High levels of von Willebrand factor with reduced specific activities in hospitalized patients with or without COVID-19.

The COVID-19 pandemic is often accompanied by severe respiratory illness and thrombotic complications. Von Willebrand Factor (VWF) levels are highly elevated in this condition. However, limited data are available on the qualitative activity of VWF in COVID-19. We measured plasma VWF levels quantitatively (VWF antigen) and qualitatively (ristocetin-induced platelet agglutination, glycoprotein IbM (GPIbM) binding, and collagen binding). Consistent with prior reports, VWF antigen levels were significantly elevated in hospitalized patients with or without COVID-19. The GPIbM and collagen binding activity-to-antigen ratios were significantly reduced, consistent with qualitative changes in VWF in COVID-19. Of note, critically ill hospitalized patients without COVID-19 had similar reductions in VWF activity-to-antigen ratios as patients with COVID-19. Our data suggest that qualitative changes in VWF in COVID-19 may not be specific to COVID-19. Future studies are warranted to determine the mechanisms responsible for qualitative changes in VWF in COVID-19 and other critical illnesses.• VWF levels were increased in COVID-19 compared to healthy controls.• VWF activity-to-antigen ratios were decreased in COVID-19 compared to healthy controls.• There were no differences in VWF activity-to-antigen ratios between hospitalized patients with or without COVID-19.• These findings are consistent with qualitative changes in VWF in systemic inflammation which are not specific to COVID-19.• Future studies are needed to define possible roles of changes in conformation or multimer length in the qualitative changes in VWF in systemic inflammation.

Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils, and Mast Cell Degranulation.

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the ß2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.

Chronic Ulcers and Malnutrition in an African Patient.

An 11-year-old girl with a congenitally malformed left hand, sickle cell trait, asthma, and history of appendicitis was transferred from Zambia for evaluation and treatment of widespread suppurative and ulcerative skin lesions that typically appeared after trauma to her skin. The ulcers first presented 3 years earlier but had markedly worsened in the 9 months before transfer, spreading circumferentially on her extremities and abdomen at the site of an appendectomy. They were painful and did not resolve with multiple courses of intravenous antibiotics and close management by a pediatric infectious disease specialist working for a nongovernmental organization (NGO) in her home country. Per NGO records, she had previously been  average weight-for-age. On presentation after international transfer, she was severely malnourished, with lesions covering âˆ¼35% of her body. In initial workup, leukocytosis of 21 × 103 cells per µL (79% neutrophils), hemoglobin of 6.1 g/dL, and mean corpuscular volume of 66 fL were found. Iron studies revealed an iron level of 18 µg/dL, ferritin level of 55 ng/mL, total iron binding capacity of 222 µg/dL, and transferrin saturation of 8%. Inflammatory markers were elevated, C-reactive protein was 20.1 mg/dL, and the erythrocyte sedimentation rate was 131 mm/h. A chest computed tomography scan revealed bilateral pulmonary nodules, the largest in her left upper lobe measuring 2.4 × 2.0 × 1.9 cm. Our panel of experts reviews the evaluation and treatment of this patient with extensive suppurative and ulcerative skin lesions and the factors considered in offering charity care to international patients.

Degos disease: A radiological-pathological correlation of the neuroradiological aspects of the disease.

Malignant atrophic papulosis (Degos disease) is an unusual thrombotic microangiopathy of uncertain etiology. The disease characteristically involves the skin and internal organs, with nervous system involvement more common in children. We present a case with diverse neurological manifestations including cranial nerve palsies, gait instability, and urinary incontinence. The patient also developed white papular lesions on her lower extremities and back. Magnetic resonance imaging (MRI) demonstrated progressive intracranial and spinal abnormalities. Despite treatment with numerous biologic agents, the patient had persistent clinical deterioration and expired one month after admission. We highlight the extensive neurologic manifestations of Degos disease correlated with neuroradiological imaging and pathological features. Nervous system involvement in Degos disease requires careful neurologic and dermatologic exam with central nervous system (CNS) magnetic resonance imaging to distinguish it from non-organic etiologies of similar symptoms.

Microvascular thrombosis: experimental and clinical implications.

A significant amount of clinical and research interest in thrombosis is focused on large vessels (eg, stroke, myocardial infarction, deep venous thrombosis, etc.); however, thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others. Further, microvascular thrombosis has recently been demonstrated in patients with COVID-19, and has been proposed to mediate the pathogenesis of organ injury in this disease. In many of these conditions, microvascular thrombosis is accompanied by inflammation, an association referred to as thromboinflammation. In this review, we discuss endogenous regulatory mechanisms that prevent thrombosis in the microcirculation, experimental approaches to induce microvascular thrombi, and clinical conditions associated with microvascular thrombosis. A greater understanding of the links between inflammation and thrombosis in the microcirculation is anticipated to provide optimal therapeutic targets for patients with diseases accompanied by microvascular thrombosis.

Intra-individual assessment of speech and music perception in cochlear implant users with contralateral Cochlear™ and MED-EL™ systems.

CONCLUSION: Whilst objective testing on music perception showed no individual differences between cochlear implant (CI) devices, subjective music perception was found to be superior with the MED-EL device in the majority of cases evaluated. OBJECTIVE: To compare speech and music perception through two different CI systems in the same individuals. METHODS: Six post-lingually deaf patients, who had been implanted with a Cochlear™ Nucleus(®) device in one ear and a MED-EL SONATATI(100) on the contralateral side were evaluated. One subject was excluded from group analysis because of significant differences in performance between ears. Subjects completed a questionnaire designed to assess implant users' listening habits. Subjective assessments of each subject were made for comparison of speech and music perception with each system and preferences of system. The subjects consecutively used each system with the contralateral device turned off, and were objectively assessed for specific musical skills. Speech perception in quiet and in noise was tested. RESULTS: For all objective tests of music discrimination and speech perception in noise, there were no statistically significant differences between MED-EL and Cochlear CI systems. Subjectively, four subjects thought their MED-EL device was better than their Cochlear device for music appreciation. Four thought that music sounded more natural, less tinny and more reverberant with their MED-EL CI than with their Cochlear CI. One subject rated all these to be equal.

Bilateral sequential cochlear implantation in the congenitally deaf child: evidence to support the concept of a 'critical age' after which the second ear is less likely to provide an adequate level of speech perception on its own.

This study attempts to answer the question of whether there is a 'critical age' after which a second contralateral cochlear implant is less likely to provide enough speech perception to be of practical use. The study was not designed to predict factors that determine successful binaural implant use, but to see if there was evidence to help determine the latest age at which the second ear can usefully be implanted, should the first side fail and become unusable.Outcome data, in the form of speech perception test results, were collected from 11 cochlear implant programmes in the UK and one centre in Australia. Forty-seven congenitally bilaterally deaf subjects who received bilateral sequential implants were recruited to the study. The study also included four subjects with congenital unilateral profound deafness who had lost all hearing in their only hearing ear and received a cochlear implant in their unilaterally congenitally deaf ear. Of those 34 subjects for whom complete sets of data were available, the majority (72%) of those receiving their second (or unilateral) implant up to the age of 13 years scored 60 per cent or above in the Bamford Kowal Bench (BKB) sentence test, or equivalent. In contrast, of those nine receiving their second or unilateral implant at the age of 15 or above, none achieved adequate levels of speech perception on formal testing: two scored 29 per cent and 30 per cent, respectively, and the rest seven per cent or less.A discriminant function analysis performed on the data suggests that it is unlikely that a second contralateral implant received after the age of 16 to 18 years will, on its own, provide adequate levels of speech perception. As more children receive sequential bilateral cochlear implants and the pool of data enlarges the situation is likely to become clearer.The results provide support for the concept of a 'critical age' for implanting the second ear in successful congenitally deaf unilateral cochlear implant users. This would argue against 'preserving' the second ear beyond a certain age, in order to use newer models of cochlear implant or for the purpose of hair cell regeneration and similar procedures in the future. The results suggest a new and more absolute reason for bilateral implantation of congenitally deaf children at an early age.

The association of codeine, macrocytosis and bilateral sudden or rapidly progressive profound sensorineural deafness.

CONCLUSIONS: Codeine shows a similar association with profound deafness to other opiates. Good cochlear implant outcomes suggest a sensory disorder. Although macrocytosis could be due to confounding factors, the lack of other consistent findings may signify a vascular pathology. OBJECTIVES: To describe a series of patients identified as codeine users after referral for cochlear implantation. PATIENTS AND METHODS: This was a retrospective case series review. Patients were identified by the senior audiologist. Information regarding mode of onset of deafness, past medical history, drug and alcohol history, investigations and audiological outcomes following cochlear implantation was collected from hospital records and patient questionnaires. RESULTS: Ten patients were included in the study. All patients had taken codeine phosphate and paracetamol in combination for several years, usually at greater than recommended daily dose. All patients presented with sudden or rapidly progressive bilateral deafness. All patients had a significant macrocytosis at the time of deafness (mean cell volume (MCV): mean 115 fL; range 105-132 fL). No other investigation was consistently abnormal. Four patients had a history of alcoholism. Seven patients had abnormal liver function tests. Patients usually performed well with cochlear implants (CUNY sentence scores without lip reading >90% in 9 of 10 patients).