Immune signature of Chlamydia vaccine CTH522/CAF®01 translates from mouse-to-human and induces durable protection in mice.

The clinical development of an effective Chlamydia vaccine requires in-depth understanding of how well protective pre-clinical immune signatures translate to humans. Here, we report a comparative immunological characterization of CTH522/CAF®01 in female mice and humans. We find a range of immune signatures that translate from mouse to human, including a Th1/Th17 cytokine profile and antibody functionality. We identify vaccine-induced T cell epitopes, conserved among Chlamydia serovars, and previously found in infected individuals. Using the mouse model, we show that the common immune signature protected against ascending infection in mice, and vaccine induced antibodies could delay bacterial ascension to the oviduct, as well as development of pathology, in a T cell depleted mouse model. Finally, we demonstrate long-lasting immunity and protection of mice one year after vaccination. Based on the results obtained in the present study, we propose to further investigate CTH522/CAF®01 in a phase IIb study.

Subject-specific finite element head models for skull fracture evaluation-a new tool in forensic pathology.

Post-mortem computed tomography (PMCT) enables the creation of subject-specific 3D head models suitable for quantitative analysis such as finite element analysis (FEA). FEA of proposed traumatic events is an objective and repeatable numerical method for assessing whether an event could cause a skull fracture such as seen at autopsy. FEA of blunt force skull fracture in adults with subject-specific 3D models in forensic pathology remains uninvestigated. This study aimed to assess the feasibility of FEA for skull fracture analysis in routine forensic pathology. Five cases with blunt force skull fracture and sufficient information on the kinematics of the traumatic event to enable numerical reconstruction were chosen. Subject-specific finite element (FE) head models were constructed by mesh morphing based on PMCT 3D models and A Detailed and Personalizable Head Model with Axons for Injury Prediction (ADAPT) FE model. Morphing was successful in maintaining subject-specific 3D geometry and quality of the FE mesh in all cases. In three cases, the simulated fracture patterns were comparable in location and pattern to the fractures seen at autopsy/PMCT. In one case, the simulated fracture was in the parietal bone whereas the fracture seen at autopsy/PMCT was in the occipital bone. In another case, the simulated fracture was a spider-web fracture in the frontal bone, whereas a much smaller fracture was seen at autopsy/PMCT; however, the fracture in the early time steps of the simulation was comparable to autopsy/PMCT. FEA might be feasible in forensic pathology in cases with a single blunt force impact and well-described event circumstances.

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

Prediction of skull fractures in blunt force head traumas using finite element head models.

Traumatic head injuries remain a leading cause of death and disability worldwide. Although skull fractures are one of the most common head injuries, the fundamental mechanics of cranial bone and its impact tolerance are still uncertain. In the present study, a strain-rate-dependent material model for cranial bone has been proposed and implemented in subject-specific Finite Element (FE) head models in order to predict skull fractures in five real-world fall accidents. The subject-specific head models were developed following an established image-registration-based personalization pipeline. Head impact boundary conditions were derived from accident reconstructions using personalized human body models. The simulated fracture lines were compared to those visible in post-mortem CT scans of each subject. In result, the FE models did predict the actual occurrence and extent of skull fractures in all cases. In at least four out of five cases, predicted fracture patterns were comparable to ones from CT scans and autopsy reports. The tensile material model, which was tuned to represent rate-dependent tensile data of cortical skull bone from literature, was able to capture observed linear fractures in blunt indentation loading of a skullcap specimen. The FE model showed to be sensitive to modeling parameters, in particular to the constitutive parameters of the cortical tables. Nevertheless, this study provides a currently lacking strain-rate dependent material model of cranial bone that has the capacity to accurately predict linear fracture patterns. For the first time, a procedure to reconstruct occurrences of skull fractures using computational engineering techniques, capturing the all-in-all fracture initiation, propagation and final pattern, is presented.

A Virtual, 3D Multimodal Approach to Victim and Crime Scene Reconstruction.

In the last two decades, forensic pathology and crime scene investigations have seen a rapid increase in examination tools due to the implementation of several imaging techniques, e.g., CT and MR scanning, surface scanning and photogrammetry. These tools encompass relatively simple visualization tools to powerful instruments for performing virtual 3D crime scene reconstructions. A multi-modality and multiscale approach to a crime scene, where 3D models of victims and the crime scene are combined, offers several advantages. A permanent documentation of all evidence in a single 3D environment can be used during the investigation phases (e.g., for testing hypotheses) or during the court procedures (e.g., to visualize the scene and the victim in a more intuitive manner). Advanced computational approaches to understand what might have happened during a crime can also be applied by, e.g., performing a virtual animation of the victim in the actual context, which can provide important information about possible dynamics during the event. Here, we present an overview of the different techniques and modalities used in forensic pathology in conjunction with crime scene investigations. Based on our experiences, the advantages and challenges of an image-based multi-modality approach will be discussed, including how their use may introduce new visualization modalities in court, e.g., virtual reality (VR) and 3D printing. Finally, considerations about future directions in research will be mentioned.

Genetics of skeletal proportions in two different populations.

Human height can be divided into sitting height and leg length, reflecting growth of different parts of the skeleton whose relative proportions are captured by the ratio of sitting to total height (as sitting height ratio, SHR). Height is a highly heritable trait, and its genetic basis has been well-studied. However, the genetic determinants of skeletal proportion are much less well-characterized. Expanding substantially on past work, we performed a genome-wide association study (GWAS) of SHR in ∼450,000 individuals with European ancestry and ∼100,000 individuals with East Asian ancestry from the UK and China Kadoorie Biobanks. We identified 565 loci independently associated with SHR, including all genomic regions implicated in prior GWAS in these ancestries. While SHR loci largely overlap height-associated loci (P < 0.001), the fine-mapped SHR signals were often distinct from height. We additionally used fine-mapped signals to identify 36 credible sets with heterogeneous effects across ancestries. Lastly, we used SHR, sitting height, and leg length to identify genetic variation acting on specific body regions rather than on overall human height.

3D printed skulls in court - a benefit to stakeholders?

Forensic pathologists may use 3D prints as demonstrative aids when providing expert testimony in court of law, but the effects remain unclear despite many assumed benefits. In this qualitative study, the effects of using a 3D print, demonstrating a blunt force skull fracture, in court were explored by thematic analysis of interviews with judges, prosecutors, defence counsels, and forensic pathologists with the aim of improving the expert testimony. Five semi-structured focus groups and eight one-to-one interviews with a total of 29 stakeholders were transcribed ad verbatim and analysed using thematic analysis. The study found that a highly accurate 3D print of a skull demonstrated autopsy findings in detail and provided a quick overview, but sense of touch was of little benefit as the 3D print had different material characteristics than the human skull. Virtual 3D models were expected to provide all the benefits of 3D prints, be less emotionally confronting, and be logistically feasible. Both 3D prints and virtual 3D models were expected to be less emotionally confronting than autopsy photos. Regardless of fidelity, an expert witness was necessary to translate technical language and explain autopsy findings, and low-fidelity models may be equally suited as demonstrative aids. The court infrequently challenged the expert witnesses' conclusions and, therefore, rarely had a need for viewing autopsy findings in detail, therefore rarely needing a 3D print.

The intracranial pressure-volume relationship following decompressive hinge craniotomy compared to decompressive craniectomy-a human cadaver study.

OBJECTIVE: Decompressive hinge craniotomy (DHC) is an alternative treatment option to decompressive craniectomy (DC) for elevated intracranial pressure (ICP). The aim of this study was to characterize the difference in pressure-volume relationship between DHC and DC. METHODS: We compared the intracranial pressure-volume relationship in a human cadaver model following either DHC, DC, or fixing of the bone plate by titanium clamps. We inserted an intracranial expandable device in two human cadaver specimens, performed either DHC, DC, or bone plate fixation, and gradually increased the intracranial volume while measuring ICP. Following DHC, we also performed CT-scans at pre-defined intervals. RESULTS: Before ICP exceeded a threshold of 20 mmHg, a fixed bone plate tolerated an increase of 130 ml of intracranial volume, while DHC and DC allowed an increase of 190 ml and 290 ml, respectively. CT-derived calculations following DHC determined that the increase in intracranial volume at ICP 22 mmHg was 65 ml, the maximal increase of intracranial volume was 84 ml, the maximal bone displacement was 21 mm, and the bone plate volume to be 82 ml. Manual stress test of the hinged bone plate did not allow misalignment or intracranial displacement of the bone plate. CONCLUSION: DHC increases the intracranial volume by up to 84 ml and allows for approximately 60 ml increase of intracranial volume before ICP exceeds 20 mmHg. This indicates, when comparing with results from previous studies of herniation volumes, that DHC will be sufficient in many patients with head injury or cerebral infarction with treatment refractory intracranial hypertension.

Application of postmortem imaging modalities in cases of sudden death due to cardiovascular diseases-current achievements and limitations from a pathology perspective : Endorsed by the Association for European Cardiovascular Pathology and by the International Society of Forensic Radiology and Imaging.

Postmortem imaging (PMI) is increasingly used in postmortem practice and is considered a potential alternative to a conventional autopsy, particularly in case of sudden cardiac deaths (SCD). In 2017, the Association for European Cardiovascular Pathology (AECVP) published guidelines on how to perform an autopsy in such cases, which is still considered the gold standard, but the diagnostic value of PMI herein was not analyzed in detail. At present, significant progress has been made in the PMI diagnosis of acute ischemic heart disease, the most important cause of SCD, while the introduction of postmortem CT angiography (PMCTA) has improved the visualization of several parameters of coronary artery pathology that can support a diagnosis of SCD. Postmortem magnetic resonance (PMMR) allows the detection of acute myocardial injury-related edema. However, PMI has limitations when compared to clinical imaging, which severely impacts the postmortem diagnosis of myocardial injuries (ischemic versus non-ischemic), the age-dating of coronary occlusion (acute versus old), other potentially SCD-related cardiac lesions (e.g., the distinctive morphologies of cardiomyopathies), aortic diseases underlying dissection or rupture, or pulmonary embolism. In these instances, PMI cannot replace a histopathological examination for a final diagnosis. Emerging minimally invasive techniques at PMI such as image-guided biopsies of the myocardium or the aorta, provide promising results that warrant further investigations. The rapid developments in the field of postmortem imaging imply that the diagnosis of sudden death due to cardiovascular diseases will soon require detailed knowledge of both postmortem radiology and of pathology.

Investigation of Structural Alterations in Inherited Retinal Diseases: A Quantitative SD-OCT-Analysis of Retinal Layer Thicknesses in Light of Underlying Genetic Mutations.

Inherited retinal diseases can result from various genetic defects and are one of the leading causes for blindness in the working-age population. The present study aims to provide a comprehensive description of changes in retinal structure associated with phenotypic disease entities and underlying genetic mutations. Full macular spectral domain optical coherence tomography scans were obtained and manually segmented in 16 patients with retinitis pigmentosa, 7 patients with cone−rod dystrophy, and 7 patients with Stargardt disease, as well as 23 age- and sex-matched controls without retinal disease, to assess retinal layer thicknesses. As indicated by generalized least squares models, all IRDs were associated with retinal thinning (p < 0.001), especially of the outer nuclear layer (ONL, p < 0.001). Except for the retinal nerve fiber layer, such thinning was associated with a reduced visual acuity (p < 0.001). These advances in our understanding of ultrastructural retinal changes are important for the development of gene-, cell-, and optogenetic therapy. Longitudinal studies are warranted to describe the temporal component of those changes.

Sensitivity and specificity of post-mortem computed tomography in skull fracture detection-a systematic review and meta-analysis.

Post-mortem computed tomography (PMCT) has been increasingly used as routine examination in forensic pathology. No recent review of the growing number of papers on the ability of PMCT to detect skull fracture exists, and original papers report sensitivities from 0.85 to 1.00. This systematic review (PROSPERO: CRD42021233264) aims to provide a meta-analysis of sensitivity and specificity of PMCT in skull fracture detection. We searched PubMed, MEDLINE and Embase for papers published between January 2000 and August 2021 reporting raw numbers, sensitivity and specificity or Abbreviated Injury Score for PMCT compared to autopsy. Papers without both PMCT and autopsy, no separate reporting of the neuro-cranium, exclusively on children, sharp trauma, gunshot or natural death as well as case reports and reviews were excluded. Two authors independently performed inclusion, bias assessment and data extraction. QUADAS-2 was used for bias assessment and a random effects models used for meta-analysis. From 4.284 hits, 18 studies were eligible and 13 included in the meta-analysis for a total of 1538 cases. All deceased were scanned on multi-slice scanners with comparable parameters. Images were evaluated by radiologists or pathologists. Intra- and inter-observer analyses were rarely reported. In summary, sensitivity of PMCT for detection of fractures in the skull base was 0.87 [0.80; 0.92] with specificity 0.96 [0.90; 0.98], and sensitivity for the vault was 0.89 [0.80; 0.94] with specificity 0.96 [0.91; 0.98]. The mixed samples are a limitation of the review.

Fractures of the neuro-cranium: sensitivity and specificity of post-mortem computed tomography compared with autopsy.

Post-mortem computed tomography (PMCT) is a routine tool in many forensic pathology departments as it is fast and non-destructive and allows less gruesome visualization than photographs, and the images are indefinitely storable. Several studies investigated congruence between PMCT and autopsy for skull fracture but registered only the presence or absence of fracture systems. The objective of this study was to determine location-specific sensitivity and specificity of PMCT for individual fracture lines in blunt force head trauma. Accurate 3D models based on PMCT data with all fracture lines visible are important for future studies on fractures, applying finite element analysis (FEA). We retrospectively sampled adult cases from 2013 to 2019 with skull fracture mentioned in the autopsy report. PMCT was on a Siemens 64-slice scanner and autopsy according to international guidelines. The location and direction of all fracture lines at autopsy and at de novo interpretation of scans were registered and compared. Ninety-nine cases with 4809 individual findings were included. Age ranged from 18 to 100 years. The overall sensitivity was 0.58, and specificity was 0.91. For individual locations, sensitivity ranged from 0.24 to 0.85, and specificity ranged from 0.73 to 1.00. Intra-observer agreement was 0.74, and inter-observer agreement ranged from 0.43 to 0.58. In conclusion, PMCT is suited for detection of fracture systems, but not for detection of all individual fracture lines. Our results differed from the existing literature due to the methodological choices of registering individual fracture lines. Future studies utilising FEA must supplement PMCT with autopsy data.

4-PBA Treatment Improves Bone Phenotypes in the Aga2 Mouse Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetically heterogenous disorder most often due to heterozygosity for mutations in the type I procollagen genes, COL1A1 or COL1A2. The disorder is characterized by bone fragility leading to increased fracture incidence and long-bone deformities. Although multiple mechanisms underlie OI, endoplasmic reticulum (ER) stress as a cellular response to defective collagen trafficking is emerging as a contributor to OI pathogenesis. Herein, we used 4-phenylbutiric acid (4-PBA), an established chemical chaperone, to determine if treatment of Aga2+/- mice, a model for moderately severe OI due to a Col1a1 structural mutation, could attenuate the phenotype. In vitro, Aga2+/- osteoblasts show increased protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation protein levels, which improved upon treatment with 4-PBA. The in vivo data demonstrate that a postweaning 5-week 4-PBA treatment increased total body length and weight, decreased fracture incidence, increased femoral bone volume fraction (BV/TV), and increased cortical thickness. These findings were associated with in vivo evidence of decreased bone-derived protein levels of the ER stress markers binding immunoglobulin protein (BiP), CCAAT/-enhancer-binding protein homologous protein (CHOP), and activating transcription factor 4 (ATF4) as well as increased levels of the autophagosome marker light chain 3A/B (LC3A/B). Genetic ablation of CHOP in Aga2+/- mice resulted in increased severity of the Aga2+/- phenotype, suggesting that the reduction in CHOP observed in vitro after treatment is a consequence rather than a cause of reduced ER stress. These findings suggest the potential use of chemical chaperones as an adjunct treatment for forms of OI associated with ER stress. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Lethal small bowel obstruction due to pica.

Up to 25% of institutionalized patients with cognitive deficiencies display pica-like behavior, with an estimated annual incidence of small bowel obstruction of 2%. We present a case based on the forensic autopsy of a 41-year-old woman who died as a result of a missed diagnosis of small bowel obstruction after ingesting a foreign body. The case underlines the importance of precaution when treating patients with cognitive deficiency and/or language deficits and gastrointestinal symptoms. In such cases, it is important to employ a liberal threshold for radiological investigations and, if possible, obtain a medical history from a person close to the patient.

[Epidemiology and treatment of retinopathy of prematurity. The Hannover data in the Retina.net ROP registry from 2001-2017]. / Epidemiologie und Therapie der behandlungsbedürftigen Frühgeborenenretinopathie. Die Hannoveraner Daten im Retina.net ROP-Register von 2001 bis 2017.

BACKGROUND: The Retina.net ROP registry documents data of preterm infants developing stages of retinopathy of prematurity (ROP) that need ROP treatment. The aim of this analysis was to investigate data regarding epidemiology, therapy and changes over time (15 years) in a single participating center (Hannover Medical School, MHH). METHODS: Analysis of data of infants treated for ROP at a single center over time (birth 2001-2016, ROP treatment in 2002-2017). RESULTS: Overall, 65 infants were treated (23 female). In 11 infants (16.9%) ROP screening was conducted externally and infants were transferred to the MHH for ROP treatment. Between 2006 and 2016, incidence of ROP requiring treatment among infants screened for the development of ROP was 4.1%. Mean gestational age was 25.7 weeks (standard deviation, SD 1.8), mean birth weight 763 g (SD 235), postmenstrual age at treatment 38.2 weeks (SD 3.2), postnatal age 12.4 weeks (SD 3.2). There was no significant change in parameters over time. ROP zone II, stage 3+ was most frequently treated (57 eyes of 31 infants). 58 infants were treated with laser (114 eyes), 7 infants were treated with anti-VEGF (bevacizumab, bilateral, 14 eyes) from 2014 onwards. Retreatment due to recurrence of ROP was necessary in one infant after initial laser coagulation. Infants with ROP requiring treatment often presented with neonatal comorbidities, ventilation in more than 90%, bronchopulmonary dysplasia, and received transfusions. CONCLUSION: This is the first monocentric analysis over 15 years originating from the Retina.net ROP registry. In this cohort we see a change in ROP therapy from laser coagulation to anti-VEGF (bevacizumab) from 2014 onwards, demographic data and treatment parameters remained relatively stable over time.

The legal impact of forensic medical life-threatening danger assessment conclusions in cases of violent offense.

OBJECTIVE: The aim of this study was to examine the association between the legal outcome for suspected perpetrators and the forensic life-threatening danger assessments conducted as part of the clinical forensic medical examinations of victims with penetrating injuries. METHOD: From the Danish Central Crime Register, we retrieved the legal outcomes for suspected perpetrators linked to victims with penetrating injuries in a six-year period and compared the proportional distribution of forensic life-threatening danger assessment conclusions - no life-threatening danger (NLD), could have been in life-threatening danger (CLD), and life-threatening danger (LD) - with the legal outcomes. RESULTS: 326 victims were related to at least one identified suspected perpetrator with a legal outcome. When the forensic life-threatening danger assessments were more severe, an increased proportion of cases resulted in formal charges and, subsequently, conviction, than when the forensic life-threatening danger assessments were less severe. The percentage point differences between NLD, CLD, and LD were almost equal. CONCLUSION: Our results indicate that the forensic life-threatening danger assessments are associated with the legal outcome, as both the proportion of cases with formal charges and the proportion of cases with a conviction increased with the severity of the forensic life-threatening danger assessment conclusions.

Translational deep phenotyping of deaths related to the COVID-19 pandemic: protocol for a prospective observational autopsy study.

INTRODUCTION: The COVID-19 pandemic is an international emergency with an extreme socioeconomic impact and a high mortality and disease burden. The COVID-19 outbreak is neither fully understood nor fully pictured. Autopsy studies can help understand the pathogenesis of COVID-19 and has already resulted in better treatment of patients. Structured and systematic autopsy of COVID-19-related deaths will enhance the mapping of pathophysiological pathways, not possible in the living. Furthermore, it provides an opportunity to envision factors translationally for the purpose of disease prevention in this and future pandemics. This is the protocol for an autopsy study that offers an umbrella for deep and diverse investigations of COVID-19-related deaths, including a systematic investigation of 'long' COVID-19 by means of extensive and systematic tissue sampling. METHODS AND ANALYSIS: A COVID-19-specific autopsy algorithm has been created to cover all cases undergoing clinical or forensic autopsy in Denmark. The algorithm describes advanced tissue sampling and a translational analytical follow-up for deep phenotyping. The translational approach covers registry data, postmortem imaging, gross autopsy findings, microscopic organ changes, postmortem toxicology, postmortem biochemical investigation, microbiological profiling and immunological status at the time of death, and future research projects covering genetics and epigenetics on an organ level. ETHICS AND DISSEMINATION: This study has been approved by the Regional Ethics Committee of the Region of Greater Copenhagen (No: H-20078436) and the Danish Data Protection Agency (No: 2002-54-1080). Next of kin gave informed consent to research. The study results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: This study is purely observational and, as such, does not meet the criteria of the International Committee of Medical Journal Editors for clinical trials; thus, there is no need for registration in a database of research trials, such as clinical trials. To facilitate cooperation in research, provide transparency on case recruitment for publications to come and to avoid unnecessary duplicate work, we nevertheless wish to publish our protocol.

Possible Involvement of Central Nervous System in COVID-19 and Sequence Variability of SARS-CoV-2 Revealed in Autopsy Tissue Samples: A Case Report.

The case presented here illustrates that interdisciplinary teamwork can be essential for the understanding of the COVID-19 disease presentation and enlightening of the pathophysiology. A 60-year-old woman without any comorbidities, apart from overweight, was found dead in her apartment after 14 days of home isolation due to suspicion of COVID-19. A forensic autopsy was performed. This revealed severely condensed, almost airless, firm lungs, and the cause of death was severe acute respiratory distress syndrome-associated with COVID-19 (SARS-CoV-2). In addition, SARS-CoV-2 was detected with reverse transcription polymerase chain reaction (RT-PCR) in cerebrospinal fluid, lung tissue, and tracheal sample and specific antibodies for SARS-CoV-2 were detected in cerebrospinal fluid and serum. Subsequent sequencing of the SARS-CoV-2 virus showed variation in nucleotides at 3 sites between SARS-CoV-2 isolates recovered from the tracheal sample, cerebrospinal fluid, and tissues from both lungs, and phylogenetic analysis revealed that the spinal fluid sample differed the most from the other 3 samples. This case supports the hypothesis that SARS-CoV-2 may be neuroinvasive and cause central nervous system infection.

Autopsies in pandemics - a perspective on barriers and benefits. Is it time for a revival?

Influenza virus and coronavirus pandemics regularly sweep the globe, at great cost of health and economy. Our aim was to conduct a PubMed search for autopsy studies on influenza and coronavirus to investigate the contribution of autopsies during pandemics, focussing on autopsy methods and procedures and the role of autopsy findings in pandemics. The retrieved autopsy studies generally relied on microscopy, polymerase chain reaction (PCR), immunostaining and electron microscopy. Most were small and reported on lung effects, including diffuse alveolar damage (DAD), pneumonia and tracheobronchitis. Antibiotic therapy has diminished a role for bacterial pneumonia, whereas obesity is an emerging risk factor. Autopsy studies have provided new insights into coronavirus disease 2019 (COVID-19) treatments like anti-coagulative therapy. Unfortunately, autopsies during pandemics are hampered by lack of guidelines, facilities and expertise for handling potentially infectious corpses and by widely varying recommendations for personal protective equipment and procedures. The Department of Forensic Pathology, at the Forensic Institute, at the University of Copenhagen in Denmark has, in collaboration with the Department of Pathology, Rigshospitalet, Copenhagen, initiated a prospective observational study on COVID-19-related deaths encompassing postmortem imaging, standardized autopsy procedures/reporting and extensive tissue sampling for histological, chemical, microbiological and genetic analysis. The study involves a diverse array of research groups at the University of Copenhagen, and the clinical field.

Selective retina therapy (SRT) in patients with therapy refractory persistent acute central serous chorioretinopathy (CSC): 3 months functional and morphological results.

PURPOSE: Central serous chorioretinopathy (CSC) is a disease presenting with detachment of the neurosensory retina and characteristic focal leakage on fluorescein angiography. The spontaneous remission rate is 84% within 6 months. In this study, the efficacy of selective retina therapy (SRT) was examined in patients with therapy refractory persistent acute CSC defined by symptoms for at least 6 months and persistent subretinal fluid (SRF) despite eplerenone therapy. MATERIAL AND METHODS: This is a prospective, monocentric observational study in 17 eyes (16 patients, mean age 42 years, 2 female). SRT was performed with the approved R:GEN laser (Lutronic, South Korea), a micropulsed 527-nm Nd:YLF laser device, with a train of 30 pulses of 1.7 µs at 100-Hz repetition rate at the point of focal leakage determined by fluorescein angiography (FA) at baseline (BSL). Visits on BSL, week 4 (wk4), and week 12 (wk12) included best corrected visual acuity (BCVA, logMar), central retinal thickness (CRT) on spectral domain optical coherence tomography (SD-OCT), and FA. Statistical analysis was performed by pair-by-pair comparisons of multiple observations in each case with Bonferroni correction for multiple testing. (IBM SPSS Statistics 25®). RESULTS: Mean CRT at BSL was 387.69 ± 110.4 µm. CRT significantly decreased by 106.31 µm in wk4 (95%-KI: 21.42-191.2; p = 0.01), by 133.63 µm in wk12 (95%-KI: 50.22-217.03; p = 0.001) and by 133.81 µm (95%-KI: 48.88-218.75; p = 0.001) compared to BSL. Treatment success defined as complete resolution of SRF occurred at wk4 in 7/17 eyes (35.3%) and at wk12 in 10/17 eyes (58.8%). Re-SRT was performed in 7/17 eyes (41.2%) after an average of 107.14 ± 96.59 days. Treatment success after Re-SRT was observed in 4/6 eyes (66.6%, 12 weeks after Re-SRT). Mean BCVA did not change significantly from BSL to any later timepoint after adjusting for multiple testing. Notably, eyes with treatment success showed better BCVA at all timepoints and gained more letters compared to failures. CONCLUSION: Single or repetitive SRT may be an effective and safe treatment in 2 of 3 patients suffering from acute persistent CSC after 6 months of symptoms or more. We observed complete resolution of SRF in around 60% of eyes 12 weeks after first SRT treatment and also 12 weeks after Re-SRT treatment in eyes with persistent or recurrent SRF. Results on the long-term course after SRT are still pending.