ABSTRACT
Background: In the past, few patients with primary ciliary dyskinesia (PCD) were diagnosed with the test combination recommended by guidelines (nasal nitric oxide (nNO), genetic testing, and biopsy for electron or video microscopy) [Halbeisen, ERJ, 2019]. In a large international participatory study of people with PCD, we assessed the current situation. Method(s): We used data from COVID-PCD, an international study of people with PCD, who participated between 2020 and 2022. Participants described their diagnostic tests in an online questionnaire, and we used logistic regression to identify explanatory factors. Result(s): 728 participated (median age 27 years, IQR: 12-43;60% female). Among them, 92% reported that any diagnostic testing had been done: 49% nNO, 59% genetics, and 75% biopsy for electron or video microscopy. Most did not know whether the sample had been analysed with TEM or video microscopy. Biopsy was most frequent in all countries except in North America where genetic testing predominated. Only 36% of participants reported all three tests. This proportion was highest in Germany (61%) and lowest in Australia (19%). Recently diagnosed patients reported more tests (nNO OR 1.7, 95%CI 1.1-2.6, genetics OR 4.5, 95%CI 2.9-6.9), and those with situs inversus less (nNO OR 0.5, 95%CI 0.3-0.7, biopsy OR 0.4, 95%CI 0.3-0.7, genetics OR 0.7, 95%CI 0.5-0.97). Conclusion(s): Diagnostic testing in people with PCD differed by country and few reported having undergone all recommended tests. Patients diagnosed long ago should be recalled for supplementary testing to improve diagnostic characterisation as a prerequisite for personalised medicine.
ABSTRACT
Background: Human SARS-CoV-2 infection can induce a wide spectrum of organ dysfunctions, including microvascular impairment [1]. S1 subunit of viral receptor-binding domain binds to the angiotensin-converting enzyme 2 receptor on endothelium and S2 subunit allows the virus to enter endothelial cells. The resulting breakdown of barrier integrity drives a cascade of infammatory and thrombotic events, that aggravate the course of COVID-19 together with other risk factors [2-4]. Up to date, a lower capillary density has been reported in several distinct body districts, using sublingual video microscopy, ocular optical coherence tomography angiography, skin functional laser Doppler perfusion imaging and nailfold videocapillaroscopy (NVC) [5-8]. NVC examination has been performed in adult COVID-19 patients, however, without a control group [8]. Objectives: To confrm the statistical signifcance of the reduction in capillary density per linear millimeter evaluated by NVC in comparison with primary Ray-naud's phenomenon (PRP) patients and control subjects (CNT) and to evaluate the impact of an aggressive therapy against COVID-19 on the sparing in the number of capillaries. Methods: Sixty-one COVID-19 survivors, thirty-one PRP patients and thirty CNT age and sex-matched underwent NVC analysis. Demographic and clinical data of COVID-19 survivors were collected with special regard to concomitant therapies, that included antivirals, antibiotics, anticoagulants and anti-infamma-tory/immunomodulant drugs (glucocorticoids, hydroxychloroquine, IL-6 receptor antagonist). COVID-19 survivors were divided in two subgroups according to the severity of the active infection: thirty-four survivors with past mild-moderate disease (either unneedy for oxygen supplementation or need for Venturi mask) and twenty-seven survivors with past severe disease (need for Continuous Positive Airways Pressure and/or mechanical ventilation). The same Rheumatologist performed NVC evaluations in all patients and controls, using an optical probe, equipped with a 200x magnifcation lens and connected to a picture analysis software (Videocap, DS Medica, Milan, Italy). Absolute capillary number per linear millimeter was counted. Results: COVID-19 survivors underwent NVC examination after a mean period of 126±53 days from the disease onset. Multivariate analysis showed differences in absolute capillary number per linear millimeter (p<0.001) after adjusting for age, sex, body mass index, comorbidities and concomitant drugs. The mean (± standard deviation) absolute nailfold capillary number per linear millimeter was signifcantly lower in severe (8.2±1.15) and mild-moderate (8.4±0.75) COVID-19 survivors than in both PRP (8.7±0.68) and CNT subjects (9.3±0.53) (p<0.001). The analysis of the impact of treatments on capillary density in the severe COVID-19 patients showed a positive trend (preservation of the capillary number) with antivirals (no: 7.8±1.53;yes: 8.5±0.64;p=0.35) and anti-IL-6 receptor antagonist administration (no: 7.8±1.36;yes: 8.6±0.74;p=0.16), while none of the other drugs was shown to be effective (glucocorticoids p = 0.46;antibiotics = 0.52;anticoagulants not evaluable as they were used in all COVID-19 patients). Conclusion: SARS-CoV-2 infection seems associated to a signifcant capillary loss as distinctive NVC feature and data concerning the comparison of capillary density pre COVID-19 and post COVID-19 are desirable to reinforce this observation. The positive trend in saving the number of capillaries induced by aggressive anti-infammatory therapies in COVID-19 survivors needs larger cohorts of patients.
ABSTRACT
The COVID-19 pandemic has forced educational programs, including pathology residency, to move to a physically distanced learning environment. Tandem microscopic review (also known as "double-scoping") of pathology slides is a traditional cornerstone of pathology education. However, this requires the use of a double- or multi-headed optical light microscope which is unfortunately not amenable to physical distancing. The loss of double-scoping has forced educational innovation in order to continue teaching microscopy. Digital pathology options such as whole slide imaging could be considered; however, financial constraints felt by many departments often render this option cost-prohibitive. Alternatively, a shift toward teaching via dynamic virtual microscopy offers a readily available, physically distanced, and cost-conscious alternative for pathology education. Required elements include a standard light microscope, a mounted digital camera, computers, and videoconferencing software to share a slide image with the learner(s). Through survey data, we show immediate benefits include maintaining the essence of the traditional light microscope teaching experience, and additional gains were discovered such as the ability for educators and learners to annotate images in real time, among others. Existing technology may not be initially optimized for a dynamic virtual experience, resulting in lag time with image movement, problems focusing, image quality issues, and a narrower field of view; however, these technological barriers can be overcome through hardware and software optimization. Herein, we share the experience of establishing a dynamic virtual microscopy educational system in response to the COVID-19 pandemic, utilizing readily available technology in the pathology department of a major academic medical center.