Lundsgaardholst1874

KRAS mutations are the most frequent gain-of-function alterations in patients with lung adenocarcinoma (LADC) in the Western world. Although they have been identified decades ago, prior efforts to target KRAS signaling with single-agent therapeutic approaches such as farnesyl transferase inhibitors, prenylation inhibition, impairment of KRAS downstream signaling, and synthetic lethality screens have been unsuccessful. Moreover, the role of KRAS oncogene in LADC is still not fully understood, and its prognostic and predictive impact with regards to the standard of care therapy remains controversial. Of note, KRAS-related studies that included general non-small cell lung cancer (NSCLC) population instead of LADC patients should be very carefully evaluated. Recently, however, comprehensive genomic profiling and wide-spectrum analysis of other co-occurring genetic alterations have identified unique therapeutic vulnerabilities. Novel targeted agents such as the covalent KRAS G12C inhibitors or the recently proposed combinatory approaches are some examples which may allow a tailored treatment for LADC patients harboring KRAS mutations. This review summarizes the current knowledge about the therapeutic approaches of KRAS-mutated LADC and provides an update on the most recent advances in KRAS-targeted anti-cancer strategies, with a focus on potential clinical implications.Purpose Treatment with dopamine agonists (DA) is highly effective in patients with prolactinomas. In selected patients, discontinuation of DA after several years of successful treatment is possible, however, hyperprolactinemia recurs in 60-80% of them. It is unclear what is the clinical significance of these recurrences and hence, whether or not reinitiation of therapy is necessary. Objectives To evaluate the recurrence rate in prolactinoma patients after DA withdrawal and the necessity to restart treatment. Methods Patients with >2 years of treatment with cabergoline (CBG) who achieved normoprolactinemia and a > 50% reduction in tumor size were included. DA dose was down titrated until withdrawal. Basal tumor size, as well as PRL and gonadal steroid levels were recorded at diagnosis, at withdrawal of DA and every 3-6 months for 1-3 years. Results Fifty patients were included (38 women, 34 macroprolactinomas). After withdrawal, 34 (68%) presented recurrence of hyperprolactinemia. PRL levels less then 5 ng/mL at the time of withdrawal predicted remission (sensitivity 76%, specificity of 63%). CBG was restarted in eight patients (23%) because of the presence of hypogonadism. CBG was withheld in the remaining 26, based on the following arguments (1) premenopausal women without biochemical hypogonadism, (54%); (2) asymptomatic men under 65 without biochemical hypogonadism (19%); (3) asymptomatic postmenopausal women (19%); (4) asymptomatic men over 65 (8%). After a median follow-up of 30 months, no increase in PRL levels or tumor growth was documented. Conclusions Biochemical recurrence in prolactinomas is very frequent, however, in only a few of these patients reinitiation of DA is necessary.Objectives To assess if (I) the alveolar bone defect configuration at dental implants diagnosed with peri-implantitis is related to clinical parameters at the time of surgical intervention and if (II) the outcome of surgical intervention of peri-implantitis is dependent on defect configuration at the time of treatment. Materials and methods In a prospective study, 45 individuals and 74 dental implants with ≥ 2 bone wall defects were treated with either an autogenous bone transplant or an exogenous bone augmentation material. Defect fill was assessed at 1 year. Results At baseline, no significant study group differences were identified. Most study implants (70.7%, n = 53) had been placed in the maxilla. Few implants were placed in molar regions. The mesial and distal crestal width at surgery was greater at 4-wall defects than at 2-wall defects (p = 0.001). Probing depths were also greater at 4-wall defects than at 2-wall defects (p = 0.01). Defect fill was correlated to initial defect depth (p less then 0.001). Defect fill at 4-wall defects was significant (p less then 0.05). Conclusions (I) The buccal-lingual width of the alveolar bone crest was explanatory to defect configuration, (II) 4-wall defects demonstrated more defect fill, and (III) deeper defects resulted in more defect fill.Objective Technical description of minimally invasive double-plating of the distal femur. Indications Peri- and interprosthetic distal femur fractures with limited (periprosthetic) bone stock in geriatric patients. Re-operations (delayed and non-unions; infected non-unions) of the distal femur. Distal femoral fractures or femoral shaft fractures that do not qualify for femoral nailing and where the patient is unable to comply with weight-bearing restrictions. Contraindications Peri- and interprosthetic femoral fractures with unstable knee prosthesis and local soft tissue infection. Peri- and interprosthetic fractures of the proximal femur. Surgical technique Supine position on a radiolucent table with both legs draped free. Support the knee to release traction on the distal fragment by the gastrocnemius muscle. Reduction and fixation of the fracture using a minimally invasive lateral approach. Usp22i-S02 inhibitor To reduce stress riser zones in interprosthetic fractures, the fixation device should overlap both the prosthesis by cture. No implant failure or loss of reduction was seen after postoperative unrestricted weight bearing. In the additional 5 cases double-plating was used in salvage procedures ([infected] non-unions, hardware failure). One of these patients developed a fracture-related infection for which all material was removed. The fracture healed after a new attempt of antegrade nailing combined with an additional locking plate. In the remaining patients complete bone healing without hardware failure was seen.Numerous imaging modalities may be used for the staging of women with advanced breast cancer. Although bone scintigraphy and multiplanar-CT are the most frequently used tests, others including PET, MRI and hybrid scans are also utilised, with no specific recommendations of which test should be preferentially used. We review the evidence behind the imaging modalities that characterise metastases in breast cancer and to update the evidence on comparative imaging accuracy.