Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease-19 (COVID-19). While SARS-CoV-2-triggered hyperinflammatory tissue-damaging and immunothrombotic ...responses are thought to be major causes of respiratory failure and death, how they relate to lung immunopathological changes remains unclear. Neutrophil extracellular traps (NETs) can contribute to inflammation-associated lung damage, thrombosis, and fibrosis. However, whether NETs infiltrate particular compartments in severe COVID-19 lungs remains to be clarified. Here we analyzed postmortem lung specimens from four patients who succumbed to COVID-19 and four patients who died from a COVID-19-unrelated cause. We report the presence of NETs in the lungs of each COVID-19 patient. NETs were found in the airway compartment and neutrophil-rich inflammatory areas of the interstitium, while NET-prone primed neutrophils were present in arteriolar microthrombi. Our results support the hypothesis that NETs may represent drivers of severe pulmonary complications of COVID-19 and suggest that NET-targeting approaches could be considered for the treatment of uncontrolled tissue-damaging and thrombotic responses in COVID-19.
To contribute to a precise and thorough knowledge of immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) and to emphasize the importance of this specific form of ...toxicity in terms of potential predictive value and long-term effects.
We report the first case of granulomatosis with polyangiitis (GPA) in a patient treated with an anti-Programmed Death protein-1 (PD-1) antibody for advanced non-small-cell lung cancer (NSCLC).
After a single dose of this drug the patient showed severe myositis associated with a high anti-PR3 anti-neutrophil cytoplasmic antibody titer. Discontinuation of the anti-PD-1 and introduction of corticoids led to a remission of the irAE. Regarding tumor a partial response was noted. A year later a neutrophilic, sterile pleural exudate and cutaneous lesions appeared with the pathological findings of neutrophilic vasculitis. Retreatment with corticoids induced a new remission of symptoms. It remains unclear whether GPA was preexisting and clinically silent but revealed by the use of ICI or primarily induced by this treatment. Conclusions: irAE are rare when anti-PD-1 antibodies are used in monotherapy. They present with a distinct clinical picture and temporal course and require specific treatment. Patients with irAE usually have a favorable oncological outcome.
Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are, however, rare. While ...folliculogenesis and spermatogenesis are generally orchestrated via different mechanisms, some genetic anomalies can impair both female and male gametogenesis. Minichromosome maintenance complex component 9 (MCM9) is involved in DNA repair and mutations of the
gene have been previously reported in females with premature ovarian insufficiency (POI).
is also an emerging cancer risk gene. We performed next-generation and Sanger sequencing of fertility and related genes and hormonal and imaging studies in a kindred whose members had POI and disordered spermatogenesis. We identified a homozygous pathogenic
variant, c.394C>T (p.Arg132*) in three sisters affected by POI due to ovarian dysgenesis and their brother who had normal pubertal development but suffered from non-obstructive azoospermia. Testicular biopsy revealed Sertoli cell-only testicular histopathology. No evidence of early onset cancer was found in the homozygotic family members, but they were all young (<30 years) at the time of the study. In the male patient the homozygous
variant led to normal pubertal development and hormonal levels but caused a Sertoli-cell-only syndrome with non-obstructive azoospermia. In the homozygous females studied, the clinical, hormonal, and gonadal phenotypes revealed ovarian dysgenesis consistent with previous reports. Active screening for potential colorectal and other cancer risks in the homozygotic
subjects has been instigated.
Gestational alloimmune liver disease has emerged as the major cause of antenatal liver injury and failure. It usually manifests as neonatal liver failure with hepatic and extrahepatic iron overload, ...a clinical presentation called neonatal hemochromatosis. We report on a newborn in whom fetal hepatomegaly was detected during pregnancy and who presented at birth with liver cirrhosis and mild liver dysfunction. Liver biopsy showed the absence of iron overload but strong immunostaining of hepatocytes for the C5b-9 complex, the terminal complement cascade neoantigen occurring specifically during complement activation by the immunoglobulin G-mediated classic pathway, which established the alloimmune nature of the hepatocyte injury. The infant survived with no specific therapy, and follow-up until 36 months showed progressive normalization of all liver parameters. This case report expands the recognized clinical spectrum of congenital alloimmune liver disease to include neonatal liver disease and cirrhosis, even in the absence of siderosis. Such a diagnosis is of utmost importance regarding the necessity for immunotherapy in further pregnancies to avoid recurrence of alloimmune injury.
Adrenal ganglioneuroma Maweja, Sylvie, M.D; Materne, Roland, M.D., Ph.D; Detrembleur, Nancy, M.D ...
The American journal of surgery,
11/2007, Letnik:
194, Številka:
5
Journal Article, Web Resource
Recenzirano
Abstract Background A 20-year-old man was referred after having been discovered a left adrenal incidentaloma. Characteristics on magnetic resonance imaging (MRI) suggested the diagnosis of adrenal ...ganglioneuroma or carcinoma. Pathological examination after adrenalectomy concluded it was an adrenal ganglioneuroma. We studied the characteristics of adrenal ganglioneuroma. Methods We retrospectively reviewed hormonal status, computed tomography and MRI features, and histological findings of our series of 8 adrenal ganglioneuromas. Results Specific features were: (1) no hormonal hypersecretion; (2) presence of calcifications, no vessel involvement; and a non-enhanced attenuation of less than 40 Hounsfield units on computed tomography; and (3) low non-enhanced T1-weighted signal, a slightly high and heterogeneous T2-weighted signal, and a late and gradual enhancement on dynamic MRI, especially if associated with a whorled pattern. Conclusions Even if many aggressive tumors share some of those radiological features, the presence of all or most of them must lead the clinician to consider the diagnosis of adrenal ganglioneuroma.
Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique, generating fluorescent light emission from the tissue of interest and allowing in vivo live imaging at a ...cellular level (“optical biopsies”).
To the best of our knowledge, this article is the first to present pCLE images during medical thoracoscopy. We present here 3 different patients referred for various health problems. A precise description of pleural cavity pCLE images after intravenous fluorescein injection (a fluorophore) together with corresponding macroscopical and histological studies is performed. This led to the diagnosis of normal pleura in one case, carcinomatous pleuritis in another case and a malignant mesothelioma in the third case.
We believe that optical biopsies could help clinicians to make an early diagnosis, thereby allowing rapid therapeutic intervention (talc pleurodesis for example). Furthermore, it could help to guide biopsies when affected zones are not obvious to macroscopic examination.
In a near future, new fluorophores could be developed to stain some pathophysiological processes, therapeutic targets, or enzymes activities bringing new insights in endoscopic pleural disease work-up.
•Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique.•pCLE allows in vivo live imaging at a cellular level (“optical biopsies”).•We present pictures of pCLE during medical thoracoscopy and a direct comparison between normal pleura and pleural carcinomatosis.•Our work shows a clear distinction between normal pleura and pleural carcinomatosis with pCLE.
Probe based confocal laser endomicroscopy (pCLE) is an optical imaging tool allowing live imaging of tissues at a cellular level. It remains experimental but its clinical value as a ...diagnostic/guiding tool is apparent. To address the lack of data in thoracic oncology and pleural diseases, we show the ability of pCLE during medical thoracoscopy to distinguish benign from malignant pleural involvement.
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ABSTRACT
Background and objective
Probe based confocal laser endomicroscopy (pCLE) is an optical imaging technique allowing live tissue imaging at a cellular level. Currently, this tool remains experimental. Two studies regarding pleural disease have been published and suggest that pCLE could be valuable for pleural disease investigations. However, normal and malignant pleural pCLE features remain unknown. Therefore, we conducted a prospective trial of pCLE during medical thoracoscopy to study and describe the malignant and benign pleural pCLE features.
Methods
Every patient >18 years referred to our department for medical thoracoscopy was eligible. Medical thoracoscopy was performed under sedation, allowing spontaneous breathing. Five millilitres of fluorescein (10%) was intravenously administrated 5 min before image acquisition. The pCLE was introduced through the working channel of the thoracoscope and gently placed on the parietal pleura to record videos. Afterwards, biopsies were performed on the corresponding sites. Malignant and benign pleural pCLE features were precisely described and compared using 11 preselected criteria.
Results
A total of 62 patients were included in the analysis including 36 benign and 26 malignant pleura. Among our preselected criteria, ‘abnormal tissue architecture’ and ‘dysplastic vessels’ were strongly associated with malignancies (100% and 85% ss, 721% and 74% sp, respectively) whereas, the ‘full chia seeds sign’ and ‘cell shape homogeneity’ were associated with benignity (36% and 56% ss, 100% and 70% sp, respectively). No study‐related adverse events occurred.
Conclusion
Benign and malignant pleural involvement have clearly distinct pCLE features.
Hemorrhagic cystitis (HC) with BK polyomavirus (BKPyV) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT) that may lead to severe discomfort for the patient and ...significant morbidity (urinary obstruction, increased transfusion requirements and prolonged hospitalization). So far, there is no clear consensus on how to manage this complication.
Here, we report a single-center case series of 9 patients (4 children and 5 adults) treated with cidofovir endovesical (EV) instillation(s) for BKPyV-HC after alloHCT. EV Cidofovir was administered at a dose of 5 mg/kg, for 1 to 3 instillations (with a minimum delay between 2 successive doses of 5 days).
Eight out of the 9 treated patients with EV Cidofovir achieved a complete resolution of HC after 1–3 instillation(s), without recurrence of symptomatic infection within the next 3 months. Only 1 adult patient did not improve after treatment and developed severe morbidity (emphysematous cystitis).
Although this single-center case series of EV cidofovir for BKPyV HC after alloHCT shows encouraging results, only large prospective studies will definitively establish the effectiveness of this therapy.
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