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.     

COVID-19 and mental health: a longitudinal population study from Norway

European Journal of Epidemiology - Existing research has found adverse short-term effects of the COVID-19 pandemic on mental health, but longer-term effects have been less documented. Using newly...     

Clinical presentation of young people (10–24 years old) with brain tumors: results from the international MOBI-Kids study

Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in...     

Effects of ambient particulate matter on vascular tissue: a review

ABSTRACT

Fine and ultra-fine particulate matter (PM) are major constituents of urban air pollution and recognized risk factors for cardiovascular diseases. This review examined the effects of PM exposure on vascular tissue. Specific mechanisms by which PM affects the vasculature include inflammation, oxidative stress, actions on vascular tone and vasomotor responses, as well as atherosclerotic plaque formation. Further, there appears to be a greater PM exposure effect on susceptible individuals with pre-existing cardiovascular conditions.     

Free Bipedicled Radial Forearm and Posterior Interosseous Artery Perforator Flap Phalloplasty

IntroductionThe free radial forearm (FRFA) flap is universally still considered as the gold standard technique in penile reconstruction. Typically, a considerably large flap is required, often involving almost the entire circumference of the forearm. Partial necrosis may occur at the distal-most (dorsoradial) part of the flap as a result of insufficient perfusion.AimTo describe a new technique using the posterior interosseous artery (PIOA) to supercharge FRFA phalloplasty.MethodsIn a 12-month period, all patients having FRFA flap phalloplasty were enrolled. Perioperative, after complete flap dissection, an indocyanine green perfusion scan was performed. In case of insufficient perfusion at the distalmost part of the flap, a supramicrosurgical anastomosis was performed between the FRFA pedicle and the PIOA (artery only).Main Outcome MeasuresStudied outcomes included the rate of marginal necrosis, surgical time, postoperative posterior interosseous nerve damage and urethral complications (fistula, stenosis or necrosis).ResultsA total of 27 FRFA flap phalloplasties was performed. Anastomosis of the PIOA was needed in 15 cases. No marginal necrosis was observed in these cases. There were no cases of postoperative posterior interosseous nerve damage. There were no significant differences in urethral complications (fistula, stenosis or necrosis) between the 2 groups.Clinical ImplicationsIn selected cases where insufficient perfusion of the dorsoradial part of the flap is present, patients may benefit from arterial supercharging to prevent postoperative marginal necrosis.Strength & LimitationsStrengths include a single surgeon, thus lending continuity of skill and technique, a consecutive series, and 100% short-term follow-up. Limitations include single institution series and a limited number of patients.ConclusionArterial supercharging is effective in improving perfusion of large FRFA flaps used in phalloplasty when dorsoradial hypoperfusion is detected on an indocyanine green perfusion scan. It is a technically challenging addition to the standard technique because of the small size of the vessels, the close relationship between the PIOA and the posterior interosseous nerve, and the vulnerability of the newly constructed intra-flap anastomosis.De Wolf E, Claes K, Sommeling CE, et al. Free Bipedicled Radial Forearm and Posterior Interosseous Artery Perforator Flap Phalloplasty. J Sex Med 2019;16:1111–1117.     

Bone mineral density,bone turnover markers,and incident fractures in de novo kidney transplant recipients

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Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 2: Alcohol-Associated Osteonecrosis

Background

Although alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH) and its prevalence reportedly ranges from 20% to 45%, there are no unified classification criteria for this subpopulation. In 2015, Association Research Circulation Osseous decided to develop classification criteria for alcohol-associated ONFH.