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1.
Naveen Pemmaraju MD Jacqueline S. Garcia MD Andrew Perkins MBBS PhD Jason G. Harb PhD Andrew J. Souers PhD Michael E. Werner PhD Christopher M. Brown PhD Francesco Passamonti MD 《Cancer》2023,129(22):3535-3545
Myelofibrosis is a heterogeneous myeloproliferative neoplasm characterized by chronic inflammation, progressive bone marrow failure, and hepatosplenic extramedullary hematopoiesis. Treatments like Janus kinase inhibitor monotherapy (e.g., ruxolitinib) provide significant spleen and symptom relief but demonstrate limited ability to lead to a durable disease modification. There is an urgent unmet medical need for treatments with a novel mechanism of action that can modify the underlying pathophysiology and affect the disease course of myelofibrosis. This review highlights the role of B-cell lymphoma (BCL) protein BCL-extra large (BCL-XL) in disease pathogenesis and the potential role that navitoclax, a BCL-extra large/BCL-2 inhibitor, may have in myelofibrosis treatment. 相似文献
2.
Brian C. Werner 《Arthroscopy》2019,35(4):1072-1073
Achieving tendon-bone healing continues to be challenging after arthroscopic rotator cuff repair, particularly for larger tears, despite significant improvements in repair techniques and implants. Considerable effort has been invested in research to identify methods to improve healing, including patches and injectable biologics. Parathyroid hormone improves tendon-to-bone healing. Teriparatide is osteogenic, stimulating bone growth, and chondrogenic, promoting cartilage formation at the enthesis. However, it could be difficult to justify the expense and potential risk of systemic administration of a recombinant hormone to improve structural healing until improvement in clinical outcomes can be shown. 相似文献
3.
M.F. Werner A. López-Rueda F.X. Zarco J. Blasco L. San Román S. Amaro E. Carrero R. Valero L. Oleaga J.M. Macho N. Bargalló 《Radiologia》2019,61(2):143-152
Purpose
Endovascular treatment with mechanical thrombectomy devices demonstrated high recanalization rates but functional outcome did not correlate with high rates of recanalization obtained. Patient selection prior to the endovascular treatment is very important in the final outcome of the patient. The primary aim of our study was to evaluate the prognostic value of posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) and Pons-Midbrain Index (PMI) scores in patients with Basilar Artery Occlusion (BAO) treated with successful angiographic recanalization after mechanical thrombectomy.Methods
Retrospective single-center study including 18 patients between 2008 and 2013 who had acute basilar artery occlusion managed with endovascular treatment within 24 hours from symptoms onset and with successful angiographic recanalization. The patients were initially classified into two groups according to clinical outcome and mortality at 90 days. For analysis we also divided patients into groups based on pc-ASPECTS (≥8vs.< 8) and PMI (≥3vs.< 3) on non-contrast CT (NCCT) and CT Angiography Source Images (CTASI). Imaging data were correlated to clinical outcome and mortality rate.Results
CTASI pc-ASPECTS, dichotomized at < 8 versus≥8, was associated with a favorable outcome (RR: 2.6; 95% CI: 1.3-5.2) and a reduced risk of death (RR: 6.5: 95% CI: 7.8-23.3). All patients that survived and were functionally independent had pc-ASPECTS score≥8. None of the 5 patients with CTASI pc-ASPECTS score less than 8 survived.Conclusion
PC-ASPECTS on CTASI is helpful for predicting functional outcome after BAO recanalization with endovascular treatment. These results should be validated in a randomized controlled trial in order to decide whether or not to treat a patient with BAO. 相似文献4.
5.
6.
Noemie Luong-Gardiol Imran Siddiqui Irene Pizzitola Beena Jeevan-Raj Mélanie Charmoy Yun Huang Anja Irmisch Sara Curtet Georgi S. Angelov Maxime Danilo Mélanie Juilland Beat Bornhauser Margot Thome Oliver Hantschel Yves Chalandon Gianni Cazzaniga Jean-Pierre Bourquin Joerg Huelsken Werner Held 《Cancer cell》2019,35(4):649-663.e10
7.
Anthony W. Tolcher Razelle Kurzrock Vincente Valero Rene Gonzalez Rebecca S. Heist Antoinette R. Tan Julie Means-Powell Theresa L. Werner Carlos Becerra Chenxi Wang Cathrine Leonowens Shanker Kalyana-Sundaram Joseph F. Kleha Jennifer Gauvin Anthony M. DAmelio Catherine Ellis Nageatte Ibrahim Li Yan 《Cancer chemotherapy and pharmacology》2020,85(4):673-683
This study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition. This was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD. Adverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses). Continuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested. 相似文献
8.
Robert Kowalczyk Krzysztof Nowosielski Ida Cedrych Marek Krzystanek Iwona Glogowska Joanna Streb Jakub Kucharz Zbigniew Lew-Starowicz 《Clinical breast cancer》2019,19(1):e30-e39
Introduction
Knowing the important factors influencing sexual function and body image might facilitate the recovery process of breast cancer survivors. Surgery type, relationship quality, and partner support might be modified to create a space for psychosexual intervention.Patients and Methods
This retrospective questionnaire-based study was performed on 128 women aged 18 to 65 years who were free of disease at time of study entry and who underwent surgical treatment for breast cancer. Diagnostic and Statistical Manual of Mental Disorders criteria were used to assessed female sexual dysfunction (FSD). Changes in Sexual Functioning Questionnaire (CSFQ) were used to measure sexual function, whereas the Body Image After Breast Cancer Questionnaire (BIBCQ) was used to assess body image. The support of the partner was evaluated by the Provisions of Social Relation Scale (PSRS).Results
The median age of the studied respondents was 52.5 ± 10.1 years. FSD was diagnosed in 27.3% women. Lower physical satisfaction in relationship (odds ratio [OR] = 2.3), undergoing mastectomy (OR = 4.1) higher level of anxiety (OR = 4.2), and shorter duration of relationship (OR = 1.1) as well as not receiving adjuvant chemotherapy (F = 3.54), higher level of emotional satisfaction in relationship (F = 20.32), longer time after completion of oncologic treatment (F = 8.76), undergoing breast-conserving therapy (compared to mastectomy) (F = 13.21), and lower level of anxiety (F = 31,25) were important factors for the prevalence of FSD and positive body image, respectively.Conclusion
Type of surgery, time after completion of treatment, level of anxiety, adjuvant chemotherapy, partner support, and satisfying quality of relationship are important factors for sexual function, sexual quality of life, and body image in female breast cancer survivors. 相似文献9.
Volker Heinemann Ludwig Fischer von Weikersthal Thomas Decker Alexander Kiani Florian Kaiser Salah-Edin Al-Batran Tobias Heintges Christoph Lerchenmüller Christoph Kahl Gernot Seipelt Frank Kullmann Markus Moehler Werner Scheithauer Swantje Held Lisa Miller-Phillips Dominik Paul Modest Andreas Jung Thomas Kirchner Sebastian Stintzing 《British journal of cancer》2021,124(3):587
Background Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.Methods The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated.Results Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours.Conclusions FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases.ClinicalTrials.gov identifier .Subject terms: NCT00433927Oncology, Biomarkers 相似文献
10.
Brenda Laky Isabella Alram Julia K. Frank Leo Pauzenberger Werner Anderl Karl-Heinz Wagner Philipp R. Heuberer 《Journal of orthopaedic research》2020,38(9):2074-2082
Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case-control single-center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5-scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection-related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 μmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 μmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C-reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 μmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5-year infection survival-rate was 65.6% for patients with preoperative bilirubin levels < 8.72 μmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 μmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 μmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched-controls. 相似文献