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Summary: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy. Methods: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course. Findings: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41–78). Median disease course (time from onset of symptoms to death) was 22 days (range 5–44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5–44]; ten patients with neutrophilic plugs, 21 days [5–44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.. Interpretation: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19. Funding: Amsterdam UMC Corona Research Fund.

Item does not contain fulltext INTRODUCTION: Intestinal vaginoplasty with a sigmoid colon or ileal segment is an established surgical technique for vaginal reconstruction. Little has been reported on long-term (functional) outcome and postoperative quality of life. AIMS: To assess the surgical and long-term psychological outcomes of secondary intestinal vaginoplasty performed from 1970 through 2000 in transgender women. METHODS: Transgender women who underwent intestinal vaginoplasty from 1970 through 2000 were identified from our hospital registry. Demographics, surgical characteristics, complications, and reoperations were recorded. Traceable women were invited to fill out a set of questionnaires (quality-of-life questionnaire, Female Sexual Function Index, Amsterdam Hyperactive Pelvic Floor Scale for Women, Female Genital Self-Imaging Scale, and self-evaluation of vaginoplasty questionnaire) and attend the outpatient clinic for physical, endoscopic, and histologic examination of the neovagina. MAIN OUTCOME MEASURES: Primary outcomes were complications, reoperations, self-perceived quality of life, and functional and esthetic self-evaluation. RESULTS: Twenty-four transgender women were identified who underwent intestinal vaginoplasty as a secondary procedure from 1970 through 2000. There were no intraoperative complications. Three intestinal neovaginas were surgically removed because of postoperative complications. Nineteen women (79%) underwent at least one genital reoperation, most commonly introitus plasty (n = 13, 54%). Five women were deceased at time of analysis. Nine women consented to partake in the study (median age = 58 years, range = 50-73; median postoperative time = 29.6 years, range = 17.2-34.3). They were generally satisfied with life and scored 5.9 of 7 on a subjective happiness scale. Neovaginal functionality was rated as 7.3 and appearance as 7.4 of 10. CONCLUSION: In our institution, intestinal vaginoplasty before 2000 was always performed as a revision procedure after a previous vaginoplasty had failed. Although surgical corrections were frequently necessary, women reported satisfaction with the surgical outcome and with life in general.

Coeliac disease (CD) is the most common cause of villous atrophy and is increasingly recognized. The majority of CD patients responds to a gluten-free diet (GFD). However, some patients experience persistence or recurrence of symptoms despite a GFD. These patients require further diagnostic workup. We describe a 62-year-old female with recurring symptoms attributed to refractory coeliac disease (RCD) type I. A 66-year-old patient with a similar history had aberrant intraepithelial lymphocytes characteristic for RCD type II in her duodenum. Furthermore, in a third CD patient described here, microscopic colitis was responsible for diarrhoea that persisted despite strict dietary adherence. Microscopic colitis is strongly associated with CD and should be considered in patients with this disease. On the basis of these three illustrative case studies, we discuss the causes of non-responsive CD and their respective diagnostic workup.