scholarly journals Timely Recognition and Early Multi-Step Antinflammatory Therapy May Prevent ICU Admission of Patients With MIS-C: Proposal for a Severity Score

2021 ◽  
Vol 9 ◽  
Author(s):  
Giacomo Brisca ◽  
Alessandro Consolaro ◽  
Roberta Caorsi ◽  
Daniela Pirlo ◽  
Giulia Tuo ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Therapeutic Response ◽  
Invasive Mechanical Ventilation ◽  
Clinical Manifestations ◽  
Treatment Protocol ◽  
Therapeutic Interventions ◽  
Inotropic Drugs ◽  
Function Impairment ◽  
Treatment Escalation ◽  
Inflammatory Syndrome

In this observational study, we report the clinical, therapeutics and outcome features of 23 patients with multisystem inflammatory syndrome (MIS-C) who have been treated in Gaslini Children Hospital (Genoa, Italy) with a multistep antinflammatory treatment protocol, based on disease severity at admission. Patients were initially assigned to four severity classes on admission and treated accordingly. The therapeutic options ranged from IV immunoglobulin alone to a combination of IVIG plus pulses of methylprednisolone plus anakinra for patients with marked cardiac function impairment or signs of macrophage activation syndrome, with rapid treatment escalation in case of inadequate therapeutic response. With the application of this therapeutic strategy, no patient required admission to Intensive Care Unit (ICU) or invasive mechanical ventilation, and no inotropic drugs administration was required. Early aggressive treatment of MIS-C, with therapeutic interventions modulated based on the severity of clinical manifestations may help to prevent the progression of the inflammatory process and to avoid the need of admission to the ICU. A timely intervention with anti-IL-1 blockers can play a pivotal role in very severe patients that are at risk to have an incomplete response to immunoglobulins and steroids.

scholarly journals COVID-19-associated multisystem inflammatory syndrome in children: Experiences of three centres in Turkey

2021 ◽  
Author(s):  
Hakan Salman ◽  
Nagehan Aslan ◽  
Mustafa Akçam ◽  
Müjgan Arslan ◽  
Emine Akkuzu ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Intravenous Immunoglobulin ◽  
Invasive Mechanical Ventilation ◽  
Clinical Manifestations ◽  
Neurological Involvement ◽  
Neurological Signs ◽  
Control And Prevention ◽  
Fatal Course ◽  
Paediatric Practice ◽  
Inflammatory Syndrome

ABSTRACT Background The pathogenesis and clinical manifestations of the multisystem inflammatory syndrome in children (MIS-C) has not yet been fully elucidated and there is no clear consensus on its treatment yet. Objectives To evaluate our patients diagnosed with MIS-C and present them to the literature in order to contribute to the better understanding of this new disease, which entered paediatric practice with the SARS-CoV-2 peak. Methods In this study, 17 MIS-C cases diagnosed according to the Centers for Disease Control and Prevention criteria were included. Results Of the patients, 7 (41.2%) had a comorbidity. Gastrointestinal system involvement was the most prominent in the patients (70.6%). Laparotomy was performed in 3 patients due to acute abdomen. Two patients had neurological involvement. Of the patients, 15 (88.2%) received intravenous immunoglobulin and 13 (76.5%) received both intravenous immunoglobulin and methylprednisolone. Two patients received invasive mechanical ventilation and 4 patients received high flow rate nasal cannula oxygen therapy. One of our patients who needed invasive mechanical ventilation and high vasoactive-inotrope support died despite all supportive treatments including plasmapheresis and extracorporeal membrane oxygenation. Conclusions MIS-C picture can have a fatal course and may present with severe gastrointestinal and neurological signs. Unnecessary laparotomy should be avoided.

scholarly journals Pediatric leukemia susceptibility disorders: manifestations and management

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 242-250 ◽  
Author(s):  
Lisa J. McReynolds ◽  
Sharon A. Savage
Keyword(s):  
Early Onset ◽  
Ribosome Biogenesis ◽  
De Novo ◽  
Disease Risk ◽  
Bone Marrow Failure ◽  
Clinical Manifestations ◽  
Cancer Surveillance ◽  
Therapeutic Interventions ◽  
Pediatric Leukemia ◽  
Inherited Susceptibility

Abstract The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or early-onset myelodysplastic syndrome (MDS) and some with no obvious medical problems until they develop leukemia. Leukemia susceptibility syndromes occur as a result of autosomal dominant, autosomal recessive, or X-linked recessive inheritance, or de novo occurrence, of germline pathogenic variants in DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, and other critical cellular processes. Children and adults with cytopenias, MDS, dysmorphic features, notable infectious histories, immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity to radiation or chemotherapy, or acute leukemia with a family history of early-onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly evaluated for a leukemia susceptibility syndrome. Genetic testing and other diagnostic modalities have improved our ability to identify these patients and to counsel them and their family members for subsequent disease risk, cancer surveillance, and therapeutic interventions. Herein, the leukemia susceptibility syndromes are divided into 3 groups: (1) those associated with an underlying inherited bone marrow failure syndrome, (2) disorders in which MDS precedes leukemia development, and (3) those with a risk primarily of leukemia. Although children are the focus of this review, it is important for clinicians to recognize that inherited susceptibility to cancer can present at any age, even in older adults; genetic counseling is essential and prompt referral to experts in each syndrome is strongly recommended.

scholarly journals Amorphous Ropinirole-Loaded Mucoadhesive Buccal Film: A Potential Patient-Friendly Tool to Improve Drug Pharmacokinetic Profile and Effectiveness

2020 ◽  
Vol 10 (4) ◽  
pp. 242
Author(s):  
Giulia Di Prima ◽  
Giuseppina Campisi ◽  
Viviana De Caro
Keyword(s):  
Buccal Mucosa ◽  
Therapeutic Strategy ◽  
Therapeutic Response ◽  
Ex Vivo ◽  
Hepatic Metabolism ◽  
Pharmacokinetic Profile ◽  
Promising Candidate ◽  
Steady State Condition ◽  
Drug Pharmacokinetic ◽  
Drug Flux

Nowadays the therapeutic strategies to manage Parkinson’s Disease are merely symptomatic and consist of administering L-DOPA and/or dopamine receptor agonists. Among these, Ropinirole (ROP) is a widely orally-administered molecule, although it is extensively susceptible to hepatic metabolism. Since literature reports the buccal mucosa as a potentially useful route to ROP administration, the development of novel, effective, and comfortable oromucosal formulations should prove desirable in order to both enhance the therapeutic efficacy of the drug and allow a personalized therapeutic strategy able to meet the patient’s needs. The results of the proposed ROP film as a new dosage form show that it is flexible; uniform; and characterized by suitable surface pH; good mucoadhesiveness; low swelling degree; and fast, complete drug release. Moreover, after ex vivo evaluation on a film having an area of 0.282 cm2 and dose of 2.29 mg, the results of drug flux through the buccal mucosa are closely comparable to the amount of ROP that reaches the bloodstream at the steady-state condition after ROP-PR 4 mg oral administration, calculated according to the literature (0.237 mg/cm2·h−1 vs. 0.243 mg/h, respectively). Moreover, drug flux and ROP dose could be accurately modulated time-by-time depending on the patient’s need, by varying the administered disk area. In addition, the proposed ROP film displays no lag time, producing an immediate drug input in the bloodstream, which could result in a prompt therapeutic response. These findings make ROP film a potentially comfortable and patient-friendly formulation, and a promising candidate for further clinical trials.

scholarly journals Novel therapeutic interventions towards improved management of septic arthritis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jian Wang ◽  
Liucai Wang
Keyword(s):  
Antibiotic Therapy ◽  
Septic Arthritis ◽  
Clinical Success ◽  
Treatment Protocol ◽  
Current Treatment ◽  
Therapeutic Interventions ◽  
Medical Emergency ◽  
Success Rates ◽  
Joint Infections ◽  
Novel Therapeutic

AbstractSeptic arthritis (SA) represents a medical emergency that needs immediate diagnosis and urgent treatment. Despite aggressive treatment and rapid diagnosis of the causative agent, the mortality and lifelong disability, associated with septic arthritis remain high as close to 11%. Moreover, with the rise in drug resistance, the rates of failure of conventional antibiotic therapy have also increased. Among the etiological agents frequently isolated from cases of septic arthritis, Staphylococcus aureus emerges as a dominating pathogen, and to worsen, the rise in methicillin-resistant S. aureus (MRSA) isolates in bone and joint infections is worrisome. MRSA associated cases of septic arthritis exhibit higher mortality, longer hospital stay, and higher treatment failure with poorer clinical outcomes as compared to cases caused by the sensitive strain i.e methicillin-sensitive S. aureus (MSSA).In addition to this, equal or even greater damage is imposed by the exacerbated immune response mounted by the patient’s body in a futile attempt to eradicate the bacteria. The antibiotic therapy may not be sufficient enough to control the progression of damage to the joint involved thus, adding to higher mortality and disability rates despite the prompt and timely start of treatment. This situation implies that efforts and focus towards studying/understanding new strategies for improved management of sepsis arthritis is prudent and worth exploring.The review article aims to give a complete insight into the new therapeutic approaches studied by workers lately in this field. To the best of our knowledge studies highlighting the novel therapeutic strategies against septic arthritis are limited in the literature, although articles on pathogenic mechanism and choice of antibiotics for therapy, current treatment algorithms followed have been discussed by workers in the past. The present study presents and discusses the new alternative approaches, their mechanism of action, proof of concept, and work done so far towards their clinical success. This will surely help to enlighten the researchers with comprehensive knowledge of the new interventions that can be used as an adjunct therapy along with conventional treatment protocol for improved success rates.

scholarly journals Hypophosphatasia: A Unique Disorder of Bone Mineralization

2021 ◽  
Vol 22 (9) ◽  
pp. 4303
Author(s):  
Juan Miguel Villa-Suárez ◽  
Cristina García-Fontana ◽  
Francisco Andújar-Vera ◽  
Sheila González-Salvatierra ◽  
Tomás de Haro-Muñoz ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Genetic Disease ◽  
Therapeutic Strategy ◽  
Pediatric Patients ◽  
Bone Mineralization ◽  
Clinical Manifestations ◽  
Allelic Heterogeneity ◽  
Specific Enzyme ◽  
Inorganic Pyrophosphate ◽  
Enzyme Replacement

Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5′-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.

scholarly journals SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment

2021 ◽  
Author(s):  
Nahed Abdel-Haq ◽  
Basim I. Asmar ◽  
Maria P. Deza Leon ◽  
Eric J. McGrath ◽  
Harbir S. Arora ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Infliximab Treatment ◽  
Inflammatory Syndrome

scholarly journals Animal models of bronchopulmonary dysplasia. The term mouse models

2014 ◽  
Vol 307 (12) ◽  
pp. L936-L947 ◽  
Author(s):  
Jessica Berger ◽  
Vineet Bhandari
Keyword(s):  
Animal Models ◽  
Lung Injury ◽  
Mouse Models ◽  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Invasive Mechanical Ventilation ◽  
Therapeutic Interventions ◽  
Contributing Factors ◽  
Short Term ◽  
Injury Models

The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante- and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.

scholarly journals Targeting Mitochondria as Therapeutic Strategy for Metabolic Disorders

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Daniela Sorriento ◽  
Antonietta Valeria Pascale ◽  
Rosa Finelli ◽  
Anna Lisa Carillo ◽  
Roberto Annunziata ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mitochondrial Dysfunction ◽  
Small Molecules ◽  
Metabolic Disorders ◽  
Therapeutic Strategy ◽  
Cell Metabolism ◽  
Therapeutic Interventions ◽  
Mtdna Mutations ◽  
Pathological Conditions ◽  
Mitochondria Targeting

Mitochondria are critical regulator of cell metabolism; thus, mitochondrial dysfunction is associated with many metabolic disorders. Defects in oxidative phosphorylation, ROS production, or mtDNA mutations are the main causes of mitochondrial dysfunction in many pathological conditions such as IR/diabetes, metabolic syndrome, cardiovascular diseases, and cancer. Thus, targeting mitochondria has been proposed as therapeutic approach for these conditions, leading to the development of small molecules to be tested in the clinical scenario. Here we discuss therapeutic interventions to treat mitochondrial dysfunction associated with two major metabolic disorders, metabolic syndrome, and cancer. Finally, novel mechanisms of regulation of mitochondrial function are discussed, which open new scenarios for mitochondria targeting.

ATP8B1 deficiency: general background, clinical manifestations and possible therapeutic interventions

2009 ◽  
pp. 235-242
Author(s):  
J. M. Stapelbroek ◽  
L. M. Van der Velden ◽  
S. F. J. van de Graaf ◽  
L. W. J. Klomp ◽  
R. H. J. Houwen
Keyword(s):  
Clinical Manifestations ◽  
Therapeutic Interventions
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