Liver Injury in Patients with COVID-19 without Underlying Liver Disease

SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and—where it is particularly challenging—on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19. Material and Methods: We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury. Based on medical history and previous laboratory test results, we excluded cases of underlying liver disease. The analysis involved a clinical course of COVID-19 in patients without underlying liver disease as well as the type and course of liver injury. Results: Signs and symptoms of liver injury were present in 20% of patients, mostly presenting as a mixed-type pattern of injury with less common cases of standalone hepatocellular (parenchymal) or cholestatic injury. The liver injury symptoms resolved at the end of inpatient treatment in 20% of cases. Sixteen patients died with no cases where liver injury would be deemed a cause of death. Conclusions: (1) Liver injury secondary to COVID-19 was mild, and in in 20%, the signs and symptoms of liver injury resolved by the end of hospitalization. (2) It seems that liver injury in patients with COVID-19 was not associated with a higher risk of mortality. (3) The underlying mechanism of liver injury as well as its sequelae are not fully known. Therefore, caution and further monitoring are advised, especially in patients whose liver function tests have not returned to normal values.

Blast-induced axonal degeneration in the rat cerebellum in the absence of head movement

Blast exposure can injure brain by multiple mechanisms, and injury attributable to direct effects of the blast wave itself have been difficult to distinguish from that caused by rapid head displacement and other secondary processes. To resolve this issue, we used a rat model of blast exposure in which head movement was either strictly prevented or permitted in the lateral plane. Blast was found to produce axonal injury even with strict prevention of head movement. This axonal injury was restricted to the cerebellum, with the exception of injury in visual tracts secondary to ocular trauma. The cerebellar axonal injury was increased in rats in which blast-induced head movement was permitted, but the pattern of injury was unchanged. These findings support the contentions that blast per se, independent of head movement, is sufficient to induce axonal injury, and that axons in cerebellar white matter are particularly vulnerable to direct blast-induced injury.

Outcome of non-cooled asphyxiated infants with under-recognised or delayed-onset encephalopathy

ObjectiveTo describe the clinical characteristics, MRI findings and neurodevelopmental outcome of infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who were not selected for therapeutic hypothermia (TH).DesignRetrospective cohort study.Setting and patients(Near-)term infants with documented perinatal asphyxia referred to two Dutch level III neonatal units with neonatal encephalopathy (NE) and seizures <24 hours after birth not treated with TH. Infants with a diagnosis other than NE following perinatal asphyxia causing the seizures were excluded.Main outcome measuresClinical characteristics, findings on cranial MRI performed within 8 days after birth and neurodevelopmental outcome assessed using the Griffiths Mental Development Scales at 18 months or Bayley Scales of Infant and Toddler Development–Third Edition at 2 years of age.Results39 infants were included. All had abnormalities on MRI. Predominant white matter/watershed injury was the most common pattern of injury, 23 (59%). 7 (18%) infants had predominant basal ganglia/thalamus injury, 3 (8%) near total brain injury, 5 (13%) arterial ischaemic stroke, 1 (3%) an intraventricular haemorrhage. Adverse outcome was seen in 51%: 6 died, 11 developed cerebral palsy (spastic n=8, dyskinetic n=3), 2 had neurodevelopmental delay, 1 had severe hearing impairment.ConclusionsAll infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who did not receive TH had abnormalities on MRI. 51% had an adverse outcome. Better methods for recognition of infants who might benefit from TH and careful neurodevelopmental follow-up are urgently needed.

Both Bone Forearm Fracture with Complex DRUJ Dislocation: What Are the Odds?

Background Distal radioulnar joint (DRUJ) dislocation can occur as an isolated injury or in association with fracture radius (Galeazzi fracture-dislocation), Essex–Lopresti lesion or, rarely, with fracture of both radius and ulna (termed “Galeazzi type fracture”). DRUJ dislocations can be simple or complex. While simple DRUJ dislocation can be reduced by closed methods once the associated fractures are fixed anatomically, complex dislocation does not reduce by closed means. A complex DRUJ dislocation occurring in a both bone forearm fracture is an extremely unusual pattern of injury. Case Description We describe the clinical presentation, intraop findings, management, and follow-up of two such cases of both bone forearm fracture with complex DRUJ dislocation. In both the cases, the ulnar head was found to be buttonholed through extensor retinaculum between the extensor tendons. Open reduction had to be done via dorsal approach. Timely intervention allowed good results in both the patients. Literature Review Several authors have reported simple DRUJ dislocations in both bone forearm fractures; however, we could come across only three cases of complex DRUJ dislocation in a both bone forearm fracture. A summary of various series and reports on these injuries is presented. Case Relevance Through this case report, we want to highlight this unusual association and emphasize on sequence of fixation, so that this perilous injury pattern is not missed, and favorable outcomes could be obtained through appropriate and timely intervention.

Gunshot injury in children: A 3-year review of cases that presented to the Jos University Teaching Hospital, North Central Nigeria

Objectives: Gunshot injuries among children are a major clinical and public health concern and one of the leading causes of pediatric morbidity and mortality. This usually takes a great financial and emotional toll on the affected children, their families, and society as a whole. The objective of the study was to determine the pattern of injury, severity, outcome, and challenges in managing the gunshot injuries in children. Material and Methods: This is a descriptive study of patients below 18 years of age who presented with gunshot injuries to the Jos University Teaching Hospital between January 2011 and December 2014. Patient demographics and clinical details were collected on a trauma data sheet, and entered into an Excel spreadsheet. It was analyzed descriptively. Results: Two hundred and forty-two patients presented with gunshot injuries in the period under review, of which 30 of them were children. The median age of the patients was 12 years with an interquartile range of 7.75 and 16.25. Twenty-two (73.3%) of them were male while 8 (26.7%) were female. High-velocity firearms accounted for 13 (43.3%) of the injuries and were the most predominant cause of injury. The most common part of the body involved was the extremities in 63.3% of patients. Debridement and secondary suturing was carried out in 83.3% of the patients while wound infection was the most noted complication in 33.3% of the patients. Conclusion: There is an increasing incidence of gunshot injuries in this region. A lot of the children survive and reach the hospital though, and most of them are treated and discharged, however, attendant emotional and psychological trauma cannot be excluded in these patients. There is, thus, a need for proper policy to protect and treat these children when this happens.

Long-term cognitive outcomes in term newborns with watershed injury caused by neonatal encephalopathy

Background We previously reported that increasing severity of watershed (WS) injury in neonatal magnetic resonance imaging (MRI) is associated with worse language outcomes in early childhood. In the present study, we investigated the relationship between neonatal injury patterns and cognitive profile in adolescents with neonatal encephalopathy. Methods Term neonates with encephalopathy were prospectively enrolled and imaged using brain MRI from 1999 to 2008. Neonatal brain injury was scored according to the degree of injury in WS and basal ganglia/thalamus (BG/T) areas. The children underwent a neurocognitive assessment and follow-up brain MRI at the age of 10–16 years. The relationship between neonatal brain injury patterns and adolescent cognitive outcomes was assessed. Results In a cohort of 16 children, neonatal MRI showed WS injury in 7, BG/T injury in 2, and normal imaging in 7. Children with WS injury had lower estimated overall cognitive ability than those with normal imaging. Increasing WS injury score was associated with decreasing estimated overall cognitive ability, Perceptual Reasoning Index, and digit span score. Conclusions Children with the WS injury are at an increased risk of having problems in long-term intellectual ability. These cognitive outcomes may underlie early language difficulties seen in children with neonatal WS injury. Impact Adolescents with a history of neonatal encephalopathy and watershed pattern of injury on neonatal brain magnetic resonance imaging (MRI) had lower overall cognitive ability, perceptual reasoning skills, and auditory working memory than those with normal neonatal imaging. Children with post-neonatal epilepsy and cerebral palsy had the worst cognitive outcomes. Watershed pattern of injury confers high long-term differences in intellectual ability.

Neurotoxic Agents and Peripheral Neuropathy

Neurotoxicity may develop with exposure to various substances such as antibiotics, chemotherapeutics, heavy metals, and solvents. Some plants and fungi are also known to be neurotoxic. Neurotoxicity can develop acutely within hours, or it can develop as a result of exposure for years. Neurotoxicity can be presented with central or peripheral nervous system findings such as neurobehavioral symptoms, extrapyramidal signs, peripheral neuropathy. Peripheral nerve fibers are affected in different ways by neurotoxicant injury. The pattern of injury depends on the target structure involved. The focus of this chapter includes signs, symptoms, pathophysiology, and treatment options of neurotoxicity.

An Autopsy-Based Analysis of Fatal Road Traffic Collisions: How the Pattern of Injury Differs with the Type of Vehicle

In Italy, in only 2018, 3310 people died in road traffic accidents, more than in any other European country. Since the revelation of this occurrence, the authors carried out an analysis aimed at investigating if there was a difference in the injury patterns among different road users. A retrospective post-mortem study on road traffic fatalities was performed, which had been autopsied at the Institute of Forensic Medicine of Milan. First, the authors analyzed the epidemiological data of all the 1022 road traffic accidents subjected to an autopsy from 2007 to 2019. Secondly, further analysis of individual autopsy reports was carried out. For this purpose, 180 autopsies belonging to 5 different categories were analyzed: car, pedestrian, motorbike, bicycle, and truck. Seventy-six percent of road traffic fatalities were male, 54% were between 10 and 49 years of age, and 62% of the patients died before arriving at a hospital. “Multiple injuries” was the main cause of death. Traumatic brain injuries were particularly high in pedestrians and cyclists. In car, motorbike, and truck fatalities, thoracic and abdominal injuries were the most frequent. Therefore, pedestrians and cyclists had a higher prevalence for traumatic head injuries, while car, motorcycle, and truck occupants, on the other hand, had a higher prevalence for thoracic and abdominal injuries.

Cytokeratin 7 and Copper Stains Facilitate Diagnosis of Small Duct Primary Sclerosing Cholangitis

Introduction/Objective Classic primary sclerosing cholangitis (PSC) involves extrahepatic and/or intrahepatic biliary ducts with segmental biliary strictures and dilatations that often allow the diagnosis to be made via cholangiogram. Small duct PSC (sdPSC) is a rare subtype that presents similarly with a cholestatic pattern of injury, yet due to the small size of involved ducts, a cholangiogram is non-diagnostic and diagnosis is dependent on clinical suspicion and liver biopsy. The histopathological features of sdPSC are often subtle and may easily be overlooked. Diagnosis of this entity- though difficult- is important, as early recognition can facilitate the identification of associated disease processes and life-threatening complications. Methods/Case Report We encountered a 33-year-old female presenting with intermittent pruritis, episodes of jaundice, and persistently elevated alkaline phosphatase who was misdiagnosed with only fatty liver at an outside institution. Evaluation with MRCP showed no abnormalities within the biliary tract and a liver biopsy was performed to aid in the diagnosis. The H&E and trichrome findings of atrophic bile ducts and some peribiliary sclerosis were extremely subtle and may have been overlooked without clinical suspicion. Cytokeratin 7 (CK7) highlighted cholangiolar metaplasia in hepatocytes and the bile ductular reaction that occurs in cholestatic disease states. A Rhodamine copper stain showed periportal deposition suggestive of chronic biliary obstruction. Use of CK7 and copper stains supported the presence of chronic biliary injury and suboptimal bile flow, confirming the diagnosis of sdPSC. Results (if a Case Study enter NA) NA Conclusion Diagnosis of sdPSC has historically relied on H&E and trichrome stains. In this case, the findings on H&E and trichrome stains were non-diagnostic, while the use of CK7 and copper stains confirmed the diagnosis of sdPSC. We recommend using CK7 and copper stains to evaluate for sdPSC.

Secondary sclerosing cholangitis: a lesser known side effect of pembrolizumab therapy

Introduction/Objective Immune check-point inhibitors have increasingly taken hold as mainstays of various cancer treatments, revolutionizing outcomes for individuals diagnosed with terminal malignancy. Hepatotoxicity is reported to occur in 2-10% patients, predominantly manifesting as a mixed cholestatic hepatitis pattern of injury. Cholangitis is a rare immune-mediated adverse event (irAE). We present a case of pembrolizumab-induced secondary sclerosing cholangitis presenting with multiple biliary strictures. Early recognition is crucial as these cases are resistant to treatment with steroids. Methods/Case Report 82-year-old woman with recurrent, metastatic, high grade urothelial carcinoma status post cystectomy and neoadjuvant chemotherapy, presented with new onset obstructive jaundice (alkaline phosphatase 958 U/L, aspartate aminotransferase of 331 U/L, alanine aminotransferase of 422 U/L, and total bilirubin of 19.8 mg/dL) following two weeks of pembrolizumab therapy. MRCP suggested intrahepatic biliary ductal dilation. ERCP showed multiple strictures involving hepatic bifurcation, left, right and intrahepatic ducts with beaded intrahepatic bile ducts. Liver biopsy showed expanded portal tracts with mixed inflammatory infiltrate, extensive bile duct injury, neutrophilic cholangitis, ductular proliferation, and perivenular cholestasis (10% dropout) concerning for mechanical obstruction. CK7 did not show ductopenia and immunostain IgG4 was negative. All autoimmune work-up was negative. Liver enzymes continued to rise despite multiple therapeutic stents, drains, high-dose corticosteroids, ursodiol and mycophenolate mofetil. The patient died five months later. Results (if a Case Study enter NA) NA Conclusion Pemrolizumab-induced secondary sclerosing cholangitis is a rare, hence under-recognized, adverse effect of check point inhibitor-mediated hepatotoxicity. It is important to recognize this association, as it has limited benefit from steroid therapy. Our finding of pembrolizumab-related SC adds to the growing body of literature of immune check-point inhibitor-related hepatobiliary injury and calls for further characterization of PD-1/PD-L1 inhibitor SC and its clinical implications.