Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient

Patients who are immunosuppressed, such as solid organ transplant recipients (SOTRs), are known to have a higher risk of developing cutaneous squamous cell carcinoma (cSCC). This population is at a higher risk of metastasis and worse disease-specific survival, with over 1 million cases and an estimated 3,932 to 8,791 deaths each year in the United States. Large cancer genomic databases have reported on genomic drivers for many cancer subtypes, yet cSCC has not been included. The immunosuppressed population is generally ineligible to receive immunotherapy which poses a challenge for treatment options in cases that develop metastasis. After we performed a PRISMA-compliant systematic review of metastatic cSCC cases in immunosuppressed patients, we found there to be a lack of systematic reporting in the literature revealing gaps in the characterization of metastatic cSCC specifically for this population. We hypothesized that a UNMC cohort of metastatic cSCC cases in immunosuppressed individuals will show worse rates of disease-specific death compared to immunocompetent matched controls and that these differences may correlate with different genetic drivers of disease. A review of immunosuppressed patients with a diagnosis of cSCC seen at UNMC was conducted from 2010-2020. These patients were case matched with 3 other cohorts: immunosuppressed patients with a localized cSCC, immunocompetent patients with a confirmed lymph node metastasis, and immunocompetent patients with a localized cSCC. The majority of tumors for both immunosuppressed and immunocompetent metastatic cohorts were staged T3. These populations were also found to have the lowest probability of survival. A 40% decline in probability of survival from metastatic immunocompetent patients to immunosuppressed patients suggests that immunosuppression is an important risk factor in determining disease specific death. We preformed whole exome sequencing on 26 samples of FFPE tissue from our previously created cohort to identify alterations that may be associated with oncogenesis in this patient population. Using this data, we found high UV exposure signatures consistent with previously published data and signatures of unknown etiology that may indicate new areas to study for tumor progression in cSCC patients. Possible cancer driver genes and genes regulating the tumor microenvironment were discovered. We also found a higher fraction of samples in the immunosuppressed metastatic cSCC cohort with mutated genes in the PI3K pathway, leading us to believe PI3K/mTOR inhibitors could be used as a possible treatment option. Clinical characteristics seen in our UNMC cohort and data from whole exome sequencing study could help increase treatment options and improve the prognosis of these individuals

Unconventional 2:1 Ventricular Pacing in a Neonate with Congenital Heart Block and Biventricular Noncompaction

Congenital complete heart block with concomitant biventricular noncompaction cardiomyopathy has been reported once previously. Although not universal, when restrictive physiology is present, impaired diastolic filling may pose a distinct challenge to pacing during the neonatal period. We present the case of a neonate with congenital complete heart block and biventricular noncompaction that resulted in severe diastolic dysfunction and atrioventricular dyssynchrony. We intentionally used 2:1 ventricular pacing to provide atrioventricular synchrony with every paced beat, and this resulted in hemodynamic and clinical improvement. This unconventional pacing technique may be beneficial in other neonates who have complete heart block and diastolic dysfunction

Developed in collaboration with and endorsed by the Heart Rhythm Society (HRS), the American College of Cardiology (ACC), the American Heart Association (AHA), and the Association for European Paediatric and Congenital Cardiology (AEPC). Endorsed by the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS).

AbstractIn view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients

Supplemental Appendix for "Metastatic squamous cell carcinoma is associated with a lower disease-specific survival in immunosuppressed patients: a matched case-control study "

Supplemental Appendix for "Metastatic squamous cell carcinoma is associated with a lower disease-specific survival in immunosuppressed patients: a matched case-control study &quot

Supplemental Appendix for "Metastatic squamous cell carcinoma is associated with a lower disease-specific survival in immunosuppressed patients: a matched case-control study "

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