The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice. 相似文献
The European Journal of Health Economics - The aims of this study were to assess whether there is a conceptual overlap between the questionnaires HIT-6 and EQ-5D and to develop a mapping algorithm... 相似文献
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Gefahrstoffe sind in der Arbeitswelt allgegenwärtig. Beschäftigte aus allen Branchen sind bei ihrer Arbeit mit... 相似文献
Patients with primary hyperparathyroidism are at risk for skeletal and renal end-organ damage.
Methods
We studied patients with biochemically confirmed primary hyperparathyroidism from 1995–2014 and quantified the frequency of osteoporosis, nephrolithiasis, hypercalciuria, and decrease in renal function.
Results
The cohort comprised 9,485 patients. In total, 3,303 (35%) had preexisting end-organ effects (osteoporosis, 24%; nephrolithiasis, 10%; hypercalciuria, 5%). Of 6,182 remaining patients, 1,769 (29%) exhibited progression to 1 or more end-organ effects over a median 3.7 years. Among patients with classic primary hyperparathyroidism (calcium and parathyroid hormone increased), progression was unrelated to the degree of hypercalcemia (calcium >11.5 mg/dL, hazard ratio 1.03, 95% confidence interval 0.85–1.25; 11.1–11.5 mg/dL, HR 1.07, 95% confidence interval 0.93–1.23; 10.5–11.0 mg/dL?=?reference). Patients with nonclassic primary hyperparathyroidism (calcium increased, parathyroid hormone 40–65 pg/mL) had a lesser risk of progression (calcium >11.5 mg/dL, hazard ratio 0.68, 95% confidence interval 0.50–0.94; 11.1–11.5 mg/dL, hazard ratio 0.68, 95% confidence interval 0.56–0.82; 10.5–11.0 mg/dL, hazard ratio 0.66, 95% confidence interval 0.59–0.74). End-organ damage developed before or within 5 years of diagnosis for 62% of patients.
Conclusion
End-organ manifestations of primary hyperparathyroidism develop before biochemical diagnosis or within 5 years in most patients. End-organ damage occurred more frequently in patients with classic primary hyperparathyroidism versus nonclassic primary hyperparathyroidism, regardless of severity of hypercalcemia. 相似文献
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system. 相似文献
The impact of obesity on patient-reported outcome (PRO) after total knee arthroplasty (TKA) surgery has demonstrated varying results. We evaluated knee pain, Activity in Daily Life function (ADL), and satisfaction after TKA surgery in patients with and without prior bariatric surgery (BS).
Methods
Scandinavian Obesity Surgery Registry (SOReg) and the Swedish Knee Arthroplasty Register (SKAR) were used to identify patients operated on with primary TKA for osteoarthritis (OA) between 2009 and 2019 that had a BS within 2 years before the TKA (BS group). These patients were compared to patients with TKA without prior BS (no BS group). The patients filled in the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively and one year postoperatively as well as satisfaction with the surgery one year postoperatively. Multiple linear regression analysis was used to evaluate 1-year postoperative KOOS pain and ADL function between the 2 groups. Adjustments were made for sex, age, and preoperative KOOS pain and ADL function respectively.
Results
Forty-four patients were included in the BS group and 3,525 patients in the no BS group. We found no statistically or clinically significant difference in one-year postoperative KOOS pain and ADL function between the BS group and the no BS group. The majority of the patients in both groups were classified as satisfied or very satisfied one year postoperatively to the TKA.
Conclusions
Our results indicate that patients without BS prior to the TKA gain similar 1-year outcome in pain, ADL function and satisfaction as patients with prior BS.
