Existing fixation modalities for Jones type fifth metatarsal fracture fixation pose high rates of complications and nonunion

Jones type fifth metatarsal fractures pose a challenge to the foot and ankle surgeon, given documented high nonunion rates as well as high complication rates including hardware prominence, nerve injury, and screw breakage for existing treatment modalities including screw and plantar plate fixation. We call for the design of innovative Jones-fracture specific implants which contour to the natural curve of the fifth metatarsal. Future research should aim to expand upon existing literature for Jones fracture fixation and evaluate efficacy of novel implants which are designed to address unacceptably high complication rates for existing treatment modalities.     

Trends in radiation dose for low grade gliomas across the United States

Journal of Neuro-Oncology - Adjuvant radiation is often used in patients with low grade gliomas with high-risk characteristics with a recommended dose of 45–54 Gy. We used the...     

Peri-operative tobacco cessation interventions: a systematic review and meta-analysis

Tobacco smoking is associated with a substantially increased risk of postoperative complications. The peri-operative period offers a unique opportunity to support patients to stop tobacco smoking, avoid complications and improve long-term health. This systematic review provides an up-to-date summary of the evidence for tobacco cessation interventions in surgical patients. We conducted a systematic search of randomised controlled trials of tobacco cessation interventions in the peri-operative period. Quantitative synthesis of the abstinence outcomes data was by random-effects meta-analysis. The primary outcome of the meta-analysis was abstinence at the time of surgery, and the secondary outcome was abstinence at 12 months. Thirty-eight studies are included in the review (7310 randomised participants) and 26 studies are included in the meta-analysis (5969 randomised participants). Studies were pooled for subgroup analysis in two ways: by the timing of intervention delivery within the peri-operative period and by the intensity of the intervention protocol. We judged the quality of evidence as moderate, reflecting the degree of heterogeneity and the high risk of bias. Overall, peri-operative tobacco cessation interventions increased successful abstinence both at the time of surgery, risk ratio (95%CI) 1.48 (1.20–1.83), number needed to treat 7; and 12 months after surgery, risk ratio (95%CI) 1.62 (1.29–2.03), number needed to treat 9. More work is needed to inform the design and optimal delivery of interventions that are acceptable to patients and that can be incorporated into contemporary elective and urgent surgical pathways. Future trials should use standardised outcome measures.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Patient Blood Management in der Geburtsvorbereitung,Geburtshilfe und postpartalen Phase

Die Anaesthesiologie - Die Implementierung eines Patient Blood Management (PBM) wird zunehmender Standard in der operativen Medizin. Seit einiger Zeit gilt das Interesse auch den vulnerablen...     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.