Key points• Heating human skin results in a localized increase in blood flow (hyperaemia) to the skin.• Experiments in mouse skin and cultured human cells suggest that skin cells known as keratinocytes release the chemical ATP, a known cutaneous vasodilator, and that the release of this ATP increases when temperature-sensing vanilloid type III and IV transient receptor potential ion channels (TRPV3, TRPV4 respectively) are activated by heating. Studies also suggest that this ATP release is necessary for temperature sensation.• We hypothesized that, like mouse skin locally heating human skin to temperatures that activate heat-sensing TRPV3 and TRPV4 channels would be associated with an accumulation of ATP in the interstitial space that would be related to temperature sensation.• We also hypothesized that the accumulation of ATP would be associated with the magnitude of heat-induced hyperaemia to the area.• We report that, unlike mouse skin, such local heating does not result in an accumulation of ATP in the interstitial space of human skin, and therefore such an accumulation is not necessary for cutaneous temperature sensation and local reactive hyperaemia.• We also report that warming skin from 31• C results in dilatation at temperatures as low as 35• C, which is several degrees lower than previously reported. This suggests that TRPV3 and/or TRPV4 channels have a role in heat-induced hyperaemia or that such heating sensitizes TRPV1 channels to respond to temperatures below their typical threshold.Abstract Heating skin is believed to activate vanilloid type III and IV transient receptor potential ion channels (TRPV3, TRPV4, respectively), resulting in the release of ATP into the interstitial fluid. We examined the hypothesis that local skin heating would result in an accumulation of ATP in the interstitial fluid that would be related with a rise in skin blood flow (SkBF) and temperature sensation. Two microdialysis probes were inserted into the dermis on the dorsal aspect of the forearm in 15 young, healthy subjects. The probed skin was maintained at 31• C, 35• C, 39• C and 43• C for 8 min periods, during which SkBF was monitored as cutaneous vascular conductance (CVC). Dialysate was collected and analysed for ATP ([ATP] d ) using a luciferase-based assay, and ratings of perceived warmth were taken at each temperature. At a skin temperature of 31• C, [ATP] d averaged 18.93 ± 4.06 nM and CVC averaged 12.57 ± 1.59% peak. Heating skin to 35• C resulted in an increase in CVC (17.63 ± 1.27% peak; P < 0.05), but no change in [ATP] d . Heating skin to 39• C and 43• C resulted in a decreased [ATP] d (5.88 ± 1.68 nM and 8.75 ± 3.44 nM, respectively; P < 0.05), which was accompanied by significant elevations in CVC (38.90 ± 1.37% peak and 60.32 ± 1.95% peak, respectively; P < 0.05). Ratings of perceived warmth increased in proportion to the increase in skin temperature (r 2 = 0.75, P < 0.05). In conclusion, our data indicate that an accumulation of interstitial ATP does not occur during local heating, and therefore does no...

IntroductionStereotactic ablative body radiotherapy (SABR) provides a superior non-small cell lung cancer (NSCLC) treatment option when compared to conventional radiotherapy for patients deemed inoperable or refusing surgery. This study retrospectively analyzed the rates of tumor control and toxicity following SABR treatment (Cyberknife system) of primary early-stage NSCLC in a community setting.MethodsOne hundred patients were treated between 2007 and 2011. Patients with T3-4 or N1-3 disease, metastasis, recurrent local disease, or a non-lung primary were excluded from analysis. All patients had biopsy proven disease. Staging included CT or fluorodeoxyglucose-positron emission tomography scan. Median dose was 54 Gy (45–60); 18 Gy (10–20) per fraction. Median planned target volume expansion was 8 mm (2–10). Median BED was 151.2. Tumors were tracked via Synchrony, X-Sight Lung, or X-Sight Spine. Patients were evaluated for local control, overall survival (OS), and toxicity. All local failures were determined by evaluating post treatment PET/CT.ResultsWith a median follow up of 27.5 months, the 1-, 2-, and 3-year local control rates were 100, 93.55, and 84.33%, respectively. Median survival was 2.29 years; actuarial 3-year survival was 37.20%. Grade-3 toxicity was observed in 2% of patients (pneumonia within 2 months of treatment, n = 1; chronic pneumonitis requiring hospital admission, n = 1). No patients demonstrated toxicity above Grade-3. Multivariate analysis did not show T-stage as an independent predictor of OS, though it did trend toward significance.ConclusionIn a community-center setting, definitive treatment of NSCLC with SABR for non-surgical candidates and those who choose to forego surgery result in excellent and comparable rates of local control and toxicity compared to published series from large academic centers.

ObjectiveThe objective of the present study is to analyze prognostic factors affecting survival of patients receiving stereotactic radiosurgery (SRS) for second brain metastatic event (SBME) following initial treatment with whole brain irradiation (WBI), surgical resection, or previous SRS.MethodsThe 88 patients treated with SRS for SBME at Philadelphia CyberKnife between January 2006 and October 2013 were included in the study group. Cox proportional-hazards regression was used to identify prognostic factors that significantly impacted survival from the time of SRS for SBME. Independent variables considered in survival analysis included primary disease, first brain metastatic event (FBME) treatment type, age, gender, number of brain metastases at SBME, Karnofsky performance status (KPS), recursive partitioning analysis (RPA), and presence of extracranial metastasis.ResultsThe median survival for all patients was 7.31 months. Log-rank comparison of Kaplan-Meier survival curves revealed significant impact by Karnofsky performance status (p = 0.003), RPA class (p = 0.008), age (p = 0.014), and FBME treatment type (p = 0.010). Median survival was longer for patients who had not previously received WBI (14.7 months). Median survival was further increased in patients who had not received previous WBI and demonstrated KPS scores of 70–100 (19.5 months). Patients who received WBI prior to SBME treatment experienced a pronounced decrement in median survival (5.7 months), yet patients in this group who demonstrated strong KPS scores (80–100) experienced significantly increased survival (15.5 months).ConclusionsThe outcomes of SRS for SBME are most favorable for patients who have not received previous WBI or who have maintained higher performance status despite previous WBI.

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variables and ESAS scores were analyzed using the Mann Whitney U test and correlations between variables were calculated by Kendall's tau-b tests.Results: 87 patients with EsoCa completed ESAS between 2/16 2017 and 7/ 21 2019. Of these patients, 44 completed 3 ESAS surveys (median Z 5, mean 5.7, range 3-12) while on treatment and form the cohort further analyzed. In this cohort, the majority were men (77.3%, nZ34) and white/ Caucasian (nZ95.5%, nZ42). Seven (16%) patients had cervical esophageal lesions, four (9%) had middle lesions and 33 (75%) had distal lesions. The majority of patients had adenocarcinoma (75%, nZ33). The ESAS item with the highest median score was tiredness (4.25) with a median total score of 19.75. Patients with middle lesions were more likely to experience pain (4.25 v. 0.25, pZ0.028) and drowsiness (2.5 v. 0, pZ0.017), but no statistically significant relationships were seen for those with distal or cervical lesions. Patients with squamous cell carcinoma were more likely to experience anxiety (3 v. 0, pZ0.047), although this may represent a statistical aberration. The strongest correlation between symptoms were found between depression and spiritual pain (tb 0.609, pZ0.000). Drowsiness was correlated with the most symptoms, including shortness of breath (0.346, pZ0.0090), pain (0.447, pZ0.000), tiredness (0.344, pZ0.005), nausea (0.424, pZ0.001), depression (0.363, pZ0.007), and insomnia (0.323, pZ0.009). Conclusions: In this large analysis of PRO in EsoCa, patients with middle esophageal lesions were more likely to experience pain and drowsiness, while those with squamous cell carcinoma reported more anxiety. Uncontrolled esophageal pain could lead to unanticipated interval hospitalizations or IV fluid interventions so further analysis with large PRO libraries is indicated to validate these findings.