Reference values for radial bone width and mineral content using single photon absorptiometry in healthy children aged 4 to 10 years

Bone width and mineral content were measured in 420 healthy Cambridge children aged 4 to 10 years using single photon absorptiometry. The results are expressed first in the form of standard centile charts, with additional prediction charts which provide body-size-adjusted estimates for the measurements, and interpretation centiles for comparing these estimates with the actual measurements. The values obtained are similar to those reported for American children aged five to six years after adjusting for body-size differences. We suggest that appropriate application of these prediction charts will facilitate the use of single photon absorptiometry in monitoring and treating children who have disorders of bone growth and mineralization.     

Trends in Checkpoint Inhibitor Therapy for Advanced Urothelial Cell Carcinoma at the End of Life: Insights from Real-World Practice

Several immune checkpoint inhibitor therapies (CPIs) have been approved to treat metastatic urothelial cell carcinoma (mUC). Because of the favorable toxicity profile of CPI compared with chemotherapy, oncologists may have a low threshold to prescribe CPI to patients near the end of life. We evaluated trends in initiation of end-of-life systemic therapy in 1,637 individuals in the Flatiron Health Database who were diagnosed with mUC between 2015 and 2017 and who died. Rates of systemic therapy initiation in the last 30 and 60 days of life were 17.0% and 29.8%, respectively. The quarterly proportion of patients who initiated CPI within 60 days of death increased from 1.0% to 23% during the study period (p_trend < .001). After CPI approval, end-of-life CPI initiation significantly increased among patients with poor performance status (p_trend = .020) and did not significantly change among individuals with good performance status. The quarterly proportion of patients who initiated any systemic therapy at the end of life doubled (17.4% to 34.8%) during the study period, largely explained by increased CPI use. These findings suggest a dramatic rise in CPI use at the end of life in patients with mUC, a finding that may have important guideline and policy implications.     

Women at increased risk for cardiac toxicity following chemoradiation therapy for esophageal carcinoma

PurposeThe purpose of this study was to identify factors associated with cardiac toxicity in patients treated with chemoradiation therapy (CRT) for esophageal carcinoma.Methods and MaterialsOne hundred twenty-seven patients with adenocarcinoma or squamous cell carcinoma of the esophagus treated from July 2002 to June 2011 at 2 academic institutions with preoperative or definitive CRT were retrospectively reviewed. Association of cardiac toxicity with a number of variables was investigated, including heart disease, cardiac bypass and angioplasty, diabetes, insulin use, smoking, chemotherapy regimen, and tumor location. T test assessed risk of cardiac toxicity secondary to age. Dose volume histograms (DVH) were evaluated for percentage of heart volume receiving > 20, 30, 40, and 50 Gy (V20-V50). The Fisher exact test analyzed for an association between dose volume parameters and cardiac toxicity.ResultsPatient population included 100 men and 27 women with a mean age of 64 years. Median follow-up was 12.7 months (range, 0.3-99.6 months). Any cardiac toxicity occurred in 28 patients, the majority of which were pericardial effusion (23/28). Odds ratio for toxicity in women was 4.15 (95% confidence interval [CI], 1.63-10.50; P = .0017) and time to cardiac toxicity by sex was significant (P = .0003). Patients above the median cutoff for V20, V30, and V40 had increased odds of developing cardiac toxicity (P = .03, .008, .002). There was 4.0 increased odds of developing cardiac toxicity with V40 > 57% (95% CI, 1.5-10.3, P = .002). On multivariable logistic regression analysis, sex was the only variable associated with any cardiac toxicity and pericardial effusion (P = .0016, P = .0038). None of the other investigated variables were associated with increased risk of cardiac toxicity.ConclusionsFemale patients and dose greater than the median for V20-V40 were associated with the development of cardiac toxicity, specifically pericardial effusion. These data suggest exercising increased care when designing radiation fields in women undergoing CRT for esophageal carcinoma, as pericardial effusion may be a long-term complication.     

An internet method to assess cancer patient information needs and enhance doctor-patient communication: A pilot study

BACKGROUND: We previously reported that doctor-patient communication in the cancer context may be suboptimal. We therefore developed measures to assess patient communication preferences and established feasibility of an Internet-based intervention to improve communication. METHODS: Cancer patients completed an Internet-based survey about communication preferences, with a summary provided to the physician before the consultation. Patients completed a follow-up survey to assess consultation content and satisfaction. RESULTS: Study procedures were feasible, measures exhibited strong internal consistency, and patients expressed satisfaction with the intervention. CONCLUSION: The Internet offers an opportunity to assess patient preferences and prompt physicians about individual patient informational needs prior to the clinical encounter.     

Atrial septal defects: Magnetic resonance and computed tomography appearances

Atrial septal defects are associated with significant morbidity and mortality. Echocardiography is the first‐line imaging modality, but MR and CT imaging can provide complimentary information, especially for the detection of associated anomalies and for assessing changes in the pulmonary vasculature. The aim of this pictorial essay is to review the spectrum of atrial septal defects, with particular reference to their cross‐sectional imaging appearances and issues pertaining to management.     

Introductory comment

Objectives Injectable poly‐l ‐lactic acid (PLLA; Sculptra^®) is widely used throughout Europe and the USA to restore volume in depressed areas of the face by stimulating neocollagenesis. Injectable PLLA was previously marketed as New‐Fill™, which was often injected incorrectly and at too high a concentration, resulting in some physicians losing confidence in this product. Today, Sculptra^® is still regarded with a degree of scepticism by some physicians, due to direct or indirect experience with New‐Fill. Sculptra^®, both in formulation and use, is vastly superior to New‐Fill and clinical experience with this product dispels the myths associated with the earlier types of injectable PLLA. Results PLLA is a very safe, biodegradable compound that has been used in a wide range of medical devices for the last 30 years. In injectable form a good safety profile has been proven; however, when the device is overconcentrated, localized overstimulation of the fibroblasts can result in the formation of small lumps (subcutaneous papules), which are non‐pathological but nevertheless palpable by the patient. Physicians must also be trained in the injection of this device, as incorrect injection technique can cause device‐related adverse events. Conclusion New product guidelines have ensured that problems with PLLA concentration have been countered, and tried and tested injection techniques have been shown to ameliorate device‐related adverse events, both of which are dispelling the myths associated with modern injectable PLLA.     

LYMPHANGIOMA PRESENTING AS A NECK MASS IN THE ADULT

Lymphangiomas are uncommon congenital lesions of the lymphatic system which usually present in childhood. We report a case of adult lymphangioma, localised in the neck, and discuss the presentation, diagnosis and management of this tumour.     

Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation,Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH⁺) and microglia markers (Iba-1⁺; CD68⁺) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68⁺/ Iba-1⁺ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.