Impact of P-selectin-PSGL-1 Axis on Platelet-Endothelium-Leukocyte Interactions in Fatal COVID-19.

In critically ill patients infected with SARS-CoV-2, early leukocyte recruitment to the respiratory system was found to be orchestrated by leukocyte trafficking molecules accompanied by massive secretion of proinflammatory cytokines and hypercoagulability. Our study aimed to explore the interplay between leukocyte activation and pulmonary endothelium in different disease stages of fatal COVID-19. Our study comprised 10 COVID-19 postmortem lung specimens and 20 control lung samples (5 acute respiratory distress syndrome, 2 viral pneumonia, 3 bacterial pneumonia, and 10 normal), which were stained for antigens representing the different steps of leukocyte migration: E-selectin, P-selectin, PSGL-1, ICAM1, VCAM1, and CD11b. Image analysis software QuPath was used for quantification of positive leukocytes (PSGL-1 and CD11b) and endothelium (E-selectin, P-selectin, ICAM1, VCAM1). Expression of IL-6 and IL-1ß was quantified by RT-qPCR. Expression of P-selectin and PSGL-1 was strongly increased in the COVID-19 cohort compared with all control groups (COVID-19:Controls, 17:23, P < .0001; COVID-19:Controls, 2:75, P < .0001, respectively). Importantly, P-selectin was found in endothelial cells and associated with aggregates of activated platelets adherent to the endothelial surface in COVID-19 cases. In addition, PSGL-1 staining disclosed positive perivascular leukocyte cuffs, reflecting capillaritis. Moreover, CD11b showed a strongly increased positivity in COVID-19 compared with all controls (COVID-19:Controls, 2:89; P = .0002), indicating a proinflammatory immune microenvironment. Of note, CD11b exhibited distinct staining patterns at different stages of COVID-19 disease. Only in cases with very short disease course, high levels of IL-1ß and IL-6 mRNA were observed in lung tissue. The striking upregulation of PSGL-1 and P-selectin reflects the activation of this receptor-ligand pair in COVID-19, increasing the efficiency of initial leukocyte recruitment, thus promoting tissue damage and immunothrombosis. Our results show that endothelial activation and unbalanced leukocyte migration play a central role in COVID-19 involving the P-selectin-PSGL-1 axis.

Autochthonous Crimean-Congo Hemorrhagic Fever in Spain.

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, viral, tickborne disease. In Europe, cases have been reported only in the southeastern part of the continent. We report two autochthonous cases in Spain. The index patient acquired the disease through a tick bite in the province of Ávila - 300 km away from the province of Cáceres, where viral RNA from ticks was amplified in 2010. The second patient was a nurse who became infected while caring for the index patient. Both were infected with the African 3 lineage of this virus. (Funded by Red de Investigación Cooperativa en Enfermedades Tropicales [RICET] and Efficient Response to Highly Dangerous and Emerging Pathogens at EU [European Union] Level [EMERGE].).

[Rare differential diagnosis of an osteolytic lesion of the mandible in a young adult]. / Seltene Differenzialdiagnose bei osteolytischer Läsion des Unterkiefers einer jungen Erwachsenen.

We report a rarely occurring hematologic neoplasm in a young adult. Hematologic neoplasms were first described in 2008 and are now included in both accepted tumor classification systems, i.e., International Consensus Classification and World Health Organization. This hematologic neoplasm shows a characteristic ALK positivity in immunohistochemical examination and correspondingly, ALK fusion genes in the molecular analysis. Pathologists should be aware of this entity, particularly as it is challenging to differentiate from other more frequent neoplasms of the same disease group or mesenchymal neoplasm with ALK aberration.

Case report: Solitary mass of the sciatic nerve confirmed as a primary extranodal manifestation of diffuse large B-cell lymphoma in a geriatric patient.

Background: Neoplastic lesions affecting peripheral nerves are rare in the general population and, most often, are benign peripheral nerve sheath tumors. However, a minority of lesions represent high-grade malignancies associated with a poor prognosis, such as malignant peripheral nerve sheath tumors (MPNSTs). Very rarely, these tumors represent peripheral non-nerve sheath tumors (PNNSTs), such as hematological neoplasms that impair nerve function. These can be hard to distinguish from MPNSTs and other lesions arising from the nerve itself. In the present case report, we describe a rare case of direct infiltration of nerves by tumor cells of a hematological neoplasm. Methods: We report the case of a 90-year-old woman with acute onset of right-sided foot palsy, sensory loss, and pain, caused by an extensive solitary mass of the sciatic nerve in the thigh. We present and discuss the clinical presentation, multimodal diagnostic procedures, and treatment. Results: MRI of the right thigh and the caudal pelvis revealed a contrast-enhancing lesion infiltrating the sciatic nerve. Additionally performed staging imaging was non-revealing. After multidisciplinary discussion in the neuro-oncology tumor board, a MPNST was suspected and the patient underwent radical tumor resection. However, final histopathology revealed a diffuse large B-cell lymphoma (DLBCL). The patient received adjuvant palliative local radiotherapy which led to acceptable symptom control. Conclusion: Rare PNNSTs, including extranodal manifestations of DLBCL can have similar clinical and radiological diagnostical features as PNSTs. Comprehensive diagnostic workup of contrast-enhancing lesions affecting peripheral nerves including MRI and metabolic imaging are recommended. Discussion in interdisciplinary tumor boards facilitates finding individual treatment approaches.

Left Ventricular Physiology and Ventricular-Vascular Interactions in Young Patients After Heart Transplantation.

Background In patients after heart transplantation, systemic arterial hypertension and enhanced central aortic stiffness contribute to increased ventricular afterload, which might lead to graft dysfunction. The aim of our study was to characterize systemic arterial elastance and its impact on left ventricular function and ventriculo-arterial coupling in a cohort of children, adolescents, and young adults after heart transplantation using invasive conductance catheter technique. Methods and Results Thirty patients who had heart transplants (age, 20.0±6.5 years, 7 female) underwent invasive cardiac catheterization including pressure-volume loop analysis. Load-independent parameters of systolic (ventricular elastance [Ees]) and diastolic (ventricular compliance) function as well as systemic arterial elastance (Ea, end-systolic pressure/stroke volume) and ventriculo-arterial coupling (Ea/Ees) were assessed at baseline level and during dobutamine infusion (10 µg/kg/min). Ees showed an appropriate increase under inotropic stimulation from 0.43 (0.11-2.52) to 1.00 (0.20-5.10) mm Hg/mL/m2 (P<0.0001), whereas ventricular compliance remained rather unchanged (0.16±0.10 mm Hg/mL/m2 to 0.12±0.07 mm Hg/mL/m2; P=0.10). Ventriculo-arterial coupling Ea/Ees was abnormal at rest and did not improve significantly under dobutamine (1.7 [0.6-6.7] to 1.3 [0.5-4.9], P=0.70) due to a simultaneous rise in Ea from 0.71 (0.37-2.82) to 1.10 (0.52-4.03) mm Hg/mL/m2 (P<0.0001). Both Ees and ventricular compliance were significantly associated with Ea at baseline and under dobutamine infusion. Conclusions Patients who underwent heart transplantation show impaired ventriculo-arterial coupling at rest and under inotropic stimulation despite preserved left ventricular contractile reserve. An abnormal response in vascular function resulting in increased afterload seems to represent an important factor that may play a role for the development of late graft failure.

Clinical Management of Squamous Cell Carcinoma of the Conjunctiva.

BACKGROUND Conjunctival squamous cell carcinoma is the most common non-pigmented malignancy of the ocular surface. This report illustrates the clinical management of squamous cell carcinoma of the conjunctiva. CASE REPORT A 33-year-old female was referred to our eye hospital with a tumorous lesion on the nasal bulbar conjunctiva of the right eye. A topical therapy with antibiotic and corticosteroid eye drops did not change the lesion. The conjunctival tumor was widely resected. The histopathological diagnosis suggested a squamous cell carcinoma. After resection, a treatment with topical mitomycin C (MMC) 0.02% eye drops were started 4 times daily for 14 days. Two cycles of treatment were done with a 2-week interval during which only artificial tears eye drops were administered. At the 12-month follow-up, there was no sign of recurrence. CONCLUSIONS This case illustrates the effective and successful clinical management of squamous cell carcinoma of the conjunctiva with excision and postoperative treatment with MMC 0.02% eye drops.