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Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following postoperative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in situ tissue-conforming and tissue-adherent scaffolds with exceptional mechanical properties. While biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) have desirable strength, they exhibit bulk biodegradation rates and inflammatory profiles that limit their use as adhesion barriers and result in poor tissue adhesion. Here, viscoelastic poly(lactide-co-caprolactone) (PLCL) is used for its pertinent biodegradation mechanism. Because it degrades via surface erosion, spray deposited PLCL fibers can dissolve new connections formed by inflamed tissue, allowing them to function as an effective, durable, and easy-to-apply adhesion barrier. Degradation kinetics are tuned to match adhesion formation through the design of PLCL blends comprised of highly adhesive "low"-molecular weight (LMW) constituents in a mechanically robust "high"-molecular weight (HMW) matrix. In vitro studies demonstrate that blending LMW PLCL (30% w/v) with HMW PLCL (70% w/v) yields an anti-fibrotic yet tissue-adhesive polymer sealant with a 14-day erosion rate countering adhesion formation. PLCL blends additionally exhibit improved wet tissue adhesion strength (~10 kPa) over a 14-day period versus previously explored biodegradable polymer compositions, such as PLGA. In a mouse cecal ligation model, select PLCL blends significantly reduce abdominal adhesions severity versus no treatment and Seprafilm-treated controls. [ABSTRACT FROM AUTHOR]

Background Adaptive immune resistance induces an immunosuppressive tumor environment that enables immune evasion. This phenomenon results in tumor escape with progression and metastasis. Programmed cell death-ligand 1 (PD-L1) expressed on tumors is thought to inhibit tumor-infiltrating lymphocytes (TILs) through programmed cell death 1 (PD1), enabling adaptive immune resistance. This study investigates the role of PD-L1 in both mouse and human neuroblastoma immunity. The consequence of PD-L1 inhibition is characterized in the context of an established whole tumor cell vaccine. Methods and findings A mouse model of neuroblastoma was investigated using an Id2 knockdown whole cell vaccine in combination with checkpoint inhibition. We show that immunogenic mouse neuroblastoma acquires adaptive immune resistance by up-regulating PD-L1 expression, whereas PD-L1 is of lesser consequence in nonimmunogenic neuroblastoma tumors. Combining PD-L1 checkpoint inhibition with whole tumor cell/anti-CTLA-4 vaccination enhanced tumor cell killing, cured mice with established tumors, and induced long-term immune memory (6 months). From an evaluation of patient neuroblastoma tumors, we found that the inflammatory environment of the mouse neuroblastoma mimicked human disease in which PD-L1 expression was associated directly with TILs and lower-risk tumors. High-risk patient tumors were lacking both TILs and PD-L1 expression. Although a correlation in immunity seems to exist between the mouse model and human findings, the mouse tumor model is induced and not spontaneously occurring, and furthermore, the number of both mouse and human correlates is limited. Conclusions This study demonstrates the role PD-L1 plays in neuroblastoma's resistance to immunity and defines the nonredundant effect of combination checkpoint inhibition with vaccine therapy in a mouse model. High-risk, nonimmunogenic human tumors display both diminished PD-L1 expression and adaptive immune resistance. Paradoxically, high-risk tumors may be more responsive to effective vaccine therapy because of their apparent lack of adaptive immune resistance., Author(s): Priya Srinivasan, Xiaofang Wu, Mousumi Basu, Christopher Rossi, Anthony D. Sandler * Introduction Neuroblastoma is the most common extracranial solid tumor found in children and continues to have a [...]

Introduction: Tracheal agenesis (TA) is rare and usually fatal. Few survivors with concomitant tracheoesophageal fistulae (TEF) who underwent ligation of the distal esophagus with creation of a spit-fistula and neo-trachea from the proximal esophagus exist. We report a novel surgical technique whereby the esophagus is divided longitudinally to preserve a functional alimentation tract and a parallel neo-trachea. We review the literature of reported cases, including survivors beyond 12 months. Methods: Case report and literature review. Results: A female infant with prenatal polyhydramnios was born at 35 weeks gestation with immediate respiratory distress and absent cry. Oxygenation was maintained with a laryngeal mask airway. Despite a normal appearing larynx, she could not be intubated and emergent neck exploration disclosed no cervical trachea. The patient was placed on extra corporeal membranous oxygenation (ECMO), and later diagnosed with TA, Floyd Type I. Parental desire for reconstruction but refusal of a spit-fistula necessitated a novel procedure. The esophagus was divided longitudinally via a microstapler to preserve the original alimentary tract and create a parallel neo-trachea originating from the TEF and terminating as a cervical stoma. The healing process was complicated but the baby was ultimately discharged to home where she developed normally neurologically until succumbing one night to accidental decannulation at 16 months of age. Conclusion: We describe a novel surgical approach to manage TA. This includes avoiding creation of a spit fistula and preserving the native esophagus. We then survey the literature, reporting the survivorship duration and operative management of 174 reported cases of TA. [ABSTRACT FROM AUTHOR]

Background Necrotizing enterocolitis (NEC) is a complication of prematurity with a high mortality rate. Currently, there are no reliable biomarkers capable of identifying infants at risk for developing NEC. We sought to determine the autonomic nervous system antecedents of NEC in premature infants, using heart rate variability (HRV). Materials and Methods HRV was quantified by retrieving archived electrocardiogram (EKG) data from 30 premature infants from 4 days prior, through 4 days after, the clinical NEC diagnosis. HRV metrics were compared with those on the diagnosis day using the receiver operating characteristic (ROC) analysis. Results HRV metrics showed a depression of autonomic tone that preceded the clinical NEC diagnosis by 2 days, and which recovered to baseline by 2 days after diagnosis (area under the curve [AUC] < 0.7). The pattern of HRV change was significantly associated with the clinical severity of NEC (stage II vs. stage III). Conclusion Our studies suggest that readily accessible metrics of autonomic depression might expedite the diagnosis of NEC and its severity in a clinically meaningful manner. Clearly, these studies need to be extended prospectively to determine the diagnostic utility of this approach. [ABSTRACT FROM AUTHOR]