001). Agreement between TST and IGRAs was highest for controls (κ = 0.19-0.32) and poor in immunocompromised patients (κ = 0 for transplant patients, κ = 0.06-0.13 for hemodialysis patients). Discrepant results were largely TST negative and IGRA positive. Among IGRAs, agreement was highest between ELISPOT and FACS (κ = 0.61). Unlike TST, all IGRAs were associated with variables of mycobacterial exposure. Among IGRAs, the FACS assay was least affected by the level of immunosuppression. In conclusion, both the percentage of positive results and between-test-agreement were higher with IGRAs as compared to TST. This indicates superiority of IGRAs in detecting a PPD-specific immune response which may also apply for immunity toward Mycobacterium tuberculosis-specific antigens.

Intravitreal dexamethasone implant versus anti-VEGF injection for treatment-naïve patients with retinal vein occlusion and macular edema: a 12-month follow-up study.

PURPOSE: The objective of his study was to compare the visual and anatomical outcomes in treatment-naïve patients with macular edema secondary to retinal vein occlusion after intravitreal injections of dexamethasone implants (DEX) and anti-VEGF. METHODS: One hundred two patients (64 in the anti-VEGF group, 38 in the DEX group) without previous treatment were included in this multi-center retrospective study and evaluated at baseline and 1, 3, 6, and 12 months after the onset of treatment. Patients were defined as "good responders" if central macular thickness (CMT) was less than or equal to 250 µm in TD-OCT or 300 µm in SD-OCT after the injections. RESULTS: At month 3 (n = 102), BCVA had increased significantly, by 0.1 ± 0.3 logMAR in the anti-VEGF group (p = 0.04) and 0.4 ± 0.4 logMAR in the DEX group (p < 0.001); the difference between the two groups was statistically significant (p = 0.007). CMT decreased significantly, by 138 ± 201 µm (-19 %, p < 0.001) in the anti-VEGF group and 163 ± 243 µm (-21 %, p < 0.001) in the DEX group. After 3 months, five patients (13 %) in the DEX group and 20 (31 %) in the anti-VEGF group (p < 0.001) changed treatment. Among the 77 patients who did not switch from their initial treatment, no significant functional or anatomical difference between the two groups was observed at months 6 and 12. Elevation of intraocular pressure > 21 mmHg was more frequent in the DEX group (21 %) than in the anti-VEGF group (3 %, p = 0.008). CONCLUSIONS: Visual acuity recovery was better in the DEX group than in the anti-VEGF group at month 3, but with no difference in CMT. In patients who did not change treatment, the long-term anatomical and visual outcome was similar between the DEX and anti-VEGF groups.

KDEL-cargo regulates interactions between proteins involved in COPI vesicle traffic: measurements in living cells using FRET.

How the occupied KDEL receptor ERD2 is sorted into COPI vesicles for Golgi-to-ER transport is largely unknown. Here, interactions between proteins of the COPI transport machinery occurring during a "wave" of transport of a KDEL ligand were studied in living cells. FRET between CFP and YFP fusion proteins was measured by multifocal multiphoton microscopy and bulk-cell spectrofluorimetry. Ligand binding induces oligomerization of ERD2 and recruitment of ARFGAP to the Golgi, where the (ERD2)n/ARFGAP complex interacts with membrane-bound ARF1. During KDEL ligand transport, interactions of ERD2 with beta-COP and p23 decrease and the proteins segregate. Both p24a and p23 interact with ARF1, but only p24 interacts with ARFGAP. These findings suggest a model for how cargo-induced oligomerization of ERD2 regulates its sorting into COPI-coated buds.

[Update of the 2Sk guidelines on the diagnostics, treatment and metaphylaxis of urolithiasis (AWMF register number 043-025) : What is new?] / Aktualisierung der S2k-Leitlinie zur Diagnostik, Therapie und Metaphylaxe der Urolithiasis (AWMF Registernummer 043-025) : Was ist neu?

The increase of medical knowledge and technical innovations together with the demographic change represent a challenge for the new conception of guidelines and clinical studies. The present S2k guidelines, which are exclusively concerned with kidney and ureteral stones, should support the treatment of urolithiasis in hospitals and private practices and provide information on urolithiasis for patients. Increasing interdisciplinary collaboration in stone treatment is also demonstrated in the number of professional and working groups participating in the update of the new guidelines. The present S2k guidelines emerged from a consensus process and demonstrate the current recommendations in step with actual practice. They provide decision-making guidance for diagnostics, treatment and metaphylactic measures based on expert opinions and available published fundamental evidence from the literature.

Homoleptic U(iii) and U(iv) amidate complexes.

The syntheses of the first homoleptic U(iii) and U(iv) amidate complexes are described. These can be interconverted by chemical reduction/oxidation, showing an unusual change in coordination number from four in the U(iii) complex to eight in the U(iv) complex in the solid state structures.

Blocking extracellular activation of myostatin as a strategy for treating muscle wasting.

Many growth factors are intimately bound to the extracellular matrix, with regulated processing and release leading to cellular stimulation. Myostatin and GDF11 are closely related members of the TGFß family whose activation requires two proteolytic cleavages to release the growth factor from the prodomain. Specific modulation of myostatin and GDF11 activity by targeting growth factor-receptor interactions has traditionally been challenging. Here we demonstrate that a novel strategy for blocking myostatin and GDF11, inhibition of growth factor release, specifically and potently inhibits signaling both in vitro and in vivo. We developed human monoclonal antibodies that selectively bind the myostatin and GDF11 precursor forms, including a subset that inhibit myostatin proteolytic activation and prevent muscle atrophy in vivo. The most potent myostatin activation-blocking antibodies promoted robust muscle growth and resulted in significant gains in muscle performance in healthy mice. Altogether, we show that blocking the extracellular activation of growth factors is a potent method for preventing signaling, serving as proof of concept for a novel therapeutic strategy that can be applied to other members of the TGFß family of growth factors.

[What kind of stone prevention for whom? Risk-adjusted metaphylaxis following urinary stone disease]. / Welche Metaphylaxemassnahme für wen? Ein Konzept zur Risikoadaptierten Harnsteinmetaphylaxe.

Approximately 5% of the German population suffers from urinary stone disease, but only 25% of these urolithiasis patients are at risk of recurrent stone disease or a severe metabolic disorder. It is important that patients at high risk are picked up early, so that appropriate therapy and measures designed to prevent secondary stone disease can be implemented. Risk classification is easily achieved by combining stone analysis with a basic diagnostic program. Patients at low risk need no further diagnostic evaluation or treatment, so that it is enough to recommend general metaphylaxis in these cases. In contrast, patients at high risk require additional specific aftercare and should be evaluated with the aid of a comprehensive diagnostic program from the start to allow precise definition of the metabolic targets.

[Evidence-based pharmacological metaphylaxis of stone disease]. / Evidenzbasierte Pharmakologische Harnsteinmetaphylaxe.

Approximately one-fourth of urolithiasis patients are at high risk for recurrent stone formation or severe metabolic disturbances. These patients need specific metaphylaxis for effective stone prevention, adjusted to their individual metabolic risk. Recent recommendations for the pharmacological treatment of stone diseases are summarized in this article. For the different treatment options, evidence from the literature was assessed. In addition, a follow-up concept for pharmacologically treated high-risk stone formers is discussed.

Standard principles for preventing and controlling infection.

Infection control is a priority for all nurses and healthcare staff. This article examines factors contributing to current healthcare-associated infection rates and outlines the main strategies for infection prevention, management and control.

[The most important current guideline recommendations on the topic urolithiasis : A brief comparison]. / Die wichtigsten aktuellen Leitlinienempfehlungen zum Thema Urolithiasis : Ein kurzer Vergleich.

For the development of patient-specific therapies the guidelines offer the physician a valuable catalogue of possible treatment options. They are based on the current level of knowledge and urological research, but also let some space for individual treatment at the same time. In this article, the current guidelines of several urological associations on the topic of urolithiasis regarding recommendations are described and the differences are highlighted.

[Sympathetic ophthalmia : Therapy with steroid-free immunosuppressant azathioprine]. / Sympathische Ophthalmie : Therapie mit steroidsparendem Immunsuppressivum Azathioprin.

This article describes the case of a 48-year-old male patient who presented with persistent inflammation and deterioration of vision to a best corrected visual acuity (BCVA) of 0.6 in the only functioning left eye. The right eye had suffered a severe penetrating ocular trauma 6 months prior to presentation. After diagnosis of a sympathetic ophthalmia a high dosage corticosteroid therapy was initiated. Due to intolerance with decompensating diabetes an immunosuppressive therapy with azathioprine was initiated. This therapy resulted in stable clinical findings with an increase in BCVA to 0.9.

[Calcium oxalate stones and hyperoxaluria. What is certain? What is new?]. / Kalciumoxalatharnsteine und Hyperoxalurie. Was ist gesichert? Was ist neu?

Approximately 4 million Germans suffer from stone disease. In the majority of cases (70-75%) it is calcium oxalate. Its pathophysiology is complex and comprises disorders such as hypercalciuria, hyperoxaluria, hypocitraturia, hyperuricosuria, and hypomagnesuria. These biochemical changes in urine are well known as "classic" risk factors of calcium oxalate stone formation. However, studies in the last decade showed that calcium oxalate stones are strongly related with other diseases or disorders such as overweight, hypertension, or a lack of oxalate-degrading bacteria in the gut. The evidence for these "new" risk factors in the literature is very strong. It is particularly important in regard to effective treatment and aftercare of patients with calcium oxalate stones to be familiar with both the "classic" and the new risk factors.

[Innovative concepts in early cancer detection and staging of localized prostate cancer]. / Innovative Diagnostik in der Früherkennung und beim Staging des lokalisierten Prostatakarzinoms.

Prostate cancer is the most common malignancy in males. Men aged 50 years and older are recommended to undergo an annual digital rectal examination (DRE) and determination of prostate-specific antigen (PSA) in serum for early detection. Fortunately, disease-specific mortality continues to decline as a result of advances in screening, staging, and patient awareness. However, about 30% of men with a clinically organ-confined disease show evidence of extracapsular extension or seminal vesicle invasion on pathological analysis. Consequently, there is a need for more accurate diagnostic tools for planning tailored treatment. A variety of modern imaging techniques has been implemented in an attempt to obtain more precise staging, thereby allowing for more detailed counseling, and instituting optimum therapy. This review highlights developments in prostate cancer imaging that may improve staging and treatment planning for prostate cancer patients.

[Diagnostic imaging of urolithiais. Current recommendations and new developments]. / Bildgebende Diagnostik bei Harnsteinen. Aktueller Stand und neue Trends.

BACKGROUND AND METHOD: Prevalence of urolithiasis is increasing in industrialized countries--in both adults and children, representing a unique diagnostic and therapeutic challenge. Risk-adapted diagnostic imaging currently means assessment with maximized sensitivity and specificity together with minimal radiation exposure. In clinical routine, imaging is performed by sonography, unenhanced computed tomography (NCCT) or intravenous urography (IVU) as well as plain kidney-ureter-bladder (KUB) radiographs. AIM: The aim of the present review is a critical guideline-based and therapy-aligned presentation of diagnostic imaging procedures for optimized treatment of urolithiasis considering the specifics in children and pregnant women.

Miniperc and retrograde intrarenal surgery: when and how?

CONTEXT: Extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCNL) are consolidated procedures for the treatment of kidney stones; however, their primary weak points are the lower efficacy of ESWL, especially for lower calyx stones, and the morbidity of PCNL resulting from the creation and dilation of the percutaneous trajectory. The increasing miniaturization of percutaneous surgery instrumentation and the development of retrograde intrarenal surgery (RIRS) are recent innovations. ACQUISITION OF EVIDENCE: A structured nonsystematic review was conducted through a literature search of articles published between 1997 and 2013, using the terms kidney stones, miniperc, mini-PCNL, RIRS and flexible ureteroscopy in the PubMed, Google Scholar and Scopus databases. SUMMARY OF THE EVIDENCE: RIRS requires greater surgical time, several procedures for voluminous stones and higher hospital costs, due in part to the relative fragility of the instruments. On the other hand, miniperc requires a longer hospital stay, an increased need for postoperative analgesia and a greater reduction in hemoglobin levels, although these do not translate into an increased rate of transfusions. CONCLUSIONS: The current treatment of kidney stones uses minimally invasive procedures such as miniperc and RIRS. The 2 procedures are equivalent in terms of efficacy (stone clearance) and are associated with minimal complications. Comparative prospective studies are necessary to determine the position of each of these techniques in the treatment of kidney stones. In our experience, the 2 techniques are complementary and should be part of the current urological therapeutic arsenal.

Live cell imaging by multifocal multiphoton microscopy.

Multifocal multiphoton microscopy (MMM) permits parallel multiphoton excitation by scanning an array of high numerical aperture foci across a plane in the sample. MMM is particularly suitable for live cell investigations since it combines advantages of standard multiphoton microscopy such as optical sectioning and suppression of out-of-focus phototoxicity with high recording speeds. Here we describe several applications of MMM to live cell imaging using the neuroendocrine cell line PC12 and bovine chromaffin cells. Stainings were performed with the acidophilic dye acridine orange and the lipophilic dyes FM1-43 and Fast DiA as well as by transfection of the cells with GFP. In both bovine chromaffin and PC12 cells structural elements of nuclear chromatin and the 3-D distribution of acidic organelles inside the cells were visualized. In PC12 cells differentiated by nerve growth factor examples of neurites were monitored. Stainings of membranes were used to reconstruct the morphology of cells and neurites in three dimensions by volume-rendering and by isosurface plots. 3-D reconstructions were composed from stacks of about 50 images each with a diameter of 30-100 microm that were acquired within a few seconds. We conclude that MMM proves to be a technically simple and very effective method for fast 3-D live cell imaging at high resolution.

Isolation of autophagocytosis mutants of Saccharomyces cerevisiae.

Protein degradation in the vacuole (lysosome) is an important event in cellular regulation. In yeast, as in mammalian cells, a major route of protein uptake for degradation into the vacuole (lysosome) has been found to be autophagocytosis. The discovery of this process in yeast enables the elucidation of its mechanisms via genetic and molecular biological investigations. Here we report the isolation of yeast mutants defective in autophagocytosis (aut mutants), using a rapid colony screening procedure.