Notes

Respiratory Transplantation and the Period from the Sensitized Patient.
Patient-reported outcomes (PROs) promote patient-centeredness in clinical trials; however, in the field of the rapidly emerging and clinically impressive immunotherapy, data on PROs are limited.

We systematically identified all immunotherapy approvals from 2011 through 2018 and assessed the analytic tools and reporting quality of associated PRO reports. For randomized clinical trials (RCTs), we developed a novel 24-point scoring scale the PRO Endpoints Analysis Score (PROEAS) based on 24 criteria derived from the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) Consortium.

We assessed 44 trial publications supporting 42 immunotherapy approvals. PROs were published for 21 of the 44 (47.7%) trial publications. Twenty-three trials (52.3%) were RCTs and 21 (47.7%) pertained to single-arm trials. The median time between primary clinical outcomes publications and their corresponding secondary PRO publications was 19 months (IQR= 9-29). Of the 21 PRO reports, 4 (19.0%) reported a specific hypothesis, and most (85.7%) used descriptive statistics. Three (3 of 21 [14.3%]) studies performed a control for type I error. As for RCTs, 14 of 23 (60.9%) published PRO data including 13 (56.5%) that published a secondary dedicated manuscript. Half of these 14 trials scored < 13 points on the 24-point PROEAS. The mean score was 12.71 (range= 5-17; SD = 3.71), and none met all the recommendations of the SISAQOL Consortium.

Suboptimal reporting of PROs occurs regularly in cancer immunotherapy trials. Increased efforts are needed to maximize the value of this data in cancer immunotherapy development and approval.
Suboptimal reporting of PROs occurs regularly in cancer immunotherapy trials. Increased efforts are needed to maximize the value of this data in cancer immunotherapy development and approval.Invertebrate animal studies of methamphetamine (METH) could allow for high throughput, inexpensive, and high-animal number pharmacology and toxicology studies. We hypothesized that in Periplaneta americana cockroaches, METH would increase locomotion compared to saline and produce lethality. Lethal dose, 50% (LD50) was determined with 0-1,780 µg/g (mg/kg) METH (n = 15-16/group) using logit analysis. Tacrolimus Locomotor activity after METH (0-560 mg/kg, intra-abdominal, n = 8 per group) administration and spontaneous locomotor activity in surviving cockroaches in an open field 24 h after LD50 study doses was measured with Noldus Ethovision. The LD50 of METH was 823.1 mg/kg (more than 10-fold greater than the value in rats). There were significant decreases in spontaneous locomotor activity in surviving cockroaches after administration of 650 and 750 mg/kg METH (P less then 0.05). While 100 mg/kg METH did not significantly increase METH locomotor activity relative to saline, 300 mg/kg METH significantly increased locomotor activity compared to saline (P less then 0.05), and 560 mg/kg METH resulted in most of the cockroaches slowly moving around the open field in the supine position for most of the trial. In conclusion, METH produces pharmacological and toxicological effects in P. americana. The high availability, low cost, and relative ease of use of these animals makes them a potential, very accessible option for studying METH use disorder.Rapid adaptation to novel environments may drive changes in genomic regions through natural selection. However, the genetic architecture underlying these adaptive changes is still poorly understood. Using population genomic approaches, we investigated the genomic architecture that underlay rapid parallel adaptation of Coilia nasus to fresh water by comparing four freshwater resident populations with their ancestral anadromous population. Linkage disequilibrium network analysis and population genetic analyses revealed two putative large chromosome inversions on LG6 and LG22, which were enriched for outlier loci and exhibited parallel association with freshwater adaptation. Drastic frequency shifts and elevated genetic differentiation were observed for the two chromosome inversions among populations, suggesting that both inversions would undergo divergent selection between anadromous and resident ecotypes. Enrichment analysis of genes within chromosome inversions showed significant enrichment of genes involved in metabolic process, immunoregulation, growth, maturation, osmoregulation, etc., which probably underlay differences in morphology, physiology and behavior between the anadromous and freshwater resident forms. The availability of beneficial standing variation, large optimum shift between marine and freshwater habitats, and high efficiency of selection with large population size could lead to the observed rapid parallel adaptive genomic change. We propose that chromosomal inversions might have played an important role during the evolution of rapid parallel ecological divergence in the face of environmental heterogeneity in C. nasus. Our study provides insights into the genomic basis of rapid adaptation of complex traits in novel habitats and highlights the importance of structural genomic variants in analyses of ecological adaptation.Cocaine consumption is associated with a variety of clinical manifestations. Though cocaine intranasal inhalation always determines nasal mucosal damages, extensive septum perforations, and midline destructions-known as cocaine-induced midline destructive lesions (CIMDL)-affect only a limited fraction of patients. CIMDL is viewed as a cocaine-associated autoimmune phenomenon in which the presence of atypical anti-neutrophil cytoplasmic antibody (ANCA) promotes and/or defines the disease phenotype. A 51-year-old man presented with an intracranial tumor-like lesion by its space-occupying effect. CT also revealed the destruction of the nasal septum and skull base. A diagnosis of CIMDL was made in light of the patient's history as well as findings of the physical and endoscopic examinations, imaging studies, and laboratory testing. There was no evidence of other pathologies. Histopathological results from cerebral biopsy led us to consider the intracranial pathology as an extension of the CIMDL. CIMDL is the result of a necrotizing inflammatory tissue response triggered by cocaine abuse in a subset of predisposed patients.
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