The State of the Do-Not-Resuscitate Order in a Pediatric Intensive Care Unit in the Middle East: A Retrospective Study

Objectives The Do-Not-Resuscitate (DNR) order is part of most hospitals’ policies on the process of making and communicating decisions about a patient's resuscitation status. Yet it has not become a part of our society's ritual of dying in the Middle East especially among children. Given the diversity of pediatric patients, the DNR order continues to represent a challenge to all parties involved in the care of children including the medical team and the family. Methods This was a retrospective review of the medical charts of patients who had died in the pediatric intensive care unit (PICU) of a tertiary academic institution in Beirut, Lebanon within the period of January 2012 and December 2017. Results Eighty-two charts were extracted, 79 were included in the analysis. Three were excluded as one patient had died in the Emergency Department (ED) and 2 charts were incomplete. Most patients were male, Lebanese, and from Muslim families. These patients clinically presented with primary cardiac and oncological diseases or were admitted from the ED with respiratory distress or from the operating room for post-operative management. The primary cause of death was multiorgan failure and cardiac arrest. Only 34% of families had agreed to a DNR order prior to death and 10% suggested “soft” resuscitation. Most discussions were held in the presence of the parents, the PICU team and the patient's primary physician. Conclusions The DNR order presents one of the most difficult challenges for all care providers involved, especially within a culturally conservative setting such as Lebanon. As the numbers suggest, it is difficult for parents to reach the decision to completely withhold resuscitative measures for pediatric patients, instead opting for “soft” resuscitations like administering epinephrine without chest compressions.

Odontogenic Cervicofacial Necrotizing Fasciitis: Microbiological Characterization and Management of Four Clinical Cases

Necrotizing fasciitis of the head and neck is a rare, very severe disease, which, in most cases, originates from odontogenic infections and frequently ends with the death of the patient. Rapid surgical intervention in combination with a preferably pathogen-specific antibiotic therapy can ensure patients’ survival. The question arises concerning which pathogens are causative for the necrotizing course of odontogenic inflammations. Experimental 16S-rRNA gene analysis with next-generation sequencing and bioinformatics was used to identify the microbiome of patients treated with an odontogenic necrotizing infection and compared to the result of the routine culture. Three of four patients survived the severe infection, and one patient died due to septic multiorgan failure. Microbiome determination revealed findings comparable to typical odontogenic abscesses. A specific pathogen which could be causative for the necrotizing course could not be identified. Early diagnosis and rapid surgical intervention and a preferably pathogen-specific antibiotic therapy, also covering the anaerobic spectrum of odontogenic infections, are the treatments of choice. The 16S-rRNA gene analysis detected significantly more bacteria than conventional methods; therefore, molecular methods should become a part of routine diagnostics in medical microbiology.

Ferrets are valuable models for SARS-CoV-2 research

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an ongoing pandemic with millions of deaths worldwide. Infection of humans can be asymptomatic or result in fever, fatigue, dry cough, dyspnea, and acute respiratory distress syndrome with multiorgan failure in severe cases. The pathogenesis of COVID-19 is not fully understood, and various models employing different species are currently applied. Ferrets can be infected with SARS-CoV-2 and efficiently transmit the virus to contact animals. In contrast to hamsters, ferrets usually show mild disease and viral replication restricted to the upper airways. Most reports have used the intranasal inoculation route, while the intratracheal infection model is not well characterized. Herein, we present clinical, virological, and pathological data from young ferrets intratracheally inoculated with SARS-CoV-2. Infected animals showed no significant clinical signs, and had transient infection with peak viral RNA loads at 4 days postinfection, mild to moderate rhinitis, and pulmonary endothelialitis/vasculitis. Viral antigen was exclusively found in the respiratory epithelium of the nasal cavity, indicating a particular tropism for cells in this location. Viral antigen was associated with epithelial damage and influx of inflammatory cells, including activated neutrophils releasing neutrophil extracellular traps. Scanning electron microscopy of the nasal respiratory mucosa revealed loss of cilia, shedding, and rupture of epithelial cells. The currently established ferret SARS-CoV-2 infection models are comparatively discussed with SARS-CoV-2 pathogenesis in mink, and the advantages and disadvantages of both species as research models for zoonotic betacoronaviruses are highlighted.

Spontaneous Intracerebral Hemorrhage (ICH) associated with pregnancy and SARS-CoV-2 infection: a case report

Background Coronavirus Disease 2019 (COVID-19) is predominately known as a respiratory disease associated with pneumonia, acute respiratory distress syndrome and multiorgan failure. However, extra-pulmonary complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly being recognized. In this regard, some studies implied the hemostatic and vascular involvements in patients with SARS-CoV-2 infection. Case presentation We describe a case of spontaneous Intracerebral Hemorrhage (ICH) in a pregnant patient with COVID-19 and history of cesarean section a week before the occurrence of ICH. The patient underwent emergent craniotomy with acceptable outcome. Hemorrhagic events, including ICH, may happen during COVID-19 infection with several possible mechanisms. Conclusion COVID-19 patients, especially high-risk groups, are at a risk of intracranial hemorrhage. Therefore, close follow-up must be maintained and hemorrhagic events must be kept in mind in these cases.

Risk Factors Associated with Mortality in Severe Chest Trauma Patients Admitted to the ICU

Our objective was to determine outcomes of severe chest trauma admitted to the ICU and the risk factors associated with mortality. An observational, prospective, and multicenter registry of trauma patients admitted to the participating ICUs (March 2015–December 2019) was utilized to collect the patient data that were analyzed. Severe chest trauma was defined as an Abbreviated Injury Scale (AIS) value of ≥3 in the thoracic area. Logistic regression analysis was used to evaluate the contribution of severe chest trauma to crude and adjusted ORs for mortality and to analyze the risk factors associated with mortality. Overall, 3821 patients (39%) presented severe chest trauma. The sample’s characteristics were as follows: a mean age of 49.88 (19.21) years, male (77.6%), blunt trauma (93.9%), a mean ISS of 19.9 (11.6). Crude and adjusted (for age and ISS) ORs for mortality in severe chest trauma were 0.78 (0.68–0.89) and 0.43 (0.37–0.50) (p < 0.001), respectively. In-hospital mortality in the severe chest trauma patients without significant traumatic brain injury (TBI) was 5.63% and was 25.71% with associated significant TBI (p < 0.001). Age, the severity of injury (NISS and AIS-head), hemodynamic instability, prehospital intubation, acute kidney injury, and multiorgan failure were risk factors associated with mortality. The contribution of severe chest injury to the mortality of trauma patients admitted to the ICU was very low. Risk factors associated with mortality were identified.

A Unique Case of Multicentric Infantile Myofibromatosis with Radiologic-Pathologic Correlation

Infantile myofibromatosis (IM) is a rare condition with a variable clinical presentation that characteristically affects young children. Most frequently it presents as one or more benign nodules of the skin, bones, soft tissues, or, rarely, visceral organs. According to the location and number of lesions, there are three different forms: solitary, multicentric without visceral involvement, and multicentric with visceral involvement (generalised), with the latter having the least favourable prognosis. We present a unique case of severe congenital generalised IM in a new-born male who required intubation and mechanical ventilation immediately after the birth due to respiratory distress. A chest radiograph showed numerous tumours involving the entire lung, resembling a metastatic lung disease. Additionally, the neonate had multiple, bluish, papular skin nodules and a biopsy of a skin nodule ultimately led to the diagnosis of IM. Diffuse lung involvement prevented adequate ventilation which resulted in multiorgan failure and death before targeted treatment could have been initiated. The presented case is unique, as such atypical extensive involvement of the lung and leptomeninges in IM has not been reported before. In this brief report, we present the findings of radiographic and ultrasonographic examinations in correlation with autopsy and histopathology.

Serum Ferritin Concentration in Corona Virus Disease 19

Introduction: Coronavirus disease 19 (COVID-19) is a complex disease responsible for the development of exacerbated inflammatory response (cytokine storm) that ultimately leads to multiorgan failure and death. Serum ferritin has been recently identified as one of the inflammatory markers responsible for the pro-inflammatory effects. Small amount of ferritin is present in plasma (15-150 ng/mL) which might increase with the severity of COVID-19. Therefore, measurement of ferritin is essential in identifying disease severity and predict disease prognosis. Objective: This study aims to assess the ferritin level in COVID-19 patients. Methods: A cross-sectional study was carried out on 259 COVID-19 patients visiting KIST Medical College and Teaching Hospital (KISTMCTH), Lalitpur, Nepal from November 2020 to April 2021. Serum ferritin was estimated in the automated Siemens ADVIA Centaur CP Chemiluminescence Immunoassay system. All the patients visiting KISTMCTH referred by clinician for ferritin assessment were included in this study. Data collected using the proforma tool was tabulated in SPSS 21 and statistical analysis was done by inferential statistical test. Results: Out of total 259 COVID-19 patients, 58.7% were male and the majority of patients (82.6%) were below 70 years of age. The mean age for all participants was 52.11±16.59 years. Hyperferritinemia was seen in 218 (84.16%) COVID -19 patients. The mean value of serum ferritin was 767.1±789.86 (IQR: 12.8-4590) ng/mL and was significantly higher in males (p<0.001). Comparing the mean values of ferritin between the patients below and above 70 years, no statistical difference was observed (p=0.872). Conclusions: In our study, serum ferritin levels were greatly increased in patients with COVID-19 infection. Keywords: Coronavirus disease 19; cytokine storm; inflammatory marker; serum ferritin.

A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune–epithelial interface

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled, by in vitro coculture, the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV-2–specific inflammatory gene cluster distinct from that seen in influenza A or Ebola virus-infected cocultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV-2 proteins (Spike and some nonstructural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV-2 induces in epithelia.

Familial Hemophagocytic Lymphohistiocytosis Secondary to PRF1 Mutation

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that causes systemic inflammation which can progress to multiorgan failure and death. Symptoms and signs commonly seen in HLH include high fever, hepatosplenomegaly, pancytopenia, and hypertriglyceridemia. This report describes the 8-month clinical course of a 17-year-old male with G6PD deficiency who presented with intermittent high fever of unknown origin for 8 months accompanied by pancytopenia and bilateral lower limb weakness. A pathogenic homozygous missense mutation (c.1081A > T p.(Arg361Trp)) in the PRF1 gene was detected by whole exome sequencing (WES). The brain and the whole spine MRI showed leptomeningeal enhancement at different levels involving both the brain and the spine. Therefore, a diagnosis of familial HLH type 2 with CNS involvement was confirmed. Accordingly, treatment with dexamethasone, cyclosporin, and etoposide in addition to intrathecal methotrexate and hydrocortisone was given. The patient showed a dramatic response with significant neurological improvement of the bilateral lower limb weakness. Genetic analysis has helped the patient’s family with appropriate genetic counselling. This case highlights the importance of immediate treatment with immunosuppressants and the high clinical suspicion of physicians regarding HLH in areas where consanguinity is common.