Background: A misguided auto-reactive injury is responsible for several types of central nervous system (CNS) conditions in pediatrics. We propose that, in some of these conditions, the adaptive immune system has a common cellular immune pathogenesis, driven predominantly by T cells, despite variability on the phenotypical clinical presentation.
Methods: We have characterized the CD4+/CD8+ adaptive immune response (AIR) on pediatric patients presenting with clinical symptoms compatible with Neuroimmune Disorders (NID). Flow cytometry with deep immunophenotyping of T cells was performed on peripheral blood obtained during the acute clinical phase and compared to an age-matched cohort group (Co).
Results: We found that pediatric patients with confirmed NID, exhibit a pattern of dysregulation of CD4+ lineages associated with autoimmune processes.
Discussion: The autoimmune associated CD4+ dysregulation was associated with patients with NID, as compared to healthy controls and patients with non-autoimmune diagnoses. If we can improve our capacity for early accurate diagnosis and meaningful disease monitoring of pathogenic T cell subsets, we can both expedite disease detection and may serve as a guide to the administration of effective immunotherapeutic agents.
Background and Objective: Thrombolytic and mechanical thrombectomy therapies are proven treatment methods in patients with acute stroke. Aim is to share our experience in acute stroke therapy with colleagues.
Material and methods: In this study we evaluated the patients who underwent MT or MT + IV-tPA between 2018-2019 retrospectively. Demographic features, comorbid diseases of patients, symptom onset-to-gate and symptom gate-to-puncture durations, mRS (Modified Rankin Score) and NIHSS (National Institutes of Health Stroke Scale) score, treatment method and degree of recanalization were listed.
Results: MT was applied to 29 patients, MT + bolus IV-tPA was applied to 12 patients and MT + full dose IV-tPA was applied to 7 patients. The mean age was 66 ± 15 years, arrival mRS was 2 ± 2, arrival NIHSS score was 14 ± 5, onset-to-gate duration was 185 minutes and gate-to-puncture duration was 118 minutes.
Conclusion: The rate of recanalization, functional independence and mortality were similar to the HERMES study. It was observed a higher rate of intracranial hemorrhage in patients who received bolus or full dose IV-Tpa compared to patients who underwent MT. These results have led us to question the necessity of giving bolus or full dose IV-tPA before MT. Onset-to-gate and gate-to-puncture durations were found longer than the recommended durations. Rapid and effective management of AIS patients will provide good clinical results.
Aim: To assess the efficacy of decompressive craniectomy in patients with large basal ganglia (BG) bleed. To establish predictive criteria of mortality after surgery in patients with BG bleed.
Materials: This prospective study includes all patients of large spontaneous BG bleed operated by decompressive craniectomy without hematoma evacuation from October 2012 to September 2015. Data was collected on patient age, gender, distribution of bleed, affected hemisphere dominancy, preexisting medical conditions, admission Glasgow Coma Score (GCS), midline shift on CT or MRI Brain, hematoma volume and anisocoria, duration (hours) between the onset of stroke and operation, post-operative complications, and the duration of hospital stay. This data was correlated with one month mortality of the patients.
Results: Total number of patients were 27. Mean age was 51 years and mean GCS was 7.55(range 5-11). The mean volume of the bleed was 68.51 ml. Mortality was noted in 17 out of 27 patients (63%) in 30 days. Thirteen of the 16 patients with intraventricular extension of BG bleed had mortality. The factors that showed statistically significant correlation with one month mortality were age, GCS at admission, volume of the bleed and the intraventricular extension.
Conclusion: Large BG bleed was associated with high mortality and morbidity. Age of 50 years or more and GCS ≤ 8 at presentation were poor prognostic factors for decompressive craniectomy in patients with BG bleed. Patients with large BG bleed of volume > 60 ml and intraventricular extension had poor prognosis.
Mitochondrial and lysosomal dysfunction accounts for a large group of inherited metabolic disorders most of which are due to a dysfunctional mitochondrial respiratory chain (MRC) leading to deficient energy production and defects in phagocytosis in endosomal-lysosomal pathway respectively. MRC function depends on the coordinated expression of both nuclear (nDNA) and mitochondrial (mtDNA) genomes. Thus, mitochondrial diseases can be caused by genetic defects in either the mitochondrial or the nuclear genome, or in the cross-talk between the two. The mitochondrial DNA depletion syndromes (MDSs) are a clinically heterogeneous group of disorders with an autosomal recessive pattern of inheritance that have onset in infancy or early childhood and are characterized by a reduced number of copies of mtDNA in affected tissues and organs. In this review article, we summarized the spectrum of mtDNA depletion disorders along with minor learning of lysosomal storage diseases. This current article offers a perspective on the role of genetics in medical practice and how this role may evolve over the next several years.
The association between intracranial large vessel occlusion (LVO) and concurrent steno-occlusive lesion of an ipsilateral extracranial internal carotid artery (ICA) is considered a tandem occlusion (TO) [1]. In approximately half of TO, the first clinical manifestation are acute occlusions of the extracranial ICA associated with occlusion of the middle cerebral artery (MCA), with additional occlusion of the intracranial ICA in up to 25% of these cases.[2] This particular lesion subset is technically challenging for endovascular treatment (EVT) and is also characterized by lower success rates of intravenous thrombolysis [3], worse prognosis compared to intracranial occlusions alone, and higher rates of symptomatic intracranial hemorrhage [4]. The optimal approach regarding EVT of TO remains controversial, and reports in this regard are scarce. There are two proposed strategies according to the selection of the first lesion to be treated. The proximal approach comprises stenting of the proximal cervical ICA followed by mechanical thrombectomy (MT) of the intracranial vessel, whereas the distal approach involves MT followed by stenting of the cervical ICA [3–14].
Besides, there other clinically relevant unresolved aspects regarding the treatment of these patients, such as concomitant use of intravenous thrombolysis, the need for stenting compared to angioplasty alone, as well as the most adequate antiplatelet strategy after treatment. Accordingly, we aimed to report the procedural and clinical outcomes of a real-world experience in a comprehensive stroke center regarding EVT of anterior circulation acute ischemic stroke (AIS) associated with a TO.
Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.
Objectives: To describe a patient with facial-onset sensory-motor neuronopathy (FOSMN) that later developed Huntington’s disease (HD).
Case report: A 62-year-old woman complained of progressive dysphagia 8 years before referral. At initial evaluation, there was excessive salivation, dysphagia, and sensory-motor trigeminal impairment. Denervation was noted on the upper limbs and the tongue. Blink reflexes were abolished. Genetic study of amyotrophic lateral sclerosis (ALS)-related genes was normal. She was diagnosed with FOSMN syndrome. Her clinical state progressively worsened with corneal anesthesia, severe denutrition, right arm and axial weakness. Seven years after referral, she was unable walk and developed generalized chorea. Abnormal huntingtin gene repeat expansion confirmed the diagnosis of HD. She died 16 years after onset of dysphagia.
Conclusion: Cases with both HD and ALS have already been reported but not FOSMN and HD, to our knowledge. Some FOSMN cases have been linked to ALS-related gene mutations and HD phenocopies have been associated with C9ORF72 repeat expansions. Recently, huntingtin repeat expansions were described in the ALS population. Although a chance association cannot be excluded, data from the literature are in favor of a pathogenic relationship between FOSMN and HD in this particular case. We suggest that huntingtin gene be more systematically studied in patients with FOSMN.
Single-level Anterior Cervical Decompression and Fusion (ACDF) was initially performed using Iliac Crest Bone Graft (ICBG) [1]. Fusion rates improved when a surgical technique change, the addition of anterior plate fixation, was incorporated decades later [2,3]. Single level ACDFs with a machined allograft and plate fixation technique eventually became the industry standard as it demonstrated equivalent fusion rates with fewer complications than single level ACDFs with ICBG. This surgical technique was extended for use in patients with contiguous disk herniations. Multilevel ACDFs performed with machined allografts or interbody spacers and a two-level plate offered shorter operative times, less blood loss, better restoration of lordosis, and less immediate pain [4]. Successful multi-level ACDFs were strongly influenced by the bone graft source [5], the smoking addiction [6], and the construct stability [7]. Placement of two additional fixation screws in the central vertebral body, another improvement in the surgical technique, increased the construct strength compared to constructs with screws only placed into the end vertebral bodies [8]. Using allografts for multilevel ACDFs was a device disadvantage as they often resulted in high non-union rates [9,10].
Background: Pathological and nighttime sleep deprivations have substantial adverse effects on regulation of weight, sugar and blood pressure because of endothelial dysfunction, sympathetic nervous system stimulation, regulation and activation of systemic inflammation. Thus, this study was aimed to assess quality of sleep among patients with chronic illness and its associated factors at South Wollo Zone Public Hospitals, Northeast Ethiopia.
Methods and Materials: The study was conducted at South Wollo Zone Public Hospitals, Northeast Ethiopia from February 15 2019 till April 15 2019. Institutional based cross sectional study design was employed. All patients with chronic illness who are on follow up in South Wollo Zone Public Hospitals were sources of population. Sample size was calculated by using EPI info version 7 and the total sample size was 344. The study employed stratified random sampling technique and study participants were selected by systematic sampling. After taking ethical approval from College of Medicine and Health Sciences Ethical Approval Committee, permission from selected Hospitals and informed verbal consent from patients, the data were collected by a tool which has 3 parts: Sociodemographic data, Pittsburgh Sleep Quality Index and factors affecting sleep quality. Data were entered in to Epi data version 4.1 and exported to Statistical Package for Service Product 25 for analysis. Different data presentation tools and binary logistic regression were enrolled by considering 95% confidence level and p value of 0.05.
Result: Among the total study participants, near to one third (31.7%) of them got sleep after 30 minutes. More than one fourth of them slept for less than 7 hours. Less than half of the study participants had habitual sleep efficiency of more than 85% however 296(86%) of them did not face day time dysfunction
Conclusion and recommendations: more than one third of patients with chronic illness had poor sleep quality. One third of study participants had sleep duration of less than the recommendations(less than 7 hours). Age, educational status, residence, and perception of prognosis of disease were factors that have associations with poor sleep quality among patients with chronic illness. Health care providers who are doing in chronic illness follow up clinic should be initiated to assess and screen those patients with poor sleep quality.
Protein phosphorylation regulates several dimensions of cell fate and is substantially dysregulated in pathophysiological instances as evident spatiotemporally via intracellular localizations or compartmentalizations with discrete control by specific kinases and phosphatases. Cardiovascular disease manifests as an intricately complex entity presenting as a derangement of the cardiovascular system. Cardiac or heart failure connotes the pathophysiological state in which deficient cardiac output compromises the body burden and requirements. Protein kinases regulate several pathophysiological processes and are emerging targets for drug lead or discovery. The protein kinases are family members of the serine/threonine phosphatases. Protein kinases covalently modify proteins by attaching phosphate groups from ATP to residues of serine, threonine and/or tyrosine. Protein kinases and phosphatases are pivotal in the regulatory mechanisms in the reversible phosphorylation of diverse effectors whereby discrete signaling molecules regulate cardiac excitation and contraction. Protein phosphorylation is critical for the sustenance of cardiac functionalities. The two major contributory ingredients to progressive myocardium derangement are dysregulation of Ca2+ processes and contemporaneous elevated concentrations of reactive oxygen species, ROS. Certain cardiac abnormalities include cardiac myopathy or hypertrophy due to response in untoward haemodynamic demand with concomitant progressive heart failure. The homeostasis or equilibrium between protein kinases and phosphatases influence cardiac morphology and excitability during pathological and physiological processes of the cardiovascular system. Inasmuch as protein kinases regulate numerous dimensions of normal cellular functions, the pathophysiological dysfunctionality of protein kinase signaling pathways undergirds the molecular aspects of several cardiovascular diseases or disorders as related in this study. These have presented protein kinases as essential and potential targets for drug discovery and heart disease therapy.
A growing figure of data proposes that outcomes with Coronavirus Disease 2019 are worse in those suffering from obesity and that a significant proportion of those requiring intensive care suffers from overweight or obesity [1].
Background: End-Stage Kidney Disease and its maintenance hemodialysis treatment force patients to make several lifestyle changes to cope with this debilitating illness. These changes often trigger the onset of notable psychological distress and depressive symptoms. Furthermore, these negative psychological experiences can undermine the effectiveness of the treatment and consequently worsening the health and quality of life of patients. Objective: The study assessed the psychological well-being among hemodialysis patients in Kumasi Metropolis. Further, it explored the relationship between these psychosocial factors and demographic characteristics.Materials and Methods: 30 hemodialysis patients were recruited from two dialysis units in Kumasi, Ghana. Participants were aged 18 and above and had been on hemodialysis treatment for more than three months. The Hospital Anxiety and Depression scale (HADS) was used to assess depression and anxiety whiles the Multidimensional Scale of Perceived Social Support was used to assess perceived social support of participants. Results: The majority of respondents were males (60%), relative to females. The study revealed that 80% were severely depressed, 20% met the criteria for severe anxiety. Some participants reported moderate social support 53.3%; perceived social support being inversely correlated with both depression (r = 0.41; n = 30; p < 0.05) and anxiety (r = -0.59; n = 30; p < 0.05). Income levels were inversely correlated with depression (r = -0.41, n = 30; p < 0.05). Conclusion: Findings of the study suggest that the psychological wellbeing of hemodialysis patients is compromised. Social support appears to alleviate depression and anxiety. Implications for patient treatment are discussed.
Extant studies have labelled persons-with-addiction and the homeless as ‘invaders’ of public parks, aggressive/violent with psychiatric and medical disorders, a burden to the society, and transmitters of most deadly airborne or chronic diseases. Literature subtly discuses that such people must be chased out of the public. Yet, such studies have not concurrently analyzed from the viewpoint of urban parks users, the persons-with-addiction and the homeless people what needs to be done to improve the situation. Therefore, the study aims to explore whether problematic communities and subcultural factors make the disadvantaged resort to negative copping strategies when their legal means are blocked: how the other park users respond to the homeless drug addicts’ hardship: and the possible suggestions from all the park users. This is done with reference to social disorganization and Sub-culture theory, and through ethnographic research approach (8 months field observation) and in-depth-interviews with 27 participants. Our study found that persons-with-addiction and the homeless are not always aggressive/violent/harmful as they have been labelled. But only disadvantaged individuals who desire to emulate the ideals and ambitions of the middle class but lack resources to achieve such success. Being overwhelmed with such frustrations from their dilemmas, they consider themselves ‘double-failures’ and retreat into drug addiction and find abode in the public spaces. We therefore conclude that persons with addiction and the homeless people are not always violent and criminal persons who are to be chased out of public parks. But only disadvantaged individuals who need help for choosing a negative coping strategy.
Background: In France, from 30% to 35% of children suffer from multiple food allergies (MFA). The gold standard to diagnosis a food allergy is the oral food challenge (OFC) which is conducted in a hospital setting due to risk of anaphylaxis. The aim of this study was to evaluate an algorithm to predict OFCs at low risk of anaphylaxis that could safely be performed in an office-based setting. Methods: Children with MFA and at least one open OFC reactive or non-reactive to other allergens were included. The algorithm was based on multiple clinical and biological parameters related to food allergens, and designed mainly to predict “low-risk” OFCs i.e., practicable in an office-based setting. The algorithm was secondarily tested in a validation cohort. Results: Ninety-one children (median age 9 years) were included; 94% had at least one allergic comorbidity with an average of three OFCs per child. Of the 261 OFCs analyzed, most (192/261, 74%) were non-reactive. The algorithm failed to correctly predict 32 OFCs with a potentially detrimental consequence but among these only three children had severe symptoms. One hundred eighty-four of the 212 “low-risk” OFCs, (88%) were correctly predicted with a high positive predictive value (87%) and low negative predictive value (44%). These results were confirmed with a validation cohort giving a specificity of 98% and negative predictive value of 100%. Conclusion: This study suggests that the algorithm we present here can predict “low-risk” OFCs in children with MFA which could be safely conducted in an office-based setting. Our results must be confirmed with an algorithm-based machine-learning approach.
Background: Latin America has always had high maternal and infant mortality rates. However, the prevalence of asthma in pregnant patients and their outcomes are unknown. We aimed at answering those questions in a developing country’s maternity hospital. Methods: Since January 2011, a cohort of 591 pregnant asthma patients was prospectively recruited for 60 consecutive months. Patients were followed up by a multidisciplinary team until delivery. They were divided into two groups: one of 186 smokers or morbidly obese patients and another of 405 nonobese nonsmokers. Outcomes of mothers and their babies were documented.Results: Out of 57,031 deliveries, the overall estimated prevalence of 591 asthmatic pregnant patients was 1.03%. When adjusted for age standardized prevalence, it turned to 9.2%.With 28 maternal deaths (49 per 100,000 live births). None of these women had asthma. There were also 413 deaths among newborns (7.24/1000 live births). One occurred in the smoker/obese group (5.37/1000 live births) and two in the nonsmoker nonobese group (4.84/1000 live births). The prevalence of asthma during pregnancy seemed lower than in some affluent societies. Overall maternal mortality rates were similar to national figures; however, data on mothers’ mortality with asthma were unexpectedly absent.Conclusion: A multidisciplinary approach and the use of a low-cost inhaled steroid seemed to be the reasons for this. However, infant mortality rate remained high, which could be related to the risk of asthma itself. We believe there’s a worldwide need for agreements on a standardized approach for asthma’s epidemiological surveys, in order to make them comparable
Objective: To investigate the occurrence of depressive and anxiety disorders in patients remitted for endovascular treatment of renal artery stenosis (RAS), and whether symptoms of depression and anxiety can be reduced after the treatment of RAS with percutaneous transluminal renal angioplasty (PTRA).Methods Patients: Selected for renal angiography with pressure measurement in the renal arteries due to suspected RAS were invited to participate in the study. 37 patients agreed to answer a questionnaire. Eighteen patients also agreed to a clinical psychiatric examination including the International Neuropsychiatric Interview (M.I.N.I. 6.0) to be diagnosed according to the DSM-IV. Results: Twenty-one of the 37 patients completing the questionnaire were found to have a pressure gradient of ≥ 10 mmHg at angiography, indicating significant stenosis. Ten of the 18 examined patients met the criteria for current DSM-IV anxiety diagnosis and two patients had a current depression. Three of the 18 examined patients had previously made a suicide attempt. Conclusion: The results of this study suggest that patients with suspected RAS have a high psychiatric comorbidity, as 56% of the patients undergoing psychiatric examination met the DSM-IV criteria for a current anxiety disorder.
Repressive regulation of potassium channel genes by Polycomb group (PcG) proteins contributes to PcG protein-mediated neuroprotection against neuronal ischemic injury, as seen in an ischemic stroke. Here we asked the question whether Trithorax group (TrxG) proteins, the antagonistic partners of PcG proteins (i.e, epigenetic activators targeting the same genes) may also regulate potassium channels. Results of patch-clamp studies on cultured neuronal cells showed that inhibition of TrxG protein MLL-1 led to an increase in potassium channel activity, an unexpected effect for a presumed gene activator. In contrast, decreased sodium currents were observed with MLL-1 inhibition. Increased or decreased levels of potassium channel protein Kv2.1 or sodium channel protein Nav1.2, respectively, were seen with MLL-1 inhibition, as determined by immunocytochemistry. These results, for the first time, demonstrate an involvement of TrxG protein MLL-1 in regulating neuronal ion channels, potentially repressing potassium channel genes.
Beatriz Bonaga*, Elena Ruiz-Escribano Taravilla, Carmen Carrilero-López, María Dolores Castillo-Lag, Leanne M Boehm, Ángela Prado Mira, María Joaquina Piqueras Diaz and E Wesley Ely
Background: Delirium is an acute syndrome of organ dysfunction with long-term consequences which commonly occurs in the Intensive Care Unit (ICU). The incidence of delirium ranges from 30% - 50% in low severity ICU patients and up to 80% in mechanically ventilated patients. This condition is frequently under-recognized and daily routine screening is a key strategy to early intervention. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) are the most recommended assessment tools for detecting delirium in the critical ill patient.
Objective: The main objective of this study is to educate ICU staff about delirium. In addition, nurses were trained to use the CAM-ICU as a standard screening tool. The intervention was evaluated through a survey aimed at ICU staff.
Methods: An educational intervention was started in 2014 in our ICU. An educational package for ICU staff consisted of a didactic brochure and explanatory videos. One-on-one teaching, case based scenarios and didactic teaching were strategies used in the implementation process. The entire intervention was evaluated by means of a survey directed to the professionals.
Results: The structure of the didactic brochure was simple in order to have an easy understanding of the CAM-ICU tool. We also created 10-minute videos. According to the results of the satisfaction survey (N=62), disorganized thinking was the most difficult feature of CAM-ICU to interpret. When in doubt, consultation between co-workers was the primary resource selected by unit staff.
Conclusion: This initiative achieved the objective of training health care professionals in the application of the CAM-ICU tool with a good level of satisfaction from them. Therefore, ICU staff consider delirium management in the broader picture of critically ill patient care as a major activity of daily practice.
Background: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak severely hit Northeastern France from March to May 2020. The massive arrival of SARS-CoV-2 positive patients in the intensive care units (ICU) raised the question of how immunocompromised patients would be affected. Therefore, we analyzed the clinical, biological and radiological features of 24 immunocompromised ICU patients with severe SAR-CoV-2 infection.
Results: The mortality rate was significantly higher for immunocompromised patients compared with other patients (41.7% versus 27.3%, respectively, p = 0.021). Mortality occurred in the first 2 weeks of intensive care, highlighting the possible interest in prolonged full-code managnement of these patients. Finally, patients with lymphoid malignancies appeared to be particularly affected, mostly with monoclonal gamma-pathology.
Conclusion: Mortality rate of SARS-CoV-2 acute respiratory syndrome in immuno-compromised patient is high. No treatment was associated with survival improvement. Prolonged full-code management is required for these patients.
Familial dysautonomia is a rare autosomal recessive neurodegenerative disease affecting cells of the autonomic nervous system. Patients with this disease are insensitive to pain but their autonomic nervous system is still activated with noxious stimuli. This report details a case of a patient with familial dysautonomia who underwent right ankle open reduction and internal fixation for a bimalleolar right ankle fracture. The patients preoperative and intraoperative course were uneventful but shortly after handoff to the intensive care unit, the patient experienced an autonomic crisis. Management of these patients is complex, requiring maintenance of physiologic homeostasis as well as preventing hemodynamic instability caused by noxious stimuli. Any deviations from baseline may cause an autonomic crisis, as happened in our patient. Herein, we detail the perioperative management of a patient with familial dysautonomia in further detail.
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