Background/Objectives: The transradial approach is widely used for vascular access in many disciplines. Radial artery occlusion (RAO) is a frequent sequel, and hand/arm pain affects 7.8% of patients. We aimed to elucidate whether RAO or ulnar artery occlusion (UAO) causes impaired neural blood flow and, thus, if symptoms may be attributable to claudication or nerve damage. Methods: Forty healthy volunteers (73% female), with a mean age of 38 years and without clinical or sonographic signs of carpal tunnel syndrome, were included. All underwent a standardized ultrasound examination (Aplio i800 and i22LH8 linear transducer, Canon Medical Systems) of the forearm, investigating the median nerve and its intraneural blood flow as well as the vascular status of the limb. The radial and ulnar arteries were then sequentially compressed, while changes to intraneural blood flow were noted. Thereafter, the (reverse) Barbeau test and the (inverse) modified Allen Test (MAT) were performed. Results: Simulated RAO and UAO halted intraneural blood flow in 65% and 62.5% of individuals, respectively. A total of 32.5% of participants reported discomfort in the hand/arm. Absent flow during occlusion was found at a significantly higher rate in symptomatic individuals. MAT and inverse MAT were abnormal (>10 s) in 17.5% and 7.5% of patients. Barbeau and reverse Barbeau produced type D results in 15% and 20%, respectively. Conclusions: Both simulated RAO and UAO caused the cessation of intraneural blood flow of the median nerve in two-thirds of participants, and a large proportion reported symptoms. MAT and Barbeau tests did not seem to be useful in predicting impaired neural blood flow.
BACKGROUND/AIMS:Posterior capsule opacification (PCO) is the most frequent long-term complication after cataract surgery, caused by proliferation of residual lens epithelial cells (LECs). Metformin, a common antidiabetic drug with antifibrotic properties, may act as a pharmacological modulator of this process. The purpose was to assess whether systemically administered metformin reaches the human lens capsule and inhibits LEC proliferation at physiologically relevant concentrations. METHODS:Metformin concentrations were quantified in serum and lens capsule tissue of patients with type 2 diabetes mellitus undergoing cataract surgery using high performance liquid chromatography-tandem mass spectrometry. Patients were stratified into low-dose (≤1000 mg/day) and high-dose (>1000 mg/day) groups. Additionally, anterior lens capsules from non-diabetic donors were cultured with or without metformin (0.75 pg/µL), and LEC proliferation was monitored for 14 days by live-cell imaging. RESULTS:Metformin was detectable in both serum and capsule specimens, with a significant correlation between compartments (r=0.553, p=0.011). Capsule concentrations were similar across dose groups, while serum levels were higher in the low-dose group. In vitro, metformin significantly reduced LEC proliferation compared with controls (p<0.001). CONCLUSION:Systemically administered metformin reaches the human lens capsule in vivo and suppresses LEC proliferation in vitro at clinically relevant concentrations. These findings provide first clinical and experimental evidence supporting metformin as a potential pharmacological adjunct to current strategies for PCO prevention.
Die Leitlinie nimmt Bezug auf die Diagnostik einschließlich begleitender Autoimmunerkrankungen bei Typ-1-Diabetes mellitus, die Insulintherapie und die glykämischen Zielwerte.
The biological effects of progesterone are mediated through the RANK/RANK-ligand system, which promotes tumor growth and malignant behavior in breast cancer models. In the large prospective, double-blind, placebo-controlled, phase 3 ABCSG 18 trial we have demonstrated that the addition of the RANK ligand denosumab dramatically reduces fractures compared to placebo, but also improves disease-free survival (DFS), and overall survival (OS) in aromatase inhibitor-treated postmenopausal patients with early luminal breast cancer. Tumor histological grade, as well as immunohistochemically quantified Ki-67, estrogen receptor (ER), and progesterone receptor (PR) data were collected from 2,026 patients. ER and PR were assessed according to the Allred score and considered positive if ≥3. Disease-free survival (DFS), distant recurrence-free (DRFS), and overall survival (OS) data were prospectively collected during a median follow-up (FU) of 8.1 years as part of the ABCSG 18 study. Cox Models were used to evaluate the association with outcome. Overall, luminal A-like tumors had a better DFS, DRFS, and OS than luminal B-like tumors, but PR expression per se was not prognostic in this large prospective clinical trial. Patients with PR positive tumors, however, who were treated with denosumab, enjoyed a considerably better long-term outcome than patients who had been randomized to the placebo arm (HR for DFS: 0.80; 95% CI 0.65-0.98; HR for DRFS: 0.68; 95% CI 0.51-0.90; HR for OS 0.63; 95% CI 0.46-0.88). In contrast, in patients with PR-negative tumors, no differences in long-term outcomes between the denosumab or placebo arm of the trial were observed (HR for DFS: 0.87; 95% CI 0.46-1.64; HR for DRFS: 1.19; 95% CI 0.53-2.66; HR for OS 0.99; 95% CI 0.37-2.65). While the HR for DFS in denosumab vs placebo patients remained stable with increasing Allred scores, HRs for DRFS and OS improved with increasing Allred scores, thereby suggesting that the efficacy of denosumab depends on the degree of intra-tumoral PR expression. Our results indicate that the long-term outcome benefit for adjuvant denosumab in this large prospective randomized placebo-controlled trial is driven by patients with PR-positive tumors. The disruption of PR signaling, either via PR antagonization or by RANKL inhibition, could therefore be a promising therapeutic strategy in luminal breast cancer. C. Singer, D. Hlauschek, D. Egle, A. Reiner, G. G. Steger, G. Huber, R. Greil, G. Rinnerthaler, F. Fitzal, C. Brunner, C. Suppan, G. Pfeiler, S. P. Gampenrieder, M. Seifert, S. Kacerovsky-Strobl, C. Deutschmann, K. Wimmer, M. Balic, R. Jakesz, C. Fesl, H. Fohler, M. Gnant. The improved long-term outcome in denosumab-treated postmenopausal women with early luminal breast cancer in Abcsg 18 is driven by progesterone receptor-positive tumors [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-07-11.
Background. In very elderly pts with NDMM data on the efficacy of Isatuximab-lenalidomide-dexamethasone (Isa-Rd) induction therapy followed by Isa-R maintenance therapy compared to Rd induction followed by R maintenance are not available so far. Aim. In this prospective, randomized study, we aimed to evaluate potential benefits of combining Isa with Rd induction and R maintenance therapy with special focus on results after end of induction therapy. Methods. Pts were randomized to either 8 cycles of Isa-Rd or Rd; Isa 10mg/kg on d 1, 8, 15, 22 in cycle 1, subsequently on d 1 and 15; R 25mg, d 1-21 q 28 d, dexamethasone 40mg once weekly (20mg in pts aged ≥75 years). Maintenance therapy was administered for 24 cycles; Isa was given at 10mg/kg q 28 d, and R at 5-10mg, d 1-21 q 28 d. MRD was evaluated at the end of induction therapy using NGF with a sensitivity of 10-6. Circulating tumor cells (CTC) were assessed at d 1 and 8 of the study. OS estimates were calculated according to Kaplan-Meier, and survival curves were compared using the log-rank test. This trial is registered on ClinicalTrials.gov (NCT04891809). Results. One hundred thirty-seven pts have been enrolled. Median age was 77 yrs (range 70-91 yrs), ISS stage I/II/III: 41 (29.9%)/47 (34.3%)/46 (33.6%), ECOG status 0/1/2: 36 (26.2%)/70 (51.1%)/31 (22.6%). Cytogenetics: t(4;14) 8 (5.8%), t(14;16) 4 (2.9%), del17p 21 (15.3%), ampl1q21 31 (22.6%) of 110-115 pts with results available. Median follow-up was 18.4 mos. The efficacy analysis was performed on the per protocol population, resulting in evaluable response data for 100 pts (50 in each study arm). The median time to best response was 7.3 mos; Isa-Rd (7.0 mos) and the Rd (7.3 mos). All but 8 pts achieved an initial response (≥PR). Response rates were as follows: CR: 26% vs. 10%, p=0.066, VGPR: 36% vs. 20%, p=0.118, PR: 32% vs. 60%, p=0.009, and ORR: 94% vs. 90%, p=0.715, respectively. MR was observed in 6 (6%), and SD in 2 (2%) pts. MRD testing was performed in 92 pts after the end of 8 induction cycles. MRDneg at 10-6 was achieved in 20/52 (34.6%) pts of the Isa-Rd and in 1/40 (2.5%) of the Rd group, resulting in a significant difference in favour of Isa-Rd (p<0.001). MRDneg rates were similar in pts with/without HR cytogenetics. PFS analysis shows a median PFS of 31.8 in the Isa-Rd vs. 22.2 mos in the Rd group, respectively (p=0.017) (Figure 1). A tendency for improved OS was observed in the Isa-Rd group (median OS not reached vs. 48.1 mos, p=0.088; 2-year OS rate 88.2% vs. 70.8%). CTC data were available in 64 pts. Those with CTC detectable at d 8 had significantly shorter PFS (p=0.031). The PFS rate at 24 mos was 28.3% in CTC pos. vs. 73.9% in CTC neg. pts, respectively. Grade ≥3 hematologic AEs, which occurred in ≥10% of pts, were neutropenia (28.5%/19.0%), anemia (24.8%/8.8%), thrombocytopenia (16.8%/5.8%). Grade ≥3 non-haematological AEs in ≥10% of pts, were infections (57.7%/19.7%), pain (43.8%/7.3%), edema (23.4%/0.7%), asthenia (22.6%/4.4%), diarrhea (19.7%/0%), constipation (15.3%/1.5%), rash (14.6%/2.2%), dyspnea (13.9%/1.5%) and polyneuropathy (10.9%/0%). Procedural complications (9 [12.9%] vs. 0, p=0.003), and weight loss (6 [8.6%] vs. 0, p=0.028) were more frequent in the Isa-Rd group. Conclusions. Our data show a significantly higher CR/VGPR and MRDneg rate and longer PFS and with Isa-Rd compared to Rd (35.4% vs. 2.5%) induction therapy in very elderly pts with NDMM. Updated results will be presented.
