An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi‐quantitative clinical scores, which are not validated and may be subject to inter‐observer variability. A few previous studies suggested that high‐frequency ultrasonography (HF‐USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF‐USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF‐USG as well as dermatological assessment (target lesion score—TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non‐irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P = .0002). There was no significant difference between non‐irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF‐USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.     

CTLA4 antagonists in phase I and phase II clinical trials,current status and future perspectives for cancer therapy

Introduction: In cancer, the immune response to tumor antigens is often suppressed by inhibitors and ligands. Checkpoint blockade, considered one of the most promising frontiers for anti-cancer therapy, aims to stimulate the immune anti-cancer response. Agents such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) inhibitors offer prolonged survival with manageable side effects.

Areas covered: We summarize the recent clinical successes of CTLA-4 inhibitors and place a strong emphasis on those in early phase clinical trials, often in combination with other immune check-point inhibitors, i.e., programmed cell death protein 1 (PD-1) and BRAF/mitogen-activated protein kinase inhibitors.

Expert opinion: Recent phase I and phase II clinical trials confirm the efficacy of anti-CTLA-4 therapy for treatment of cancers such as renal cell carcinoma. These studies also indicated increased efficacy with combined immune checkpoint blockade with PD-1 or Ras/Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) inhibitors. Researchers must search for new immune targets that may enable more effective and safe immune checkpoint blockade and cancer therapy. This goal may be achieved by next-generation combination therapies to overcome immune checkpoint therapy resistance.     

Aortic pulse wave velocity and carotid-femoral pulse wave velocity: similarities and discrepancies.

The objectives of this study were to determine the relationship between carotid-femoral (cfPWV) and aortic pulse wave velocity (aPWV) and to compare their modulators and association with coronary artery disease (CAD). We studied 107 consecutive patients (68 men) with a mean age of 60.49+/-8.31 years who had stable angina and had been referred for coronary angiography. cfPWV and aPWV were measured simultaneously during cardiac catheterization using the Complior device and aortic pressure waveform recordings, respectively. Based on the presence or absence of significant coronary artery stenosis (CAS) patients were subdivided into a CAS+ or CAS- group. The mean values of cfPWV and aPWV were 10.65+/-2.29 m/s and 8.78+/-2.24 m/s, respectively. They were significantly higher in the CAS+ (n=71) compared with the CAS- (n=36) group and predicted significant CAS independently of cardiovascular risk factors and mean or systolic aortic blood pressure. aPWV and cfPWV were significantly correlated (r=0.70; p<0.001) but the degree of correlation differed significantly (p<0.03) between the CAS+ (r=0.74, p<0.001) and CAS- group (r=0.46, p=0.003). Age and mean aortic blood pressure were independent predictors for aPWV as well as cfPWV. In the receiver operating characteristic (ROC) analysis, aPWV and cfPWV had similar accuracy in identification of significant CAS (AUC [area under the ROC curve]=0.76 and 0.69, respectively; p=0.13). However, neither cfPWV nor aPWV was effective at differentiating the extent of CAD. In conclusion, aPWV and cfPWV are highly correlated parameters with similar determinants and comparable accuracy in predicting significant CAS. The strength of correlation between these two indices differed significantly between subjects with and those without CAS.     

Ethanol levels in honeybee hemolymph resulting from alcohol ingestion.

Our previous work on a social insect model of ethanol-induced behavior focused on behavioral studies of honeybees (Apis mellifera L.). We now investigate the dependence of honeybee blood ethanol concentration on both the amount of ethanol consumed and time elapsed since ingestion. Blood ethanol level was determined using gas chromatograph using hemolymph taken from harnessed bees. Significantly increased levels of ethanol in honeybee hemolymph were detected within 15 min of feeding bees alcohol. Within 30 min, ethanol concentration increased 2.7 times. The concentration of ethanol ingested also had a significant effect on blood ethanol level. However, postfeeding times greater than 30 min did not significantly increase ethanol concentration in bee hemolymph. This study integrates with our behavioral data on the effect of ethanol on honeybees. Our laboratory and field experiments show a correlation between the time frame for behavioral changes and significant increases of blood ethanol levels shown in this study.     

A treadmill test of sprint running

Anaerobic power is characterized by a high degree of specificity regarding both the recruited muscles as well as the recruitment pattern. The popular Wingate Anaerobic Test (WAnT) is a cycling test that does not satisfy the need for a running-specific anaerobic test. We describe such a test, using a novel type of a commercially available treadmill (BRL 1800, Gymrol, France). The ergometer is equipped with a torque motor to neutralize the frictional resistance of the treadmill belt, and a hip-belt harness connected to a horizontal rod. Force applied to the harness is monitored by a strain gauge mounted on the rod, while vertical movement is monitored by a potentiometer at the posterior fixed end of the rod. These, in conjunction with the treadmill belt speed, enable the computation of horizontal and vertical power as well as the combined total output. Power is calculated both as 'peak' power (highest 2.5 s segment) and 'mean' power (20 s duration). Preliminary results of young athletes were generally consistent with the expected age-related changes in anaerobic power. Values obtained on the anaerobic treadmill were always higher than the corresponding WAnT values previously obtained in comparable age groups. The higher values were probably due to the larger muscle mass involved and the shorter peak and mean power durations (2.5 and 20 s versus 5 and 30 s in the WAnT, respectively). This test should enable not only running-specific anaerobic power monitoring but also the characterization of the relationship between the horizontal and vertical components of that power.     

Changes in height of choroidal melanomas after plaque therapy.

Serial ultrasonic measurements of 82 uveal melanomas treated with brachytherapy plaques (cobalt-60 and iodine-125) and followed up for up to 141 months revealed that no two patients had identical patterns of change. The mean absolute change in tumour height after treatment was 1.8 mm at six months, 5.6 mm at 48 months for large tumours, and 0.9 and 1.9 mm for medium sized tumours. Eighty of the 82 patients fell into one of three patterns of response: 57 patients had a decrease in height after treatment (type D), 13 patients had the same height after treatment (type S), and 10 patients had a progressive increase in height (type I). Life table comparison showed no correlation between survival and location of tumour, sex of patient, size of tumour when treated, or laterality. There was a slight correlation between age and survival. Patients older than 60 died more frequently from metastatic melanoma than those under 60 (p = 0.06). Life table analysis showed a significant correlation between tumour regression type and survival. At 48 months the best cumulative probability of survival was in patients with type D (88% alive) compared with those of type I (34% alive, p = 0.0004).     

Multiple sclerosis: genetic versus environmental aetiology: epidemiology in Israel updated

The incidence and prevalence of multiple sclerosis (MS) were compared, controlling for age, in native-born Israelis of different origins and in immigrants to Israel. This comparison was carried out in two populations, countrywide and in Jerusalem. In the countrywide population, ascertainment was based mainly on hospitalizations; it included 252 patients who were native-born and 150 who had immigrated from Africa-Asia (AA immigrants). The 89 MS patients of Jerusalem also included patients diagnosed in outpatient clinics. In native-born Israelis whose father was born in Europe-America (I-EA), the incidence and prevalence of MS were found to be as high as or even higher than that found previously in immigrants from Europe-America. Among native-born Israelis whose father was born in Africa or Asia (I-AA), the yearly age-adjusted incidence and prevalence rates were found to be 1.4- to 1.8-fold higher than among AA immigrants, pointing to environmental factors. The incidence and prevalence rates in the I-EA were 1.2- to 1.6-fold higher than in the I-AA, pointing to genetic factors. These results seem to point to both environmental and genetic factors in the aetiology of MS. Further research is needed, however, to disentangle the genetic factors from possible environmental differences in the two ethnic groups.