Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.     

Impact of 970 nm photobiomodulation therapy on wound healing in cellular models of hidradenitis suppurativa

Lasers in Medical Science -     

Cross-Cultural Adaptation and Validation of the Pain Scale for Plantar Fasciitis to Spanish

The aim of this study was the validation and transcultural adaptation of the Pain Scale for Plantar Fasciitis to Spanish, following the steps defined by “Guidelines for the process of cross-cultural adaptation of self-report measures.” A cross-sectional study was driven in 153 patients with unilateral plantar fasciitis diagnosis. Statistical analysis measured the internal consistency, the test-retest reliability, the construct validity with the Spanish version of Foot and Function Index, and a factorial analysis. The questionnaire Pain Scale for Plantar Fasciitis was also given to a group of 10 people who received a physiotherapy treatment based on manual therapy, therapeutic exercise, and health education, which aim was to determine the questionnaire's sensitivity to changes. The questionnaire showed high internal consistency and test-retest reliability (Cronbach's α = 0.99, intraclass correlation coefficient = 0.98 [0.97-0.98]), good convergent validity with a moderate correlation with the Foot and Function Index (rho = 0.677, p < .0001) and no floor or ceiling effects were detected. The factorial analysis revealed that the first 3 factors showed 42.47% of variance, finding only 1 latent feature. Statistically significant differences were found in those patients who received physiotherapy treatment after 1 month, revealing that the questionnaire was sensitive to changes in the symptoms of subjects with plantar fasciitis. The Spanish version of Pain Scale for Plantar Fasciitis has proved to be a valid, reliable, and change-sensitive tool for patients with plantar fasciitis.     

Synergy of the Tropical Earthworm Pontoscolex corethrurus and Oil Palm Bagasse in the Removal of Heavy Crude Oil

The tropical endogeic earthworm Pontoscolex corethrurus, a non-standard species used in ecotoxicity, has been found in crude oil-contaminated habitats. We estimated the removal of total hydrocarbons from heavy crude “Maya” oil on an artificially contaminated soil with a median lethal concentration of P. corethrurus and an addition of oil palm bagasse. P. corethrurus had a high survival rate, and the addition of oil palm bagasse led to a greater growth and an increase in abundance of bacteria and fungi. The activity of P. corethrurus and the nutritional quality of oil palm bagasse had a significant impact on the removal of a larger amount of petroleum hydrocarbons from contaminated soil. We concluded that the endogeic earthworm P. corethrurus and oil palm bagasse acted synergistically to achieve a more effective removal of total petroleum hydrocarbons from soil. These results show the potential for using P. corethrurus to remove, either directly or indirectly, crude oil from soil.

     

On the need of a sampling strategy in biological monitoring: The example of hexane exposure

Ambient and biological monitoring of hexane exposure were repeatedly carried out in 14 female shoe makers. Airborne hexane (Ci-H) was measured in 4-h samples collected by a diffusive method. Urinary spot samples were collected before, during (at noon), and at the end of a work shift. 2,5-Hexanedione (2,5HD) in urine collected at noon was poorly related to morning Ci-H. End-of-shift 2,5HD were also poorly related to afternoon air samples. The correlation was still relatively low when end-of-shift 2,5HD was related to 8-h TWA Ci-H (r= 0.44; P<0.01 on=" a=" linear=" scale,=" and=">r-0.58, P< 0.01=" on=" a=" log-log=" scale).=" end-of-shift=" 2,5hd=" levels=" estimated=" on=" the=" basis=" of=" pre-shift=" values=" using=" a=" mathematical=" model=" were=" much=" higher=" (2.3=" times=" on=" average)=" than=" those=" experimentally=" measured=" during=" the=" study=" period.=" owing=" to=" its=" relatively=" long=" half-time,=" 2,5hd=" seems=" to=" be=" influenced=" not=" only=" by=" current=" exposure,=" but=" also=" by=" hexane=" absorbed=" during=" the=" day(s)=" preceding=" sampling.=" the=" lack=" of=" a=" sampling=" strategy=" may=" account=" not=" only=" for=" inconsistencies=" between=" environmental=" and=" biological=" data,=" but=" also=" for=" a=" possible=" misuse=" of=" biological=" monitoring=" when=" utilized=" for=" risk=" assessment.=" despite=" sometimes=" poor=" correlations=" with=" ci-h,=" 2,5hd=" may=" still=" be=" preferred=" to=" other=" indicators=" as=" a=" marker=" of=" effective=" internal=" dose.=" a=" sampling=" strategy=" should=" ensure=" that=" measured=" values=" are=" representative=" of=" the=" individual=" risk=" for=" adverse=">     

Involvement of cholecystokinin receptors in the control of striatal dopamine autoreceptors

Summary The interaction of locally perfused cholecystokinin-8 (sulphated) with systemically administered apomorphine was studied on the release of dopamine and its metabolites using microdialysis in the neostriatum of the halothane-anaesthetized male rat. Dialysate levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were assayed by high performance liquid chromatography in combination with electrochemical detection. Perfusion with cholecystokinin-8 (100 M but not 1 M or 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC or HVA. At low concentrations (1 M and 10 nM but not 1 nM), cholecystokinin-8 counteracted the inhibitory effect of apomorphine (0.05 mg/kg, s. c.) on dopamine release. This counteraction was antagonized by perfusion with the cholecystokinin-8 antagonist proglumide (3 M). At this concentration, proglumide perfused alone was without effect on basal or apomorphine-reduced levels of dopamine. The results indicate a facilitatory effect of cholecystokinin-8 on dopamine release in rat neostriatum only at high concentrations. At lower concentrations, cholecystokinin-8 appears to modulate dopamine release by an inhibitory effect on dopamine autoreceptors possibly involving an intramembrane interaction between presynaptic cholecystokinin-8 receptors and dopamine autoreceptors. Send offprint requests to K. Fuxe at the above address