Postmortem brain 7T MRI with minimally invasive pathological correlation in deceased COVID-19 subjects

Background Brain abnormalities are a concern in COVID-19, so we used minimally invasive autopsy (MIA) to investigate it, consisting of brain 7T MR and CT images and tissue sampling via transethmoidal route with at least three fragments: the first one for reverse transcription polymerase chain reaction (RT-PCR) analysis and the remaining fixed and stained with hematoxylin and eosin. Two mouse monoclonal anti-coronavirus (SARS-CoV-2) antibodies were employed in immunohistochemical (IHC) reactions. Results Seven deceased COVID-19 patients underwent MIA with brain MR and CT images, six of them with tissue sampling. Imaging findings included infarcts, punctate brain hemorrhagic foci, subarachnoid hemorrhage and signal abnormalities in the splenium, basal ganglia, white matter, hippocampi and posterior cortico-subcortical. Punctate brain hemorrhage was the most common finding (three out of seven cases). Brain histological analysis revealed reactive gliosis, congestion, cortical neuron eosinophilic degeneration and axonal disruption in all six cases. Other findings included edema (5 cases), discrete perivascular hemorrhages (5), cerebral small vessel disease (3), perivascular hemosiderin deposits (3), Alzheimer type II glia (3), abundant corpora amylacea (3), ischemic foci (1), periventricular encephalitis foci (1), periventricular vascular ectasia (1) and fibrin thrombi (1). SARS-CoV-2 RNA was detected with RT-PCR in 5 out of 5 and IHC in 6 out 6 patients (100%). Conclusions Despite limited sampling, MIA was an effective tool to evaluate underlying pathological brain changes in deceased COVID-19 patients. Imaging findings were varied, and pathological features corroborated signs of hypoxia, alterations related to systemic critically ill and SARS-CoV-2 brain invasion.

5-ALA fluorescence in indeterminate grade gliomas

5-Aminolevulinic acid (5-ALA) is a useful and well-established adjunct for glioblastoma surgery. A growing body of evidence has revealed the potential utility of 5-ALA in grade II and grade III glioma patients as well. However, reliable means of identifying in whom fluorescence will occur have not been established. The authors report the case of such an indeterminate-grade glioma highlighting two pearls of 5-ALA fluorescence in this subgroup of patients. Firstly, 5-ALA–guided tissue sampling helps to ensure that the true grade of the lesion is not underestimated. Secondly, intraoperative fluorescence can serve as a prognostic marker. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21196

Advanced Bronchoscopic Technologies for Biopsy of the Pulmonary Nodule: A 2021 Review

The field of interventional pulmonology (IP) has grown from a fringe subspecialty utilized in only a few centers worldwide to a standard component in advanced medical centers. IP is increasingly recognized for its value in patient care and its ability to deliver minimally invasive and cost-effective diagnostics and treatments. This article will provide an in-depth review of advanced bronchoscopic technologies used by IP physicians focusing on pulmonary nodules. While most pulmonary nodules are benign, malignant nodules represent the earliest detectable manifestation of lung cancer. Lung cancer is the second most common and the deadliest cancer worldwide. Differentiating benign from malignant nodules is clinically challenging as these entities are often indistinguishable radiographically. Tissue biopsy is often required to discriminate benign from malignant nodule etiologies. A safe and accurate means of definitively differentiating benign from malignant nodules would be highly valuable for patients, and the medical system at large. This would translate into a greater number of early-stage cancer detections while reducing the burden of surgical resections for benign disease. There is little high-grade evidence to guide clinicians on optimal lung nodule tissue sampling modalities. The number of novel technologies available for this purpose has rapidly expanded over the last decade, making it difficult for clinicians to assess their efficacy. Unfortunately, there is a wide variety of methods used to determine the accuracy of these technologies, making comparisons across studies impossible. This paper will provide an in-depth review of available data regarding advanced bronchoscopic technologies.

Diagnostic Yield of Transbronchial Lung Cryobiopsy Compared to Transbronchial Forceps Biopsy in Patients with Sarcoidosis in a Prospective, Randomized, Multicentre Cross-Over Trial

Background: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis. Methods: In this post hoc analysis of a prospective, randomized, controlled, multicentre study, 359 patients with ILD requiring diagnostic bronchoscopic tissue sampling were included. TBLF and TBLC were both used for each patient in a randomized order. Histological assessment was undertaken on each biopsy and determined whether sarcoid was a consideration. Results: A histological diagnosis of sarcoidosis was established in 17 of 272 cases for which histopathology was available. In 6 out of 17 patients, compatible findings were seen with both TBLC and TBLF. In 10 patients, where the diagnosis of sarcoidosis was confirmed by TBLC, TBLF did not provide a diagnosis. In one patient, TBLF but not TBLC confirmed the diagnosis of sarcoidosis. Conclusions: In this post hoc analysis, the histological diagnosis of sarcoidosis was made significantly more often by TBLC than by TBLF. As in other idiopathic interstitial pneumonias (IIPs), the use of TBLC should be considered when sarcoidosis is suspected.

Does lateral arm technique decrease the rate of clip migration in stereotactic and tomosynthesis-guided biopsies?

Background Mammography-guided vacuum-assisted biopsies (MGVAB) can be done with stereotaxis or digital breast tomosynthesis guidance. Both methods can be performed with a conventional (CBA) or a lateral arm biopsy approach (LABA). Marker clip migration is relatively frequent in MGVAB (up to 44%), which in cases requiring surgery carries a risk of positive margins and re-excision. We aimed to compare the rates of clip migration and hematoma formation between the CBA and LABA techniques of prone MGVAB. Our HIPAA compliant retrospective study included all consecutive prone MGVAB performed in a single institution over a 20-month period. The LABA approach was used with DBT guidance; CBA utilized DBT or stereotactic guidance. The tissue sampling techniques were otherwise identical. Results After exclusion, 389 biopsies on 356 patients were analyzed. LABA was done in 97 (25%), and CBA in 292 (75%) cases. There was no statistical difference in clip migration rate with either 1 cm or 2 cm distance cut-off [15% for CBA and 10% for LABA for 1 cm threshold (p = 0.31); 5.8% or CBA and 3.1% or LABA for 2 cm threshold (p = 0.43)]. There was no difference in the rate of hematoma formation (57.5% in CDB and 50.5% in LABA, p = 0.24). The rates of technical failure were similar for both techniques (1.7% for CBA and 3% for LABA) with a combined failure rate of 1%. Conclusions LABA and CBA had no statistical difference in clip migration or hematoma formation rates. Both techniques had similar success rates and may be helpful in different clinical situations.

Validating a Minimally Invasive Tissue Sampling (MITS) Method in Determining Cause of Death in Stillbirths and Neonates

Complete diagnostic autopsy (CDA) remains the gold standard and a valuable technique for determining cause of death. It is a source of health statistics that can be used to measure health care services’ quality, unraveling important information on disease processes, particularly in emerging and unknown diseases. It can also be a vital tool for medical education and biomedical research. However, autopsy rates have been declining globally. There is an urgent need to develop and validate alternative methods in different settings to provide reliable information on cause of death. In this study, we aimed to determine cause of death (KazCoDe) in neonates and infants using minimally invasive tissue sampling (MITS), and to compare these results with those of CDA. We conducted MITS and CDA sequentially on 24 deceased children at the Pathological Bureau of the Akimat of the city of Nur-Sultan. Clinical data of the study subjects were extracted from their clinical records. During both procedures, brain, liver and lung tissues were collected for pathological diagnosis. Fifteen (62.5%) and nine (37.5%) were stillbirths and neonates, respectively. Eight (33.3%) were females and 16 (66.7%) were males. MITS diagnosis of cause of death was concordant with CDA diagnosis in 83.3% out of the 24 cases when considering the immediate and underlying causes of death and reviewing all the clinical and laboratory test results as part of the diagnostic evaluation to arrive at a cause of death (ICD-PM). We concluded that MITS is a valuable and reliable method for cause of death diagnosis in stillbirths and neonates, which can contribute vital mortality statistics in children in the absence of CDA.

Cell-free DNA technologies for the analysis of brain cancer

Survival for glioma patients has shown minimal improvement over the past 20 years. The ability to detect and monitor gliomas relies primarily upon imaging technologies that lack sensitivity and specificity, especially during the post-surgical treatment phase. Treatment-response monitoring with an effective liquid-biopsy paradigm may also provide the most facile clinical scenario for liquid-biopsy integration into brain-tumour care. Conceptually, liquid biopsy is advantageous when compared with both tissue sampling (less invasive) and imaging (more sensitive and specific), but is hampered by technical and biological problems. These problems predominantly relate to low concentrations of tumour-derived DNA in the bloodstream of glioma patients. In this review, we highlight methods by which the neuro-oncological scientific and clinical communities have attempted to circumvent this limitation. The use of novel biological, technological and computational approaches will be explored. The utility of alternate bio-fluids, tumour-guided sequencing, epigenomic and fragmentomic methods may eventually be leveraged to provide the biological and technological means to unlock a wide range of clinical applications for liquid biopsy in glioma.

Why parents agree or disagree for minimally invasive tissue sampling (MITS) to identify causes of death in under-five children and stillbirth in North India: a qualitative study

Background Information on exact causes of death and stillbirth are limited in low and middle income countries. Minimally invasive tissue sampling (MITS) is increasingly practiced in place of autopsy across several settings. A formative research documented the experiences of counselling and consenting for MITS in north India. Methods This exploratory qualitative study was conducted at a tertiary care hospital in Delhi. During the early implementation of MITS, observations of the counselling and consenting process (n = 13) for under-five child death and stillbirths were conducted. In-depth interviews with MITS team members (n = 3) were also conducted. Observation and interview data were transcribed and inductively analysed using thematic content analysis to identify emerging themes and codes. Results The MITS team participated in daily ward rounds for familiarisation with parents/families. Following death declaration the counselling was done in counselling corner of the ward or adjacent corridor. Mostly the counselling was targeted at the father and family members present, using verbal explanation and the consent document in local language. The key concerns raised by parents/family were possible disfigurement, time needed and possible benefits. Most of the parents consulted family members before consent. Among those who consented, desire for next pregnancy, previous pregnancy or neonatal loss and participation of treating senior doctor were the key factors. The negative experience of hospital care, poor comprehension and distance from residence were the factors for consent refusal. Lesser number of parents of deceased children consented for MITS compared to the neonates and stillbirths. Conclusions The initial experiences of obtaining consent for MITS were encouraging. Consent for MITS may be improved with active involvement of the treating doctors and nurses, better bereavement support, private counselling area along with improvement in quality of care and communication during hospitalisation. Special efforts and refinement in counselling are needed to improve consent for MITS in older children.

Is There an Increasing Incidence of Gastroesophageal Junctional Adenocarcinoma and Barrett Esophagus in Asia? A Review of Diagnostic Conundrums

<b><i>Background:</i></b> Epidemiology data of gastroesophageal junction (GEJ) cancers in Asia are extremely scarce. It is hardly registered by any cancer registry in the region, and only a few reports are available. Based on existing literature works, the overall trend indicates similar or gradually increasing GEJ cancers in Asia but comparably less than the West. The increasing trend in Asia is likely a result of rising risk factors, especially of gastroesophageal reflux disease and obesity. <b><i>Summary:</i></b> However, epidemiology data may be misleading due to several contentious diagnostic issues. The diagnostic conundrums are due to inherent complexity of the GEJ as a functional and pathological unit. Challenging diagnostic issues in Asia include the following: nonstandardized landmark of the GEJ, misclassification of Barrett esophagus, targeted versus nontargeted tissue sampling, histopathology disagreement and challenges in screening or surveillance of dysplastic BE and early GEJ cancer. The recent Asian-Pacific survey led by the Asian Barrett Consortium (ABC) has provided useful insights into these contentious issues. A key learning point from these diagnostic limitations is that the awareness of the disease and adherence to existing recommendations or guidelines are poor in the region. <b><i>Key Messages:</i></b> Standardization in diagnostic methodology is vital for accurate epidemiology data, and this can only come from better awareness and adherence through educational and international efforts. Last, surveillance strategy may need a paradigm shift from a purely diagnostic approach to a combined targeted surveillance and treatment approach using novel endoscopic techniques.