Association of timing of congenital diaphragmatic hernia repair with survival and morbidity for patients not requiring extra-corporeal life support.

BACKGROUND: While physiologic stabilization followed by repair has become the accepted paradigm for management of congenital diaphragmatic hernia (CDH), few studies have examined the effect of incremental changes in operative timing on patient outcomes. We hypothesized that later repair would be associated with higher morbidity and mortality. METHODS: Data were queried from the CDH Study Group (CDHSG) from 2007-2020. Patients with chromosomal or cardiac abnormalities and those who were never repaired or required pre-repair extra-corporeal life support (ECLS) were excluded. Time to repair was analyzed both as a continuous variable and by splitting the cohort into top/bottom percentiles. The primary outcome of interest was in-hospital mortality. Secondary outcomes included need for and duration of post-repair ventilatory and nutritional support. RESULTS: A total of 4,104 CDH infants were included. Median time to repair was 4 days (IQR 2-6). On multivariable analysis, high-risk (CDHSG stage C/D) defects and lower birthweight predicted later repair. Overall, in-hospital mortality was 6%. On univariate analysis, there was no difference in the number of days to repair between survivors and non-survivors. On risk-adjusted analysis, single-day changes in day of repair were not associated with increased mortality. Later repair was associated with longer time to reach full oral feeds, increased post-repair ventilator days, and increased need for tube feeds and supplementary oxygen at discharge. CONCLUSIONS: For infants with isolated CDH not requiring pre-operative ECLS, there is no difference in mortality based on timing of repair, but single-day delays in repair are associated with increased post-repair duration of ventilatory and nutritional support.

Understanding the age divide in COVID-19: why are children overwhelmingly spared?

The rapid emergence and subsequent global dissemination of SARS-CoV-2 disease (COVID-19) has resulted in over 4 million cases worldwide. The disease has a marked predilection for adults, and children are relatively spared. Understanding the age-based differences in pathophysiological pathways and processes relevant to the onset and progression of disease both in the clinical course and in experimental disease models may hold the key to the identification of therapeutic targets. The differences in the clinical course are highlighted by the lack of progression of the SARS-CoV-2 infection beyond mild symptoms in a majority of children, whereas in adults the disease progresses to acute lung injury and an acute respiratory distress syndrome (ARDS)-like phenotype with high mortality. The pathophysiological mechanisms leading to decreased lung injury in children may involve the decreased expression of the mediators necessary for viral entry into the respiratory epithelium and differences in the immune system responses in children. Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry. The immune system differences may include a relative preponderance of CD4+ T cells, decreased neutrophil infiltration, decreased production of proinflammatory cytokines, and increased production of immunomodulatory cytokines in children compared with adults. Notably, the developing lung in children may have a greater capacity to recover and repair after viral infection. Understanding the relative contributions of the above processes to the protective phenotype in the developing lung can guide the trial of the appropriate therapies in adults.

Prenatally diagnosed congenital diaphragmatic hernia: optimal mode of delivery?

OBJECTIVE: To evaluate if the delivery mode of infants with prenatally diagnosed congenital diaphragmatic hernia (CDH) affects the outcome. STUDY DESIGN: Data from the CDH Study Group database of infants with prenatal diagnosis between 2001-2015 were divided into four delivery mode groups: vaginal spontaneous, vaginal induced, elective caesarean section, and emergent caesarean section. Outcomes were analyzed in relation to the time of day of delivery and the gestational age at birth. RESULTS: A total of 3906 cases of prenatally diagnosed CDH were assessed, with an overall survival of 64%. There were no differences in patient characteristics, requirement for extracorporeal membrane oxygenation, length of hospital stay or intubation, requirement for O2 at 30 days or overall survival. The time of day at birth did not affect the outcome. There was no difference in outcome between the different delivery modes at similar gestational age (GA) at birth, with worse outcomes at lower GA. CONCLUSIONS: Neither the mode nor time of delivery seems to affect the overall outcome for patients with prenatally diagnosed CDH. Outcome is strongly associated with the GA at birth.

Medical photography: current technology, evolving issues and legal perspectives.

Medical photographic image capture and data management has undergone a rapid and compelling change in complexity over the last 20 years. This is because of multiple factors, including significant advances in ease of photograph capture, alongside an evolution of mechanisms of data portability/dissemination, combined with governmental focus on health information privacy. Literature to guide medical, legal, governmental and business professionals when dealing with issues related to medical photography is virtually nonexistent. Herein, we will address the breadth of uses of medical photography, device properties/specific devices utilised for image capture, methods of data transfer and dissemination and patient perceptions and attitudes regarding photography in a medical setting. In addition, we will address the legal implications, including legal precedent, copyright and privacy law, informed consent, protected health information and the Health Insurance Portability and Accountability Act (HIPAA), as they pertain to medical photography.

Current trends in cell therapy for pediatric acquired brain injury.

Pediatric traumatic brain injury (TBI) represents a major burden on healthcare worldwide. In the United States, TBI accounts for 435000 Emergency Department visits, 37000 hospital admissions, and approximately 2500 deaths each year. While aggressive early rehabilitation has shown some functional improvement, the acute care of TBI with focus on controlling intracranial pressure while maintaining adequate cerebral perfusion has not shown the ability to reverse neuronal injury on either a cellular or subcellular level. Preliminary investigation into the use of cell therapeutics has shown promise for the treatment of TBI in animal models. While progenitor cells may potentially act via altering the intracerebral milieu (modulation of inflammatory response and trophic factor secretion), the exact mechanism remains controversial. In addition, traditional delivery vehicles (intravenous, intra-arterial, intrathecal injections, and direct implantation) have shown significant barriers to translation coupled with inconsistent results. Therefore, investigation into novel delivery vehicles such as nanofiber scaffolds and hydrogels could enhance transplant cell viability, engraftment, and efficacy. Overall, a large amount of preclinical work remains to clearly define optimal progenitor cell type, dosage, and delivery vehicle. The optimal therapeutic benefit may be seen using a combination of therapies (controlled hypothermia, hypertonic therapy, and/or cellular therapeutics) to attack the complex pathophysiology of TBI at multiple points.

An octakis-intercalating molecule.

Herein we report the synthesis and characterization of a polyintercalator with eight potential intercalating l,4,5,8-naphthalenetetracarboxylic diimide (NDI) units linked in a head-to-tail arrangement via a peptide linker. UV spectroscopy and viscometry measurements indicated the molecule binds to double-stranded DNA with all eight NDI units intercalated simultaneously. Competition dialysis and DNAse 1 footprinting studies revealed a preference for GC-rich regions of DNA, and circular dichroism studies revealed significant distortion of B-form DNA upon binding. Our so-called "octamer" represents, to the best of our knowledge, the first intercalator that binds as an octakis-intercalator, capable of spanning at least 16 base pairs of DNA.

Altered sequence specificity identified from a library of DNA-binding small molecules.

BACKGROUND: The ability to target specific DNA sequences using small molecules has major implications for basic research and medicine. Previous studies revealed that a bis-intercalating molecule containing two 1,4,5,8-napthalenetetracarboxylic diimides separated by a lysine-tris-glycine linker binds to DNA cooperatively, in pairs, with a preference for G + C-rich sequences. Here we investigate the binding properties of a library of bis-intercalating molecules that have partially randomized peptide linkers. RESULTS: A library of bis-intercalating derivatives with varied peptide linkers was screened for sequence specificity using DNase I footprinting on a 231 base pair (bp) restriction fragment. The library mixtures produced footprints that were generally similar to the parent bis-intercalator, which bound within a 15 bp G + C-rich repeat above 125 nM. Nevertheless, subtle differences in cleavage enhancement bands followed by library deconvolution revealed a derivative with novel specificity. A lysine-tris-beta-alanine derivative was found to bind preferentially within a 19 bp palindrome, without substantial loss of affinity. CONCLUSIONS: Synthetically simple changes in the bis-intercalating compounds can produce derivatives with novel sequence specificity. The large size and symmetrical nature of the preferred binding sites suggest that cooperativity may be retained despite modified sequence specificity. Such findings, combined with structural data, could be used to develop versatile DNA ligands of modest molecular weight that target relatively long DNA sequences in a selective manner.