Transplantation of a genetically modified porcine heart into a live human.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.

Genetically engineered pig heart transplantation in non-human primates.

Background: Improvement in gene modifications of donor pigs has led to the prevention of early cardiac xenograft rejection and significantly prolonged cardiac xenograft survival in both heterotopic and orthotopic preclinical non-human primate (NHP) models. This progress formed the basis for FDA approval for compassionate use transplants in two patients.

Methods: Based on our earlier report of 9-month survival of seven gene-edited (7-GE) hearts transplanted (life-supporting orthotopic) in baboons, we transplanted 10 gene-edited pig hearts into baboons (n = 4) using non-ischemic continuous perfusion preservation (NICP) and immunosuppression regimen based on co-stimulation blockade by anti-CD40 monoclonal antibody.

Venoarterial Extracorporeal Membrane Oxygenation Therapy in Patients with Sickle Cell Disease: Case Series and Review for Intensive Care Physicians.

Sickle cell disease (SCD) is associated with substantial morbidity and early mortality in afflicted adults. Cardiopulmonary complications that occur at increased frequency in SCD such as pulmonary embolism, pulmonary arterial hypertension, and acute chest syndrome can acutely worsen right ventricular function and lead to cardiogenic shock. Mechanical circulatory support including venoarterial extracorporeal membrane oxygenation (VA ECMO) is being increasingly utilized to treat hemodynamic collapse in various patient populations.

Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report.

Background: A genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ineligible for an allograft. This report details our current understanding of factors important to the xenotransplantation outcome.

Methods: Physiological and biochemical parameters critical for the care of all heart transplant recipients were collected in extensive clinical monitoring in an intensive care unit.

Dataset for the reporting of neoplasms of the heart, pericardium, and great vessels: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) was founded by major pathology organizations from around the world to produce internationally standardized and evidence-based datasets for pathologists' reporting of cancer. Its goal is to improve cancer patient outcomes worldwide and to advance international benchmarking in cancer management. The ICCR cancer dataset development schedule is aligned with revisions of the WHO Classification of Tumours ("Blue Book") series, and in 2015 ICCR developed an initial series of thoracic datasets including a dataset for neoplasms of the heart, pericardium, and great vessels.

The Reemergence of Measles.

Objectives: Present-day pathologists may be unfamiliar with the histopathologic features of measles, which is a reemerging disease. Awareness of these features may enable early diagnosis of measles in unsuspected cases, including those with an atypical presentation. Using archived tissue samples from historic patients, a unique source of histopathologic information about measles and other reemerging infectious diseases, we performed a comprehensive analysis of the histopathologic features of measles seen in commonly infected tissues during prodrome, active, and late phases of the disease.

Iatrogenic thrombosis of the deep inferior epigastric artery during diagnostic angiography-a rare complicating factor during rectus free flap harvest.

We describe a 28-year-old man who sustained an open IIIB left ankle fracture dislocation with heel pad avulsion. The patient underwent formal angiography of the left lower extremity, followed by free tissue transfer of a rectus abdominis flap several days later. Intraoperatively, a thrombus was identified in the deep inferior epigastric artery above the femoral artery access site requiring thrombectomy.

Nivolumab-induced peritonitis with peritoneal mesothelial hyperplasia mimicking metastatic mesothelioma.

A 57-year-old man developed a mesothelial proliferation in the peritoneum, several months after he was diagnosed with biopsy-proven epithelioid mesothelioma of the pleura and having undergone several treatments with checkpoint inhibitor immunotherapy. The differential diagnosis was metastatic mesothelioma from the lung primary, versus a reactive process. A diagnosis of atypical mesothelial proliferation was made.

Ischemia reperfusion injury facilitates lung allograft acceptance through IL-33-mediated activation of donor-derived IL-5 producing group 2 innate lymphoid cells.

Pathways regulating lung alloimmune responses differ from most other solid organs and remain poorly explored. Based on our recent work identifying the unique role of eosinophils in downregulating lung alloimmunity, we sought to define pathways contributing to eosinophil migration and homeostasis. Using a murine lung transplant model, we have uncovered that immunosuppression increases eosinophil infiltration into the allograft in an IL-5-dependent manner.

Sarcomatoid Mesothelioma with Bland Histologic Features: A Potential Pitfall in Diagnosis.

Sarcomatoid mesotheliomas can be challenging to diagnose on small biopsy specimens, where limited material may preclude definitive assessment of invasion and lesional cells can have relatively bland cytology with no mesothelial marker expression. We report a case of a patient who presented with a pleural effusion and had subsequent pleural biopsy that showed a bland, uniform spindle cell proliferation in a mildly myxoid background. There was little if any collagen; no chest wall, soft tissue, or fat; and mesothelial markers were negative.

Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19.

Importance: Loss of smell is an early and common presentation of COVID-19 infection. Although it has been speculated that viral infection of olfactory neurons may be the culprit, it is unclear whether viral infection causes injuries in the olfactory bulb region.

Objective: To characterize the olfactory pathology associated with COVID-19 infection in a postmortem study.

Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months.

We report orthotopic (life-supporting) survival of genetically engineered porcine cardiac xenografts (with six gene modifications) for almost 9 months in baboon recipients. This work builds on our previously reported heterotopic cardiac xenograft (three gene modifications) survival up to 945 days with an anti-CD40 monoclonal antibody-based immunosuppression. In this current study, life-supporting xenografts containing multiple human complement regulatory, thromboregulatory, and anti-inflammatory proteins, in addition to growth hormone receptor knockout (KO) and carbohydrate antigen KOs, were transplanted in the baboons.

An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need.

Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity.

Unlabelled: Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic especially for low- and middle-income countries. While vaccines against SARS-CoV-2 based on mRNA and adenoviral-vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are needed to meet global demand. In this context, protein subunit vaccines formulated with appropriate adjuvants represent a promising approach to address this urgent need.

Ischemic Heart Disease: Noninvasive Imaging Techniques and Findings.

Ischemic heart disease is a leading cause of death worldwide and comprises a large proportion of annual health care expenditure. Management of ischemic heart disease is now best guided by the physiologic significance of coronary artery stenosis. Invasive coronary angiography is the standard for diagnosing coronary artery stenosis.

A comprehensive assessment of environmental exposures and the medical history guides multidisciplinary discussion in interstitial lung disease.

Background: Multidisciplinary discussion (MDD) is widely recommended for patients with interstitial lung disease (ILD), but published primary data from MDD has been scarce, and factors influencing MDD other than chest computed tomography (CT) and lung histopathology interpretations have not been well-described.

Methods: Single institution MDD of 179 patients with ILD.

Results: MDD consensus clinical diagnoses included autoimmune-related ILD, chronic hypersensitivity pneumonitis, smoking-related ILD, idiopathic pulmonary fibrosis, medication-induced ILD, occupation-related ILD, unclassifiable ILD, and a few less common pulmonary disorders.

Intimal Sarcoma of the Great Vessels.

Intimal sarcomas of the pulmonary artery and aorta are rare entities with a poor prognosis. In many instances, pulmonary artery sarcomas are misinterpreted as acute or chronic pulmonary thromboembolism, whereas aortic intimal sarcomas are often misdiagnosed as protuberant atherosclerotic disease or intimal thrombus. Discernment of intimal sarcomas from these and other common benign entities is essential for the timely initiation of aggressive therapy.

A Cardiac Amyloidosis Presentation: Atrial Mass Versus Thrombus.

Cardiac neoplasms are a rare finding of which a cardiac myxoma is the most commonly encountered. Therefore, a density identified in the left atrium commonly leads to the presumptive diagnosis of an atrial myxoma. However, other pathologies, such as atrial thrombi, can mimic in clinical presentation and appearance to a myxoma.

DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score.

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group.

Pod Dehiscence in Hairy Vetch ( Roth).

Hairy vetch, (Roth), is a cover crop that does not exhibit a typical domestication syndrome. Pod dehiscence reduces seed yield and creates weed problems for subsequent crops. Breeding efforts aim to reduce pod dehiscence in hairy vetch.

Recutting Blocks of Prostate Needle Biopsies: How Much Diagnostic Yield Is Gained?

. The criteria for "active surveillance" depend in part on quantification of tumor extent and grade on prostate biopsies. It is known that false-negative biopsies may occur from incomplete sectioning of cores within the paraffin blocks.

Brown Bowel Syndrome: A Multi-institutional Case Series.

Brown bowel syndrome (BBS) is a rare condition associated with vitamin E deficiency and defined by prominent lipofuscin deposition in the muscularis propria. Eight unique cases of BBS were identified: 5 men and 3 women (mean age=58.6 y).