Kliniken

Shortcoming of the Mouse Model of Postoperative Ileus

2025-11-30T00:00:00Z

Shortcoming of the Mouse Model of Postoperative Ileus von Stumberg, Maximiliane; Akinci, Ejder; Ertim, Berkan; Oetzmann von Sochaczewski, Christina Background/Objectives: The mouse model of postoperative ileus separates the gastrointestinal tract into 15 sections, 10 of which are in the small intestine, to measure intestinal transit time. Usually, mice are standardised according to age or body weight. This inherently assumes that intestinal lengths are similar among the included mice irrespective of the method of standardisation. We aimed to test this assumption by comparing intestinal lengths, measuring their variability in commonly used out- and inbred strains. Methods: Mice were humanely killed, and their intestines were removed and measured in a standardised fashion. We compared the coefficients of variability via the modified signed-rank likelihood test. Results: We included 125 mice of the Crl:CD1(ICR) background and 10 mice of the C57Bl/6J and C57Bl/6NCrl substrains. The mean small intestinal length of Crl:CD1(ICR) mice was 437 mm (standard deviation 54), while it was 473 mm (standard deviation 29) in C57Bl/6J mice and 419 mm (standard deviation 57) in C57Bl/6NCrl mice. The respective coefficients of variation were 12.4%, 6.1%, and 13.6% and did not differ between the out- and inbred strains (modified signed likelihood ratio 5.878, p = 0.053). This was not the case for caecal and large intestinal lengths. Conclusions: Due to substantial variation in small intestinal length, the separation of the small intestine into ten equally sized segments to measure intestinal transit time might not be warranted. This could be addressed by measuring small intestinal transit time in absolute values and relative to the intestinal length.

Post-Surgical Outcomes of Kidney-Sparing Surgery vs. Radical Nephroureterectomy for Upper-Tract Urothelial Cancer in a Propensity-Weighted Cohort

2025-08-25T00:00:00Z

Post-Surgical Outcomes of Kidney-Sparing Surgery vs. Radical Nephroureterectomy for Upper-Tract Urothelial Cancer in a Propensity-Weighted Cohort Büttner, Thomas; Pooyeh, Armin; Ritter, Manuel; Hauser, Stefan Objectives: In localized upper-tract urothelial carcinoma (UTUC), radical nephroureterectomy (RNU) represents the surgical gold standard, but kidney-sparing surgery (KSS) offers an alternative. The surgical perspective, including complications, remains understudied in this context. This study aimed to compare KSS and RNU, assess kidney function and survival, and identify the surgical risk factors. Methods: This retrospective analysis included UTUC patients undergoing KSS (n = 46) or RNU (n = 46) at a single center from 2016 to April 2024, matched by propensity scores. The primary endpoint was Clavien–Dindo complications. Other endpoints included Days Alive and Out of the Hospital within 30 days (DAOH30), changes in the eGFR, cancer-specific survival (CSS), and disease-free survival (DFS). A UTUC Surgery Risk Score was developed to identify the surgical risk factors for severe complications. Results: KSS was significantly associated with higher rates of Clavien–Dindo grades ≥ 3 (KSS: 14; RNU: 3). DAOH30 was significantly longer following RNU. The UTUC Surgery Risk Score, based on a non-endoscopic KSS approach, an ASA score ≥ 3, and preoperative creatinine > 0.9 mg/dL, was significantly associated with overall and severe complications and DAOH30 (both p < 0.001). KSS showed significantly better early postoperative eGFR preservation (+0.55 mL/min vs. -4.3 mL/min for RNU, p = 0.015). No significant differences were observed in the median CSS or DFS between the groups. Conclusions: KSS is associated with a higher rate of certain postoperative complications,but offers superior kidney function preservation, with comparable oncological outcomes to RNU. The novel UTUC Surgery Risk Score can aid in patient counseling and personalized decision-making prior to surgery.

Evaluating Sorafenib (SORA-2) as Second-Line Treatment for Unresectable Hepatocellular Carcinoma

2025-03-13T00:00:00Z

Evaluating Sorafenib (SORA-2) as Second-Line Treatment for Unresectable Hepatocellular Carcinoma Möhring, Christian; Berger, Moritz; Sadeghlar, Farsaneh; Zhou, Xin; Zhou, Taotao; Monin, Malte Benedikt; Shmanko, Kateryna; Welland, Sabrina; Sinner, Friedrich; Schwacha-Eipper, Birgit; Bauer, Ulrike; Roderburg, Christoph; Pirozzi, Angelo; Ben Khaled, Najib; Schrammen, Peter; Balcar, Lorenz; Pinter, Matthias; Ettrich, Thomas J.; Saborowski, Anna; Berres, Marie-Luise; De Toni, Enrico N.; Lüdde, Tom; Rimassa, Lorenza; Ehmer, Ursula; Venerito, Marino; Radu, Iuliana-Pompilia; Schmidt-Wolf, Ingo G. H.; Weinmann, Arndt; Vogel, Arndt; Schmid, Matthias; Kalff, Jörg C.; Strassburg, Christian P.; Gonzalez-Carmona, Maria A. Background/Objectives: Systemic treatment for unresectable hepatocellular carcinoma (HCC) has rapidly advanced, with immune checkpoint inhibitors now the preferred first-line option. However, with multiple agents available and no established treatment sequence, selecting the most suitable second-line (2L) therapy remains challenging. While sorafenib is frequently chosen for 2L treatment, comprehensive data supporting its use is limited. This study evaluates the effectiveness of sorafenib as 2L therapy and factors influencing outcomes following first-line treatment failure in advanced HCC patients. Methods: This is a retrospective, multicenter study, including 81 patients with unresectable HCC from 12 European centers who received sorafenib as 2L treatment. Median overall survival (mOS), median progression-free survival (mPFS), radiological response to treatment, and toxicity were evaluated. Univariable and multivariable analyses were performed to identify potential predictors of clinical benefit. Results: In this cohort, some patients were treated with 2L sorafenib mOS for 7.4 months (95% CI: 6.6–13.6) and other patients were treated with mPFS for 3.7 months (95% CI: 3.0–4.8). Multivariable analysis revealed the best median OS for patients with CP A and AFP levels < 400 ng/mL (15.5 months). Adverse events (AE) of grade ≥ 3 were reported in 59.4% of patients. Conclusions: In this real-world cohort of European patients with unresectable HCC, the outcome of sorafenib treatment in the 2L setting was comparable to that of the other established 2L treatment options in patients with preserved liver function and good performance status. This study contributes to the understanding of the role of sorafenib in the 2L setting and underscores the need for further research to identify predictive factors for response and survival in order to optimize treatment algorithms for advanced HCC.

In Vivo Cone Photoreceptor Topography of the Human Foveola

2025-08-06T00:00:00Z

In Vivo Cone Photoreceptor Topography of the Human Foveola Ameln, Julius; Witten, Jenny L.; Gutnikov, Aleksandr; Lukyanova, Veronika; Holz, Frank G.; Harmening, Wolf M. PURPOSE. To study in vivo cone topography of the normal human foveola.
METHODS. The fovea in both eyes of 30 healthy participants was imaged with adaptive optics scanning light ophthalmoscopy. High-resolution image montages spanning two degrees of visual angle were created and cone center locations annotated. Continuous cone density maps were computed by a Voronoi cell area approach to also yield the topographical center, the cone density centroid (CDC). Cone density profiles were extracted and fit with a four-parameter decay function, D = D₀ / (1 + (E/a)^b)^c, with D as cone density (cones/mm²), D₀ as cone density at the CDC, and E as eccentricity (µm).
RESULTS. Across eyes, D₀ was 175,474 ± 20,543 cones/mm², on average (range 136,001–216,209 cones/mm²). Density dropped anisotropically along the meridians, shallower horizontally, with average best fit parameters (a, b, c) of 61.95, 2.469, 0.268 for horizontal, and 59.11, 2.012, 0.357, for vertical profiles, respectively. In radially averaged profiles, cone density reached 50% of D₀ at 151 ± 17 µm eccentricity (range 128–193 µm). Temporal cone density was slightly higher than nasal. Most topographical metrics were highly correlated between fellow eyes.
CONCLUSIONS. Despite a 1.6-fold range in absolute cone density, foveolar density profiles could be well described by a sigmoidal decay function across all eyes. This established a normative cone density profile of the healthy foveola. It allowed cone density estimation in cases of only partially available data, which alleviates resolution demands for future studies and renders possible retrospective analyses of foveolar cone topography in suboptimal imagery.