Cause Of Severe Morbidity Research Articles

Intravenous ketamine for emergency department treatment of suicidal ideation in a paediatric population: protocol for a double-blind, randomised, placebo-controlled, parallel-arm pilot trial (KSI study)

IntroductionSuicidal ideation (SI) is a common and severe cause of morbidity in adolescents. Patients frequently present to the emergency department (ED) for care, yet there is no acute therapeutic intervention...

Terminally exhausted CD8+ T cells contribute to age-dependent severity of respiratory virus infection

BackgroundLower respiratory infections are a leading cause of severe morbidity and mortality among older adults. Despite ubiquitous exposure to common respiratory pathogens throughout life and near universal seropositivity, antibodies fail to effectively protect the elderly. Therefore, we hypothesized that severe respiratory illness in the elderly is due to deficient CD8+ T cell responses.ResultsHere, we establish an aged mouse model of human metapneumovirus infection (HMPV) wherein aged C57BL/6 mice exhibit worsened weight loss, clinical disease, lung pathology and delayed viral clearance compared to young adult mice. Aged mice generate fewer lung-infiltrating HMPV epitope-specific CD8+ T cells. Those that do expand demonstrate higher expression of PD-1 and other inhibitory receptors and are functionally impaired. Transplant of aged T cells into young mice and vice versa, as well as adoptive transfer of young versus aged CD8+ T cells into Rag1−/− recipients, recapitulates the HMPV aged phenotype, suggesting a cell-intrinsic age-associated defect. HMPV-specific aged CD8+ T cells exhibit a terminally exhausted TCF1/7− TOX+ EOMES+ phenotype. We confirmed similar terminal exhaustion of aged CD8+ T cells during influenza viral infection.ConclusionsThis study identifies terminal CD8+ T cell exhaustion as a mechanism of severe disease from respiratory viral infections in the elderly.

Significant number of Plasmodium vivax mono-infections by PCR misidentified as mixed infections (P. vivax/P. falciparum) by microscopy and rapid diagnostic tests: malaria diagnostic challenges in Ethiopia

BackgroundPlasmodium vivax malaria is now recognized as a cause of severe morbidity and mortality, resulting in a substantial negative effect on health especially in endemic countries. Accurate and prompt diagnosis and treatment of P. vivax malaria is vital for the control and elimination of the disease.MethodsA cross-sectional study was conducted from February 2021 to September 2022 at five malaria endemic sites in Ethiopia including Aribaminch, Shewarobit, Metehara, Gambella, and Dubti. A total of 365 samples that were diagnosed positive for P. vivax (mono and mixed infection) using RDT, site level microscopists and expert microscopists were selected for PCR. Statistical analyses were performed to calculate the proportions, agreement (k), frequencies, and ranges among different diagnostic methods. Fisher’s exact tests and correlation test were used to detect associations and relationship between different variables.ResultsOf the 365 samples, 324 (88.8%), 37(10.1%), 2 (0.5%), and 2 (0.5%) were P. vivax (mono), P. vivax/Plasmodium falciparum (mixed), P. falciparum (mono) and negative by PCR, respectively. The overall agreement of rapid diagnostic test (RDT), site level microscopy and expert microscopists result with PCR was 90.41% (k: 0.49), 90.96% (k: 0.53), and 80.27% (k: 0.24). The overall prevalence of sexual (gametocyte) stage P. vivax in the study population was 215/361 (59.6%). The majority of these 215 samples (180; 83.7%) had below 1000 parasites/µl, with only four samples (1.9%) had ≥ 5000 parasites/µl. The gametocyte density was found to be weakly positive but statically significant with asexual parasitaemia (r = 0.31; p < 0.001).ConclusionBoth microscopy and RDT showed moderate agreement with PCR in the detection and identification of P. vivax (mono) and P. vivax/P. falciparum (mixed) infections. Therefore, to achieve malaria elimination goals, strengthening routine malaria diagnostic methods by implementing diagnostic tools with a good performance in detecting and accurately identifying malaria species in clinical settings is recommended.

Chiari Malformation with Surgically Induced Open Neural Tube Defect in Late Chick Embryos : Characterization by Magnetic Resonance Imaging and Histopathological Analysis.

Chiari II malformation (CM II) is still the main cause of severe morbidity and mortality in children with open neural tube defects (ONTDs). The goal of this study was to validate a CM II model in late-stage chick embryos with surgically induced ONTDs. To make the chick embryo model of ONTD, their neural tubes were opened for a length of 5-6 somites at the thoracic level in Hamburger and Hamilton stage 18 chick embryos (n=150). They were reincubated in ovo. up to a total age of 17-21 days. A total of 19 embryos survived and were assigned to either the postoperative day (POD) 14-15 group (n=6) or the POD 17-18 group (n=13). Magnetic resonance imaging (MRI) and histopathologic findings of embryo heads with spinal ONTDs were compared with age-matched normal chick embryos. The chick embryos with ONTDs demonstrated definite and constant structural changes, such as downward displacement of the cerebellum to just above the foramen magnum and narrow and small cerebrospinal fluid spaces in the crowded small posterior fossa. These morphologic features were more prominent in the POD 17-18 group than in the POD 14-15 group. This is the first description of CM II with spinal ONTD in a late-stage chick embryo model with MRI and histopathological analysis. The morphological changes of the posterior fossa in this study mimic those of CM II associated with spinal ONTD in humans. This model will facilitate investigation of the pathogenesis of CM II.

Successful Treatment of Central Nervous System Involvement in Posttransplant EBV-related Lymphoproliferative Disease With Intrathecal Rituximab Therapy.

The posttransplant lymphoproliferative disease is a severe cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Central Nervous System involvement in EBV-related PTLD is rare, and there is no standard treatment recommendation. We present our patient and discuss other previously reported cases of EBV-associated PTLD with CNS involvement.

Abusive head injuries in infants: from founders to denialism and beyond.

Abusive head injuries is a major cause of severe morbidity and the main cause of mortality by head trauma ininfants. Based on published data and their own clinical and medicolegal practice, the authors review briefly the historicalroots and emergence of the concept of abusive head injuries (AHI), until the present scientific understanding ofshaken baby syndrome (SBS) and Silverman syndrome. They then discuss the present epidemic of denialism andhow this challenge to science should be seen as a stimulus to increase research and improve the accuracy ofdiagnosis and medical practice. The denial of SBS is especially damaging because it undermines the possibilities of prevention and reparation forvictims. The authors expand on AHI being part of a wider context of domestic violence and the prevention of childabuse being part of a broad and long-term endeavor to defend civilization values. Prevention of AHI is a major challenge for the future. In the fields of science and prevention of child abuse, theinput of pediatric neurosurgeons should not be underestimated.

Effects of total knee arthroplasty on balance and fall risk in elderly patients with severe gonarthrosis: An age- and sex-matched comparative study.

Falls are a severe cause of morbidity and mortality in elderly patients, and gonarthrosis causes a tendency to fall. Total knee arthroplasty (TKA) is a widely used successful surgical procedure for end-stage gonarthrosis. To investigate whether there is a difference in the frequency of falls, balance and fall risk, and clinical and radiological results in patients with end-stage gonarthrosis with and without TKA. This was a single-center, retrospective, case-control study with age- and gender-matched groups. A total of 100 patients over 60 years of age, with end-stage gonarthrosis and who met the inclusion criteria were included in the study. Fall risk was analyzed using the Berg Balance Scale (BBS), TUG tests, and the ITAKI Fall Risk Test. Knee varus angles were measured using standing long-leg radiographs, and radiological gonarthrosis grading was performed. Pain levels and quality of life were assessed using the VAS and WOMAC. Each patient's knee extensor muscle strength and range of motion were measured. WOMAC, ITAKI, TUG test, and VAS scores were significantly higher in the control group than in the TKA group. BBS scores were significantly lower in the control group. Although the number of falls was high in the control group, there was no statistically significant difference between the two groups. The results of this study showed that total knee arthroplasty provided statistically significant improvement in the clinical, radiological, and fall risk results of the patients. Although there was a decrease in the frequency of falls compared to the control group, it was statistically insignificant. In addition, in our study, it was evaluated that the most important risk factor for falling was advanced age.

Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells.

Brain metastasis is a cause of severe morbidity and mortality in cancer patients. Critical aspects of metastatic diseases, such as the complex neural microenvironment and stromal cell interaction, cannot be entirely replicated with in vitro assays; thus, animal models are critical for investigating and understanding the effects of therapeutic intervention. However, most brain tumor xenografting methods do not produce brain metastases consistently in terms of the time frame and tumor burden. Brain metastasis models generated by intracardiac injection of cancer cells can result in unintended extracranial tumor burden and lead to non-brain metastatic morbidity and mortality. Although intracranial injection of cancer cells can limit extracranial tumor formation, it has several caveats, such as the injected cells frequently form a singular tumor mass at the injection site, high leptomeningeal involvement, and damage to brain vasculature during needle penetration. This protocol describes a mouse model of brain metastasis generated by internal carotid artery injection. This method produces intracranial tumors consistently without the involvement of other organs, enabling the evaluation of therapeutic agents for brain metastasis.

Early-onset neonatal sepsis in the Paris area: a population-based surveillance study from 2019 to 2021

BackgroundEarly-onset neonatal sepsis (EOS) is a rare condition but an important cause of severe morbidity and mortality in neonates.MethodsThis is a prospective observational study in neonates born at ≥34 weeks...

Rational development of a combined mRNA vaccine against COVID-19 and influenza

As the world continues to experience the COVID-19 pandemic, seasonal influenza remain a cause of severe morbidity and mortality globally. Worse yet, coinfection with SARS-CoV-2 and influenza A virus (IAV) leads to more severe clinical outcomes. The development of a combined vaccine against both COVID-19 and influenza is thus of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we developed and characterized a novel mRNA vaccine encoding the HA antigen of influenza A (H1N1) virus, termed ARIAV. Then, ARIAV was combined with our COVID-19 mRNA vaccine ARCoV, which encodes the receptor-binding domain (RBD) of the SARS-CoV-2 S protein, to formulate the final combined vaccine, AR-CoV/IAV. Further characterization demonstrated that immunization with two doses of AR-CoV/IAV elicited robust protective antibodies as well as antigen-specific cellular immune responses against SARS-CoV-2 and IAV. More importantly, AR-CoV/IAV immunization protected mice from coinfection with IAV and the SARS-CoV-2 Alpha and Delta variants. Our results highlight the potential of the LNP-mRNA vaccine platform in preventing COVID-19 and influenza, as well as other respiratory diseases.

Liver stiffness and steatosis in preeclampsia as shown by transient elastography–a prospective cohort study

Preeclampsia is a multisystem disorder and the leading cause of severe morbidity and death in pregnancy. Liver involvement in preeclampsia ranges from elevated liver enzyme levels to hepatic infarction or rupture. Endothelial dysfunction leads to changes in blood flow and congestion and may be involved in the pathophysiology of preeclampsia. Changes in splanchnic blood flow and portal congestion can lead to altered liver stiffness. Transient elastography is a noninvasive, ultrasound-based technique that measures organ stiffness and steatosis and is therefore widely used in clinical hepatology. Previous studies reported elevated liver stiffness and liver steatosis, as measured by transient elastography, in women with preeclampsia. This study followed changes in liver stiffness and steatosis, as measured by transient elastography, from the antepartum period to 1-week postpartum among women with preeclampsia compared with healthy controls and evaluated the association between preeclampsia severity and transient elastography results. This prospective cohort study was conducted from 2017 through 2021. The study group comprised women with preeclampsia, and the control group comprised healthy pregnant women hospitalized for other reasons. All the participants underwent transient elastography either on diagnosis of preeclampsia (study group) or on hospital admission (control group) and again in the postpartum period. Liver stiffness measurements are expressed in kilopascals (kPa) in the range of 2.5 to 75 kPa, and liver steatosis isexpressed by controlled attenuation parameter in the range of 100 to 400 dB/m. The study group comprised 36 women and the control group 37. Liver stiffness scores were significantly elevated in the study when compared with the control group, both in the antepartum period (P<.001) and the postpartum period (P=.025). Liver stiffness scores decreased significantly after delivery in the study and control groups (P<.001 and P=.002, respectively). Liver steatosis scores were higher in the study group than in the control group both in the antepartum and postpartum periods (P<.001 and P<.02, respectively). In the multivariable analysis, the diagnosis of preeclampsia correlated with higher antepartum liver stiffness scores (P=.005). For the study group, postpartum liver stiffness and liver steatosis scores were increased among those with vs those without severe features of preeclampsia (P=.03 and P=.04, respectively) CONCLUSION: Reductions in liver stiffness and steatosis from the antepartum to the postpartum period were documented in both the preeclampsia and control groups. However, both these measures were higher in the preeclampsia group and correlated with preeclampsia severity. Larger studies may be able to determine whether transient elastography can predict the severity of preeclampsia or other related metabolic conditions that correlate with chronic hypertension.

Characterization of the Growth and Morphology of a BSL-2 Coccidioides posadasii Strain That Persists in the Parasitic Life Cycle at Ambient CO2.

Coccidioides is a dimorphic fungus responsible for Valley Fever and is the cause of severe morbidity and mortality in the infected population. Although there is some insight into the genes, pathways, and growth media involved in the parasitic to saprophytic growth transition, the exact determinants that govern this switch are largely unknown. In this work, we examined the growth and morphology of a Coccidioides posadasii strain (C. posadasii S/E) that efficiently produces spherules and endospores and persists in the parasitic life cycle at ambient CO2. We demonstrated that C. posadasii S/E remains virulent in an insect infection model. Surprisingly, under spherule-inducing conditions, the C. posadasii S/E culture was found to be completely hyphal. Differential interference contrast (DIC) and transmission electron microscopy (TEM) revealed unexpected cellular changes in this strain including cell wall remodeling and formation of septal pores with Woronin bodies. Our study suggests that the C. posadasii S/E strain is a useful BSL-2 model for studying mechanisms underlying the parasitic to saprophytic growth transition—a morphological switch that can impact the pathogenicity of the organism in the host.

Diagnostic Management of Pregnant Women With Suspected Pulmonary Embolism.

Pulmonary embolism (PE) is one of the most common causes of severe morbidity and mortality during pregnancy. PE diagnosis during pregnancy remains a true challenge for all physicians, as many of the symptoms and signs associated with PE are often reported during physiological pregnancy. The fear of missing a PE during pregnancy leads a low threshold of suspicion, hence to a low prevalence of confirmed PE among pregnant women with suspected PE. This means that most pregnant women with suspected PE do not have the disease. Until recently, international guidelines suggested thoracic imaging in all pregnant women with suspected PE. Two recent prospective management outcome studies based on clinical probability assessment, D-dimer measurement, venous compression ultrasonography of the lower limbs (CUS) and computed tomography pulmonary angiography (CTPA) proved the safety of such strategies, with a very low failure rate. For the first time, these studies also demonstrated that the association of a clinical prediction rule and D-dimer measurement allowed a safe exclusion of PE in a significant proportion of pregnant women, without the need for radiating imaging tests. These two prospective studies pave the way to further improvements in the diagnostic strategies. Indeed, both specific clinical prediction rules and possibly D-dimer cutoffs adapted to pregnant women could help to further reduce the proportion of patients needing thoracic imaging. As an imaging test will still ultimately be necessary in a significant proportion of women, further technical advances in CT scans protocols could reduce the radiation dose to both the fetus and the mother, an important step to reassure clinicians. Finally, educational efforts should be encouraged in the future to pass the challenge of implementing these validated diagnostic strategies in everyday clinical practice.

Cerebral vasospasm due to aneurysmal and diffuse non-aneurysmal subarachnoid hemorrhage: A single center experience

IntroductionAfter direct mortality from an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) secondary to cerebral vasospasm is a cause of severe morbidity and mortality. Distinct from perimesencephalic SAH with favorable prognosis, non-aneurysmal diffuse SAH has been observed to have a more variable outcome and requires close clinical observation as this subset of patients has a higher likelihood for developing DCI. Treatment of radiographic and clinical vasospasm is limited to only a few pharmacological agents with varying degrees of success. Several recent publications have demonstrated efficacy with using intravenous (IV) milrinone to treat cerebral vasospasm. Here, we audit the use of IV milrinone in the clinical management of vasospasm and DCI in an adult non-aneurysmal SAH population. MethodsA retrospective quality audit was conducted at a single neurosurgical center over a 1-year period (2019). Data was extracted from electronic medical records. ResultsA total of 93 adult patients were admitted for management of SAH. Twenty-four patients presented with non-aneurysmal SAH. Four patients in this group required symptomatic DCI management. All 4 patients presented with a diffuse pattern of SAH. Two of these patients presented with acute hydrocephalus requiring external ventricular drain (EVD) insertion. Most non-aneurysmal SAH patients had a good clinical outcome (92%, mRS 0–2). Two patients had a poor clinical outcome (mRS 3 and 4) at clinical follow up. These two patients initially presented with a poor clinicoradiological grading score and one patient required an urgent EVD for acute hydrocephalus. Intravenous milrinone was commenced for reduced level of consciousness (LOC) in 2/4 patients, while focal neurological deficit prompted initiation of IV therapy in the remaining 2. ConclusionPatients with diffuse non-aneurysmal SAH can develop symptomatic DCI and should be closely monitored and provided a standardized protocol for cerebral hyperdynamic therapy.

Liver stiffness in preeclampsia as shown by transient elastography

Preeclampsia (PE) is a multisystem disorder and a leading cause of severe morbidity and death in pregnancy. Liver involvement in preeclampsia ranges from elevated liver enzyme levels to hepatic infarction or rupture. Endothelial dysfunction leads to change in blood flow and congestion, and may have a role in the pathophysiology of PE. Changes in splanchnic blood flow and portal congestion can result in altered liver stiffness (LS). In previous studies, LS, measured by transient elastography, was found to be elevated in preeclamptic women.

Fatal infection with Versteria sp. in a muskrat, with implications for human health.

The Taeniidae tapeworms are a family of helminths that have a similar life cycle, with intermediate hosts developing characteristic cysts in visceral organs. We describe here a case in Pennsylvania, USA, of fatal Versteria infection in a muskrat (Ondatra zibethicus), which, to our knowledge, has not been reported to develop disease associated with infection. Postmortem examination revealed widespread tissue loss and replacement by solid-bodied cestode larvae with minimal adjacent inflammation in many visceral organs, most severe in the lungs, liver, and brain. Key morphologic features via histology included cephalic structures and short rostellar hooklets, which are characteristic for the genus. Genetic characterization confirmed the cestode as being an undescribed lineage of Versteria that has been implicated as the cause of severe morbidity and mortality in humans and nonhuman primates in North America. Considering the zoonotic significance of this pathogen, our report expands on the limited literature regarding disease caused by Versteria and emphasizes the need to identify the causative tapeworm more accurately, especially in rodent intermediate hosts given that previous reports do not have molecular confirmation of species.

40 Cattle-Related Trauma: A 5 Year Retrospective Review in An Adult Major Trauma Centre

Abstract Aim Bovine injuries are a common and significant cause of trauma, often requiring admission and operative treatment. We review all bovine related injuries over five years, both emergency and GP referrals at an adult major trauma centre in England. Method Retrospective evaluation was undertaken using keywords through radiology referrals and hospital admissions speciality databases. Demographics were collected as well as the mechanism and the situation of injury; trauma scores were calculated using: Injury Severity Score (ISS) and Probability of Survival (Ps19). Results Sixty-seven patients were identified retrospectively over 5 years, 44 emergency patients (including 23 major traumas) and 23 GP referrals. Combined (Emergency &amp; GP) mean age 52 years old. 67% male. Mean ISS 11. Most common combined mechanism of injury, kicked (n = 23). In emergency patients, trampling injuries were most common. 86% of the trampled patients were major traumas. Indirect injuries mainly involved farm gates (92%). 73% of bull-related injuries were major traumas. In emergency patients’ fractures were the most common primary injury (n = 20), upper limb followed by spine. In GP, soft tissue injuries were the most common. 70% of the emergency referrals required admission and 50% operations. Only one GP referral required an operation. Two patients had a Ps19 score &amp;lt;90. There were two mortalities. Conclusions Cattle related injuries are a significant cause of severe morbidity and mortality. They are under-reported. Patterns of injury are similar to high velocity road traffic collisions and bull-related injuries or trampling in particular, should alert the clinician to more significant trauma.

Safety bundle application on nurses’ knowledge and performance regarding management of hypertension during pregnancy and postpartum period

Background Hypertensive disorders of pregnancy (PIH) are an important cause of severe morbidity, long-term disability, and death among both mothers and their babies. Aim The aim of the study was to evaluate the safety bundle application on nurses’ knowledge and performance regarding management of hypertension during pregnancy and postpartum period. Patiehypertension, postpartum period, pregnancy, safety bundlents and methods A quasi-experimental design (pretest and posttest) was used. A purposive sample of all nurses (50 nurses) working in the obstetric hospital at Zagazig University hospitals was used in the period from January 2021 till May 2021. Two tools were used in this study: structured interviewing questionnaire that included sociodemographic data and data regarding nurses’ knowledge about management of hypertension during pregnancy and postpartum period and observational checklist to evaluate nurses’ performance about management of hypertension during pregnancy and postpartum period. Results There were highly statistical significant differences preintervention and postintervention regarding nurses’ knowledge and performance about management of hypertension during pregnancy and postpartum period. Conclusion The application of safety bundle program has a positive effect on nurses’ knowledge and practice regarding management of hypertension during pregnancy and postpartum period with a highly statistically significant difference. Recommendation Continuous educational program to improve nurses’ knowledge and performance regarding application of safety bundle in management of hypertension during pregnancy and postpartum period.

Cattle-Related Trauma: A 5-Year Retrospective Review in a Adult Major Trauma Center.

Introduction:Bovine injuries are a common and significant cause of trauma, often requiring admission and operative treatment. We review all bovine-related injuries over 5 years, both emergency and general practitioner (GP) referrals at an adult major trauma center in England.Methods:Retrospective evaluation was undertaken using the keywords through radiology referrals and hospital admissions speciality databases. By searching patient notes, demographics were collected as well as the mechanism and the situation of injury; trauma scores were calculated using: injury severity score (ISS) and probability of survival (Ps19). The results were divided into emergency patients and GP referrals.Results:Sixty-seven patients were identified retrospectively over 5 years, 44 emergency patients (including 23 major traumas), and 23 GP referrals. Combined (emergency and GP) mean age 52 years old; 67% male; and mean ISS 11. Most common combined mechanism of injury, kicked (n = 23). In emergency patients, trampling injuries were the most common. Eighty-six percent of the trampled patients were major traumas and associated with increased ISS (mean 13). Indirect injuries mainly involved farm gates (92%). Seventy-three percent of bull-related injuries were major traumas and had increased ISS scores (mean 17). Orthopaedics was the most common admitting speciality followed by cardiothoracic and neurosurgery. In emergency patients, fractures were the most common primary injury (n = 20), upper limb followed by spine. In GP, soft-tissue injuries were the most common primary injury. Seventy percent of the emergency referrals required admission and 50% operations. Fracture fixation was the most common operative procedure. Only, one GP referral required an operation. There were significant delays in GP patients presenting. Two patients had a Ps19 score <90. There were two mortalities.Conclusion:Cattle-related injuries are a significant cause of severe morbidity and mortality. They are under-reported. Patterns of injury are similar to high-velocity road traffic collisions and bull-related injuries or trampling in particular, should alert the clinician to more significant trauma. Farm gates are a frequent cause of trauma associated with cattle. GP referrals with ongoing symptoms for more than 2 weeks seeking medical advice should alert the clinician to a more serious diagnosis.

E-bike and classic bicycle-related traumatic brain injuries presenting to the emergency department

BackgroundE-bike usage is increasingly popular and concerns about e-bike-related injuries and safety have risen as more injured e-bikers attend the emergency department (ED). Traumatic brain injury (TBI) is the main...