Klinikum Weiden

Molecular diagnostics play a pivotal role in guiding therapy for metastatic colorectal cancer (mCRC). Current guidelines recommend stratification based on biomarkers such as RAS, BRAF, and DNA mismatch-repair (MMR) status to select between anti-EGFR (epidermal growth factor receptor) and anti-VEGF (vascular endothelial growth factor) therapies. This retrospective analysis evaluated the randomized FIRE-3 study that compared first-line treatment with FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab in RAS wild-type patients. The present analysis included 199 patients with RAS/BRAF wild-type MMR proficient tumors. Next-generation sequencing (NGS) was successfully performed in all patients and allowed stratification into hyperselected (no predefined genetic alterations) or gene altered subgroups using the previously published approach of the PRESSING-studies. Hyperselection according to PRESSING-3 was associated with a survival benefit from anti-EGFR-based therapy compared to bevacizumab (38.5 months vs. 27.5 months; HR 0.68; 95 % CI, 0.44-1.05; P = 0.08). This benefit was observed in both, right- and left-sided tumors, (HR 0.58 and HR 0.70). Patients with gene alterations showed inferior survival compared to hyperselected patients across all subgroups. In this unfavorable subgroup, application of cetuximab and bevacizumab were associated with comparable OS (total cohort: HR 1.04; 95 % CI, 0.61-1.79). Again, this finding was independent of primary tumor sidedness (left-sided tumors: HR 1.10; 95 % CI, 0.59-2.07; right-sided tumors: HR 1.05; 95 % CI, 0.31-3.55). Molecular hyperselection facilitated by next generation sequencing could replace primary tumor sidedness as a tool of decision making for optimal choice of targeted therapy in first-line treatment of RAS wild-type mCRC.

Background Several case series have highlighted the ADVOS hemodialysis system's efficacy in eliminating water-soluble and protein-bound substances across diverse patient populations, such as multiorgan failure, acute-on-chronic liver failure (ACLF), acidosis, and even COVID-19. The EMOS-Registry, a non-interventional, multi-center patient registry, amassed real-world evidence, culminating in the largest patient cohort treated with ADVOS to date. This study aims to present and analyze the final performance and safety outcomes from the entire dataset comprising 282 participants. Methods Data spanning from January 18, 2017, to August 31, 2020, were collected from five German hospitals, encompassing subsets of patients with acidosis and ACLF grade 3. Performance and safety were assessed through vital signs, clinical laboratory parameters and blood gas analyses. The SOFA Score-Standardized Mortality Ratio (SMR) served to evaluate patient outcomes in the absence of a control group. Results Participants, with a median age of 58 years, predominantly male (64%), exhibited a high requirement for mechanical ventilation (68%) and vasopressors (82%) with a median SOFA Score of 15. Notably, a median of 3 (IQR 2, 5) ADVOS sessions per patient were administered. Following the initial treatment, significant reductions were observed in bilirubin (-1.9 [CI 95% -1.3, -2.5]), creatinine (-0.5 [-0.4, -0.6]), and blood urea nitrogen (-13.1 mg/dL [-10.3, -16.0]) levels. Moreover, there were marked improvements in blood pH (7.34 vs. 7.41, p<0.001), HCO3- (19.4 vs. 24.6 mmol/l, p<0.001) and base excess (-5.6 vs. 0.2 mmol/l, p<0.001). The observed mortality rate (66%) was notably lower than the expected rate based on SOFA Score (84%), resulting in a SMR of 0.79 (95% CI: 0.66-0.93), with a calculated number needed to treat (NNT) of 5.8. Conclusions This study emphasizes the ADVOS system's efficacy in eliminating water-soluble and protein-bound substances and correcting acid-base imbalances across a diverse cohort with multiorgan failure. However, further validation through randomized controlled trials is warranted to solidify these findings.

Uncemented acetabular components are widely used in modern total hip arthroplasty (THA). Modularity has numerous advantages including the ability to use supplementary screw fixation for the shell, and allow to switch from ceramic to polyethylene (PE) bearings and vice versa, and the use of lipped and face-changing liners. Despite these advantages, a problem with modular PE liners is dissociation. This is a rare complication in modern implants. The rate of liner dissociation is reported to be very low between 0.17% and 0.8%. Typical symptoms are sudden onset of groin pain in a previously well-functioning hip joint, followed by grinding or clicking sensations during hip joint motions indicating, that the femoral head is articulating with the metal acetabular shell rather than with the PE liner. Any newly observed noise or squeaking from a THA should undergo radiographic investigation to exclude liner dissociation. We present the case of an 88-yearold male patient who developed PE liner dissociation in a cementless THA with a Pinnacle acetabular component six years after the index operation. We recommended revision of the left hip, which was performed two days later. In the interim, the patient was advised to use a pair of crutches. During revision surgery, it was observed that the metal head made contact with the cementless cup shell without damaging it from a macroscopic standpoint. Consequently, a simple exchange of the PE liner was conducted, and a 36 mm metal head was implanted due to scratches on the original head. Early diagnosis facilitates a straightforward exchange of the liner along with the head, potentially preserving the osseous integrated cup shell and stem integrity. Routine radiologic follow-up allows to distinguish between PE liner dissociation and severe PE wear.

Background: Trochanteric and subtrochanteric fractures result in nonunion in more than 20% of cases. The aim of this study was to assess the functional and radiological results following revision cephalomedullary nailing and 95-degree angled blade plating in aseptic trochanteric and subtrochanteric nonunion. Methods: In a retrospective multi-center study between January 2010 and December 2020, a total of 68 consecutive patients (21 women and 47 men) from two European level I trauma centers with the diagnosis of aseptic nonunion were recruited. Follow-up assessment and the patients' convenience were assessed using the Harris Hip Score, Visual Analog Scale for pain at rest and on stress/exertion and Short Form-12. Results: The patients' mean age was 57 (range 26-85) years. After a follow-up period of 12 months, one case of persistent nonunion in the cephalomedullary nail group and 10 cases in the blade plate group were identified. The mean duration of surgery was 137 ± 47 min in the cephalomedullary nail group and 202 ± 59 min in the blade plate group (<0.0001). Short-term postoperative complications included wound dehiscence, bleeding, mismatched screw and hematoma. The mid-term results 12 months after surgical revision demonstrated significantly different osseous union rates (p = 0.018). The long-term functional outcome according to the Harris Hip Score 6 years (range 2-10) after revision surgery demonstrated 81 ± 21 points in the cephalomedullary nail group and 64 ± 23 points in the plate group (p = 0.026). Conclusions: This study demonstrated that the revision treatment of trochanteric and subtrochanteric nonunion using a 95-degree blade plate or cephalomedullary nail resulted in a high percentage of osseous union, with a low incidence of complications and good functional results for both methods.

3550 Background: Doublet chemotherapy plus bevacizumab is a well-established standard of care in the first-line treatment of RAS-mutant (RASmut) metastatic colorectal cancer (mCRC). The FIRE-3 trial was the first randomized study to compare FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab in mCRC. Since this trial initially included patients irrespective of RAS mutation status, the present analysis performs an updated evaluation of therapeutic efficacy of targeted therapy with bevacizumab versus cetuximab in RASmut mCRC. Methods: FIRE-3 trial included 752 patients. Initially, pyrosequencing (PSeq) was used to identify RAS mutations. In a subsequent investigation next-generation sequencing (NGS) was applied in 373 available tumors. A 5% mutant allele cutoff was used for both PSeq and NGS both of which were done centrally. Results: Of the 224 RASmut and BRAF wild-type patients, 187 were identified by polymerase chain reaction (PCR) and PSeq, 122 by NGS. 86 tumors were PCR positive and NGS positive (PCR+/NGS+), 36 tumors PCR negative and NGS positive (PCR-/NGS+). In the overall RASmut cohort of 224 patients, no overall survival (OS) benefit was observed when cetuximab was compared to bevacizumab (20.3 months vs 21.1 months; HR 1.028; 95% CI, 0.547-1.583; P=.842). This effect was observed independent of sidedness of primary tumors (PT) for left-sided (21.5 months vs 22.1 months; HR 1.054; 95% CI, 0.763-1.456) and right-sided PT (19.2 months vs 19.5 months; HR 0.931; 95% CI, 0.547-1.583). Conclusions: While cetuximab notably is not effective in RASmut mCRC, this randomized comparison does not provide an indication for superior efficacy of bevacizumab in the first-line treatment of this patient group. Trial identification number: NCT00433927 [clinicaltrials.gov]

BackgroundHeart failure–related cardiogenic shock (HF-CS) accounts for a significant proportion of all CS cases. Nevertheless, there is a lack of evidence on sex-related differences in HF-CS, especially regarding use of treatment and mortality risk in women vs. men. This study aimed to investigate potential differences in clinical presentation, use of treatments, and mortality between women and men with HF-CS.MethodsIn this international observational study, patients with HF-CS (without acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled between 2010 and 2021. Logistic and Cox regression models were used to assess differences in clinical presentation, use of treatments, and 30-day mortality in women vs. men with HF-CS.ResultsN = 1030 patients with HF-CS were analyzed, of whom 290 (28.2%) were women. Compared to men, women were more likely to be older, less likely to have a known history of heart failure or cardiovascular risk factors, and lower rates of highly depressed left ventricular ejection fraction and renal dysfunction. Nevertheless, CS severity as well as use of treatments were comparable, and female sex was not independently associated with 30-day mortality (53.0% vs. 50.8%; adjusted HR 0.94, 95% CI 0.75–1.19).ConclusionsIn this large HF-CS registry, sex disparities in risk factors and clinical presentation were observed. Despite these differences, the use of treatments was comparable, and both sexes exhibited similarly high mortality rates. Further research is necessary to evaluate if sex-tailored treatment, accounting for the differences in cardiovascular risk factors and clinical presentation, might improve outcomes in HF-CS.Graphical abstractSex-related differences in clinical characteristics, shock severity, and mortality in patients with heart failure–related cardiogenic shock. Summary for the main study findings. AMI, acute myocardial infarction; CI, confidence interval; HF-CS, heart failure–related cardiogenic shock; LVEF, left ventricular ejection fraction; MCS, mechanical circulatory support; SCAI, Society for Cardiovascular Angiography & Interventions.