No abstract

Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected. ll

Colorectal cancer is not one disease but rather a collection of neoplastic diseases. Due to heterogeneity in the disease biology, therapy response, and prognosis, extensive disease stratification is required. Therefore, TNM stage, microsatellite status, tumor grade, lymphovascular invasion, and other parameters are assessed in the pathology report to indicate the extent and prognosis of the disease. The mutation status of KRAS, BRAF, and NRAS is also investigated in a metastatic context to predict the response to anti-EGFR therapy. Recently, 4 distinct molecular subtypes of colorectal cancer have been described that have both prognostic and therapeutic relevance. In addition, characterization of the inflammatory infiltrate revealed major differences in the amount and location of inflammatory cells in distinct colorectal tumor types. Together, all of these parameters help to stratify patients into different therapeutic and prognostic subgroups. However, this stratification is not unambiguous since tumors often display intratumoral heterogeneity, whereby several subpopulations within one tumor show differences in morphology, inflammatory infiltrate, mutational status, or gene expression profile. This article gives an overview of all of the current known data with regard to tumor heterogeneity at both inter- and intratumoral levels.

No abstract

Lung transplantation from a donor previously infected with SARS-CoV-2

No abstract

BackgroundLong-term survival after lung transplantation (LTx) is hampered by development of chronic lung allograft dysfunction (CLAD). Pseudomonas aeruginosa (PA) is an established risk factor for CLAD. Therefore, we investigated the effect of PA eradication on CLAD-free and graft survival.MethodsPatients who underwent first LTx between 07/1991–02/2016 and were free from CLAD, were retrospectively classified according to PA presence in respiratory samples between 09/2011 and 09/2016. PA positive patients were subsequently stratified according to success of PA eradication following targeted antibiotic treatment. CLAD-free and graft survival were compared between PA positive and PA negative patients; and between patients with or without successful PA eradication. In addition, pulmonary function was assessed during the first year following PA isolation in both groups.ResultsCLAD-free survival of PA negative patients (n=443) was longer compared to PA positive patients (n=95) (p=0.045). Graft survival of PA negative patients (n=443, 82%) was better compared to PA positive patients (n=95, 18%) (p<0.0001). Similarly, PA eradicated patients demonstrated longer CLAD-free survival compared to patients with persistent PA (p=0.018). Pulmonary function was higher in successfully PA eradicated patients compared to unsuccessfully eradicated patients (p=0.035).ConclusionPA eradication after LTx improves CLAD-free and graft survival and maintains pulmonary function. Therefore, early PA detection and eradication should be pursued.

Detailed data on postoperative death in lung transplant (LTx) recipients are lacking. Therefore, we investigated all deaths after LTx in a large, single-centre, 25-year follow-up cohort. Prevalence, time, place and cause of death (COD) were retrospectively analysed for all patients undergoing primary LTx between July 1991 and December 2015 in our centre. Over subsequent years, postoperative survival significantly improved, with proportionally more patients surviving to 1-year post-LTx (P < 0.0001). A total of 347 (38.9%) LTx recipients died, of which 53.6% expired within 3 years post-LTx [median time to death 910 (236-2447) days]. Autopsy was performed in 34.8% of deaths. COD included CLAD in 27.1% (BOS 63.8% vs. RAS 36.2%); infection (26.5%); malignancy (15.6%); postoperative complication (11.2%); cardiovascular disease (4.6%) or other causes (6.9%). In 8.1%, no clear COD could be determined. COD significantly differed between the various LTx indications (P = 0.047). With longer follow-up, infection becomes a less prevalent COD, but CLAD and malignancies a more important COD. The majority of patients died on the intensive care unit (40.6%) or hospital ward (29.1%), but place of death varied depending on the underlying COD. The current study provides insights into the postoperative deaths of LTx recipients.