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There is a growing body of literature regarding long-term pulmonary outcomes in children with congenital diaphragmatic hernia (CDH). Oral feeding skills in these children are often delayed. CRCD2 Chronic descending aspiration due to uncoordinated swallowing can further insult the already compromised lung parenchyma in these children. This study describes patterns of swallowing dysfunction and aspiration in patients with CDH.

Records of all children treated for CDH at our institution from January 2014 to December 2019 were reviewed. Concern for swallowing dysfunction was marked by performance of a video-fluoroscopic swallow study (VFSS). We determined the frequency of aspiration on VFSS and how frequently that finding changed patient management. We also evaluated for association between clinical suspicion of swallow dysfunction and descriptors of CDH severity.

Sixty-nine patients were treated during this 6-year time period. Of those, 10 (14%) had a VFSS as an inpatient, and 25 (36%) had one as an outpatient. Eight (80%) inpatient and 17 (68%) outpatient studies identified aspiration. VFSS results changed management in 80% of patients, often by altering the consistency of oral feeds. There were no associations between CDH side, defect size or need for a patch and need for a VFSS.

The frequency of aspiration in the CDH population is high. Identification of aspiration on VFSS leads to changes in treatment aimed at protecting the lungs. Additionally, the severity of the CDH was not associated with aspiration on VFSS.
The frequency of aspiration in the CDH population is high. Identification of aspiration on VFSS leads to changes in treatment aimed at protecting the lungs. Additionally, the severity of the CDH was not associated with aspiration on VFSS.
In the US, opioids are overprescribed after surgery contributing to the opioid epidemic. Patients' expectations regarding postoperative opioids remains unclear.

A representative survey using random-digit dial telephone sampling of English-speaking adults in US was conducted from August 28 to December 11, 2019.

Of the 1533 eligible persons contacted, 1000 completed the interviews yielding a cooperation rate of 65%. The mean age was 47 (±18) years, half were men, and most were non-Hispanic white (73%). Forty-eight percent expected an opioid prescription after major surgery, 50% worry about addiction, and 61% believe they contribute to the opioid epidemic. Interestingly, 31% assume that opioid-dependent users were first exposed to opioids following surgery.

Many Americans surveyed expect to receive an opioid containing pain medication after major surgery, but fear the risk of addiction and believe that they are contributing to the opioid epidemic. They do not think that opioid-dependent users were first exposed to opioids after surgery. This discordance may represent an area of policy action and education.
Many Americans surveyed expect to receive an opioid containing pain medication after major surgery, but fear the risk of addiction and believe that they are contributing to the opioid epidemic. They do not think that opioid-dependent users were first exposed to opioids after surgery. This discordance may represent an area of policy action and education.Therapies for glioblastoma face several physiologic hurdles. link2 The blood-brain barrier (BBB) and blood-brain-tumor barrier (BTB) present impediments to therapeutic delivery of drugs to the central nervous system. Strategies to disrupt or bypass the native BBB are necessary to deliver therapeutic agents. Techniques to bypass the BBB/BTB include implantable controlled-release polymer systems, intracavitary drug delivery, direct injection of viral vectors, and infusion via convection-enhanced delivery. Ideal methods and agents to accomplish the goal providing survival benefit are yet to be determined. Further development of methods to break down or bypass the BBB and BTB is necessary for patients with glioblastoma.Only a small fraction of the tumor cell population, glioma-initiating cells (GICs) help glioblastoma propagate, invade, evade immune recognition, repair DNA in response to radiation more efficiently, remodel the microenvironment for optimal growth, and actively pump out chemotherapies. Recent data hint that efforts toward GIC characterization and quantification can help predict patient outcomes, and yet the different subpopulations of GICs remain incompletely understood. A better understanding of GIC subtypes and functions proves critical for engineering targeted therapies. Challenges for doing so are discussed, and dopamine receptor antagonists are introduced as new means to enhance the efficacy of the current standard-of-care against GICs.Glioblastoma multiforme (GBM) represents one of the most challenging malignancies due to many factors including invasiveness, heterogeneity, and an immunosuppressive microenvironment. Current treatment modalities have resulted in only modest effect on outcomes. The development of viral vectors for oncolytic immunovirotherapy and targeted drug delivery represents a promising therapeutic prospect for GBM and other brain tumors. A host of genetically engineered viruses, herpes simplex virus, poliovirus, measles, and others, have been described and are at various stages of clinical development. Herein we provide a review of the advances and current state of oncolytic virotherapy for the targeted treatment of GBM and malignant gliomas.Chimeric antigen receptor T (CAR-T) cells, an immunotherapy that demonstrates marked success in treatment of hematologic malignancies, are an emergent therapeutic for patients with glioblastoma (GBM). GBM CAR-T trials have focused on targeting well-characterized antigens in the pathogenesis of GBM. Early stage trials demonstrate initial success in terms of safety and tolerability. There is preliminary evidence of antitumor activity and localization of the CAR-T product to tumoral sites. There are mixed results regarding patient outcomes. Ongoing GBM CAR-T trials will target novel antigens, explore CAR-T combination therapy, design multivalent CAR constructs, and assess the impact of lymphodepletion before CAR-T delivery.The glioblastoma tumor microenvironment is highly immunosuppressed. This immunosuppressive state is engineered by inhibitory molecules secreted by tumor cells that limit activation of immune effector cells, drive T-cell exhaustion, and enhance the immunosuppressive action of tumor-associated myeloid cells. Immunotherapeutic approaches have sought to combat glioblastoma microenvironment immunosuppression with agents such as immune checkpoint inhibitors. Although immune checkpoint blockade in glioblastoma has yielded disappointing results thus far, there is significant interest in the combination of immune checkpoint blockade with other approaches to enhance response.Peptide and dendritic cell vaccines activate the immune system against tumor antigens to combat brain tumors. link3 Vaccines stimulate a systemic immune response by inducing both antitumor T cells as well as humoral immunity through antibody production to cross the blood-brain barrier and combat brain tumors. Recent trials investigating vaccines against peptides (ie, epithelial growth factor receptor variant III, survivin, heat shock proteins, or personalized tumor antigens) and dendritic cells pulsed with known peptides, messenger RNA or unknown tumor lysate targets demonstrate the potential for therapeutic cancer vaccines to become an important therapy for brain tumor treatment.The standard of care treatment for glioblastoma is surgical resection followed by radiotherapy to 60 Gy with concurrent and adjuvant temozolomide with or without tumor-treating fields. Advanced imaging techniques are under evaluation to better guide radiotherapy target volume delineation and allow for dose escalation. Particle therapy, in the form of protons, carbon ions, and boron neutron capture therapy, are being assessed as strategies to improve the radiotherapeutic ratio. Stereotactic, hypofractionated, pulsed-reduced dose-rate, and particle radiotherapy are re-irradiation techniques each uniquely suited for different clinical scenarios. Novel radiotherapy approaches, such as FLASH, represent promising advancements in radiotherapy for glioblastoma.Glioblastoma remains incurable despite advances in surgery, radiation, and chemotherapy, underscoring the need for new therapies. The genetic heterogenicity, presence of redundant molecular pathways, and the blood-brain barrier have limited the applicability of molecularly targeted agents. The therapeutic benefit seen with a small subset of patients suggests, however, that patient selection is critical. Recent investigations show that molecularly targeted synthetic lethality is a promising complementary approach. The article provides an overview of the challenges of molecularly targeted therapy in adults with glioblastoma, including current trials and future therapeutic directions.Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAFKIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune escape, adequacy of tumor penetrance, and sensitivity of brain to treatment-related toxicities.Mismatch repair (MMR) is a highly conserved DNA repair pathway that is critical for the maintenance of genomic integrity. This pathway targets base substitution and insertion-deletion mismatches, which primarily arise from replication errors that escape DNA polymerase proof-reading function. Here, the authors review key concepts in the molecular mechanisms of MMR in response to alkylation damage, approaches to detect MMR status in the clinic, and the clinical relevance of this pathway in glioblastoma multiforme treatment response and resistance.Glioblastomas (GBMs) exhibit altered metabolism to support a variety of bioenergetic and biosynthetic demands for tumor growth, invasion, and drug resistance. Changes in glycolytic flux, oxidative phosphorylation, the pentose phosphate pathway, fatty acid biosynthesis and oxidation, and nucleic acid biosynthesis are observed in GBMs to help drive tumorigenesis. Both the genetic landscape of GBMs and the unique brain tumor microenvironment shape metabolism; therefore, an understanding of how both intrinsic and extrinsic factors modulate metabolism is becoming increasingly important for finding effect targets and therapeutics for GBM.The definition of glioblastomas has continually evolved from a reliance on strict morphologic features to a combination of histologic and molecular criteria, as the understanding of the genetic basis of these tumors expands. Modern pathologic workup of glioblastomas includes intraoperative evaluations with tissue-sparing techniques, histologic assessment with immunohistochemical markers, and comprehensive molecular characterization aiming at personalized targeting of genetic abnormalities. Machine learning analysis of DNA methylation profiles is a breakthrough technology that has bolstered central nervous system tumor classification and discovery and is particularly beneficial for the diagnosis and subtyping of glioblastomas.
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