Search

Abstract Desmoplasia is characteristic of pancreatic ductal adenocarcinoma (PDAC), which exhibits 5‐year survival rates of 3%. Desmoplasia presents physical and biochemical barriers that contribute to treatment resistance, yet depleting the stroma alone is unsuccessful and even detrimental to patient outcomes. This study is the first demonstration of targeted photoactivable multi‐inhibitor liposomes (TPMILs) that induce both photodynamic and chemotherapeutic tumor insult, while simultaneously remediating desmoplasia in orthotopic PDAC. TPMILs targeted with cetuximab (anti‐EGFR mAb) contain lipidated benzoporphyrin derivative (BPD‐PC) photosensitizer and irinotecan. The desmoplastic tumors comprise human PDAC cells and patient‐derived cancer‐associated fibroblasts. Upon photoactivation, the TPMILs induce 90% tumor growth inhibition at only 8.1% of the patient equivalent dose of nanoliposomal irinotecan (nal‐IRI). Without EGFR targeting, PMIL photoactivation is ineffective. TPMIL photoactivation is also sixfold more effective at inhibiting tumor growth than a cocktail of Visudyne‐photodynamic therapy (PDT) and nal‐IRI, and also doubles survival and extends progression‐free survival by greater than fivefold. Second harmonic generation imaging reveals that TPMIL photoactivation reduces collagen density by >90% and increases collagen nonalignment by >103‐fold. Collagen nonalignment correlates with a reduction in tumor burden and survival. This single‐construct phototoxic, chemotherapeutic, and desmoplasia‐remediating regimen offers unprecedented opportunities to substantially extend survival in patients with otherwise dismal prognoses.

The use of microcatheters as a coronary interventional tool for a therapeutic approach to complex coronary interventions like bifurcation lesions, ostial location, tortuous anatomy, angled takeoffs, coronary calcification, and chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is growing among cardiologists across the country. During the treatment of such complex lesions, microcatheters play an essential part of the tool kit with both single-lumen and double-lumen microcatheters (DLMs) having their specific niche areas. The selection of microcatheters involves a detailed understanding of the microcatheter specification, lesion anatomy, lesion location, vessel tortuosity and trajectory, and crossing techniques. The selection of appropriate crossing techniques with different microcatheters increases success rates of PCI, reduces procedural time and contrast use, and lowers the radiation. However, the use of microcatheters and their technicalities have not yet fully realized by many operators and their true scope has not been fully explored. This article discusses and summarizes the thoughts and key opinions of experts in this field.

Abstract Background There is an increasing concern over adolescent concussions in sports due to risks of long-term negative effects. This study analyzed data over three school years on reported concussion incidence rates by season, high school grade levels and gender, and reported symptoms by school nurses versus athletic trainers, from New Jersey student-athlete concussion data available from an online school-based surveillance system. Methods School nurses and athletic trainers reported 300 concussions within five days from when each occurred over three school years, 2015–2018, in team sports and physical education in New Jersey high schools. Analysis was further conducted on symptoms and number of symptoms reported by school nurses versus school athletic trainers for each documented student-athlete concussion. Estimated concussion incidence rates were calculated using state agency verified school enrollment data. Findings Concussions most commonly occurred during fall, followed by spring, then winter. Concussion incidence rates ranged from 6.3/1000 (4.99, 7.55) – 9.1/1000 (7.27, 10.98) students over the three school years of the study. Athletic trainers completed 86% of the reports while nurses completed 11% (position or title of 3%, or n = 7, were not disclosed); the values were similar when considering only fall pre-season and regular season sports (88, 10, 2%, respectively). On average, across the three school years, athletic trainers reported about 3.5 symptoms per report while nurses reported 2.7 (values in fall seasons only were 3.7 and 3.1, respectively.) Conclusions Certified athletic trainers, compared to school nurses, more often completed concussion report forms and reported more symptoms per injured student, perhaps due partly to closer contact and immediate care provided after injury. Additionally, this study had a higher concussion incidence rate during fall sports seasons compared to winter and spring. Future research can further improve our understanding of concussions among adolescent student-athletes to better inform concussion identification, management and recovery protocols.

The emergence of biomimetic nanotechnology has seen an exponential rise over the past decade with applications in regenerative medicine, immunotherapy and drug delivery. In the context of nanomedicines activated by near infrared (NIR) photodynamic processes (photonanomedicines; PNMs), biomimetic nanotechnology is pushing the boundaries of activatable tumor targeted nanoscale drug delivery systems. This review discusses how, by harnessing a unique collective of biological processes critical to targeting of solid tumors, biomimetic PNMs (bPNMs) can impart tumor cell specific and tumor selective photodynamic therapy-based combination regimens. Through molecular immune evasion and self-recognition, bPNMs can confer both tumor selectivity (preferential bulk tumor accumulation) and tumor specificity (discrete molecular affinity for cancer cells), respectively. They do so in a manner that is akin, yet arguably superior, to synthetic molecular-targeted PNMs. A particular emphasis is made on how bPNMs can be engineered to circumvent tumor cell heterogeneity, which is considered the Achilles’ heel of molecular targeted therapeutics. Forward-looking propositions are also presented on how patient tumor heterogeneity can ultimately be recapitulated to fabricate patient-specific, heterogeneity-targeting bPNMs.