scholarly journals Tocilizumab for the Treatment of Mevalonate Kinase Deficiency

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Nadia K. Rafiq ◽  
Helen Lachmann ◽  
Frodi Joensen ◽  
Troels Herlin ◽  
Paul A. Brogan
Keyword(s):  
Autoinflammatory Disease ◽  
Energy Levels ◽  
Poor Quality ◽  
Mevalonate Kinase Deficiency ◽  
Mevalonate Kinase ◽  
Recessive Mutations ◽  
Limited Experience ◽  
Life Threatening ◽  
Important Addition

Mevalonate kinase deficiency (MKD) is a severe autoinflammatory disease caused by recessive mutations in MVK resulting in reduced function of the enzyme mevalonate kinase, involved in the cholesterol/isoprenoid pathway. MKD presents with periodic episodes of severe systemic inflammation, poor quality of life, and life-threatening sequelae if inadequately treated. We report the case of a 12-year-old girl with MKD and severe autoinflammation that was resistant to IL-1 and TNF-αblockade. In view of this, she commenced intravenous tocilizumab (8 mg/kg every 2 weeks), a humanised monoclonal antibody targeting the IL-6 receptor (IL-6R) that binds to membrane and soluble IL-6R, inhibiting IL-6-mediated signaling. She reported immediate cessation of fever and marked improvement in her energy levels following the first infusion; after the fifth dose, she was in complete clinical and serological remission, now sustained for 24 months. This is one of the first reported cases of a child with MKD treated successfully with tocilizumab and adds to the very limited experience of this treatment for MKD. IL-6 blockade could therefore be an important addition to the armamentarium for the treatment of this rare monogenic autoinflammatory disease.

Association Between Elevated Hemolysis at Diagnosis and Early Mortality and Risk of Thrombosis In Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients with Cytopenia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4241-4241 ◽  
Author(s):  
Jin Seok Kim ◽  
Jong Wook Lee ◽  
Sung-Soo Yoon ◽  
Je-Hwan Lee ◽  
Deog-Yeon Jo ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Risk Factor ◽  
Abdominal Pain ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Poor Quality ◽  
Severe Fatigue ◽  
Life Threatening

Abstract Abstract 4241 Introduction: PNH is a rare, progressive and life threatening disease driven by chronic hemolysis leading to thrombosis, renal impairment, pain, severe fatigue, poor quality of life and premature death. Thrombosis is the leading cause of death (accounting for 40–67% of PNH-related deaths) and was recently identified as a significant risk factor for mortality in Asian PNH patients. Abdominal pain is a common and distressing symptom in PNH and has also been found to be risk factor for thrombosis and mortality in PNH patients. In PNH patients with concomitant aplasia/cytopenias (PNH-cytopenia), the symptoms associated with hemolytic PNH (i.e., severe fatigue and anemia) may be attributed to a hypocellular marrow, potentially masking the life threatening risk of hemolysis-mediated thrombosis and abdominal pain. Here we evaluate the correlation of clinical risk factors with hemolytic symptoms in cytopenic PNH patients. Methods: We retrospectively analyzed medical charts of 286 PNH patients from the National Data Registry in South Korea to identify aplastic PNH patients with evidence of hemolytic symptoms at the time of diagnosis. We defined PNH-cytopenia patients with evidence of at least 2 of the following hematological values at diagnosis: Hgb <10 g/dL; ANC <1.5×109/L; thrombocytopenia <100×109/L. Hemolysis was defined as LDH °Ã1.5 fold above the upper limit of normal (ULN). Results: The median patient age was 37 years (range: 8 to 88 years) and median PNH duration was 7.8 years. At diagnosis, median PNH granulocyte clone was 49% and LDH was 3.9-fold above ULN. Median platelet count was 99×109/L and median ANC was 1.2×109/L, 21% with ANC <1.0×109/L. PNH-cytopenia was identified at diagnosis in 42% of PNH patients. PNH-cytopenic patients experienced a similar prevalence of hemolytic symptoms and mortality compared to PNH patients with no evidence of cytopenia (PNH) (see table below). Thrombosis was equally prevalent in PNH-cytopenia compared to PNH (12% vs18%; P=0.175). Abdominal pain was equally prevalent in PNH-cytopenia and PNH (52% vs 42%; P=0.112) and there was similar mortality between the 2 groups (13% vs 11%; P=0.631). There was a significantly higher prevalence of mortality (14% vs 4%; p=0.048), thrombosis (22% vs 4%; p=0.003) and abdominal pain (53% vs 32%; p=0.007) in patients with elevated hemolysis (°Ã LDH 1.5 above ULN) compared to patients without hemolysis. We found that 69% of PNH-cytopenia patients demonstrated elevated hemolysis at diagnosis. Thrombosis was identified in 17% of PNH-cytopenia patients with elevated hemolysis compared to 3% with no evidence of elevated LDH (p=0.051); abdominal pain (59% vs 32%; p= 0.012) and death (16% vs 3%; p=0.070) were higher in PNH-cytopenia patients with hemolysis compared to PNH-cytopenia patients without hemolysis. CONCULSION: These data demonstrate that the presence of hemolysis at diagnosis is associated with of life-threatening thrombosis, poor quality of life, and mortality in PNH patients. Despite the evidence of hypoplasia, PNH-cytopenia patients with hemolysis demonstrate a higher risk of life-threatening thrombosis, pain, and mortality. These data indicate that hemolysis is a potential risk factor for life- threatening complications independent of the presence of cytopenia in patients with PNH. Treatment for PNH patients with cytopenias should focus on both controlling hemolysis as well as improving hypoplasia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hypoglycaemia in Type 2 Diabetes – Clinical Consequences and Impact on Treatment

2010 ◽  
Vol 06 ◽  
pp. 29
Author(s):  
Chantal Mathieu ◽  
Claudia Filozof ◽  
Anthony H Barnett ◽  
◽  
◽  
...  
Keyword(s):  
Quality Of Life ◽  
Poor Quality ◽  
Careful Monitoring ◽  
Patients With Diabetes ◽  
Clinical Consequences ◽  
Life Threatening ◽  
Treatment Of Diabetes ◽  
Impact On Treatment

For patients with diabetes, hypoglycaemia can present a number of risks ranging from mild to life-threatening in severity. Frequently occurring hypoglycaemia is associated with increased morbidity and mortality. Recent studies have found associations between intensive glycaemia treatment and an increased incidence of hypoglycaemia, prompting much discussion concerning the clinical significance of hypoglycaemia in the treatment of diabetes, especially considering that many hypoglycaemic episodes are subclinical and unrecognised. Hypoglycaemia has also been linked to an increased probability of developing dementia and, not surprisingly, poor quality of life as well. It may be helpful to try to prevent hypoglycaemic episodes through careful monitoring of patients with risk factors that predispose them to hypoglycaemia, while also selecting therapies that can minimise the incidence of hypoglycaemic episodes

scholarly journals The Risk Assessment of Adverse Events of Nursing Activities as the Element of Quality Management in Healhcare

2015 ◽  
Vol 6 (1) ◽  
pp. 79-86
Author(s):  
Malgorzata Z. Wiśniewska ◽  
Piotr Grudowski ◽  
Emila Konieczyńska
Keyword(s):  
Risk Assessment ◽  
Adverse Events ◽  
District Hospital ◽  
First Aid ◽  
Poor Quality ◽  
Pareto Analysis ◽  
Management Commitment ◽  
Life Threatening ◽  
Staff Supervision

Abstract The purpose of the paper is to present MedCARVER+Shock method and Pareto analysis and its usability for the risk assessment of adverse events of nursing activities. 888 activities carried out by all 190 nurses working at the District Hospital X located in Poland were taken into account. During the research the qualitative approach was used. As the result sixteen groups of nursing activities causing the highest risk of adverse events were selected. Special attention required in: admission of a patient to the ward, sterilization, verbal communication with the patient, using of intravenous cannulas, needles, syringes, devices for transfusion of infusion liquids, servicing of hospital rooms, first aid in life-threatening situations, using medical devices and equipment. Ten basic causes of the risk of adverse events were identified, among others: lack of trainings, of modern equipment, of staff, failure to comply with procedures, lack of staff supervision, poor quality of ancillary materials, lack of management commitment. Finally MedCARVER+Shock method and Pareto analysis usability has been confirmed but it appeared that it is time-consuming and requires support from skilled professionals. Several suggestions have been put forward to improve the utility of MedCARVER+Shock.

scholarly journals The Incidence of Depression and the Decrease of Quality of Life in Patients with Moderate-Severe Inflammatory Acne

2019 ◽  
Vol 2 (4) ◽  
pp. 143-149
Author(s):  
C.A. Verdeja-Robles ◽  
C.E. Velazquez-De la Rosa ◽  
A. Gutiérrez-Morgas
Keyword(s):  
Quality Of Life ◽  
Skin Diseases ◽  
Acne Vulgaris ◽  
Poor Quality ◽  
Cross Sectional ◽  
Severe Acne ◽  
Long Time ◽  
Life Threatening ◽  
The Impact

Abstract Objective: to know the prevalence of depression in patients with moderate-severe acne vulgaris. Hypothesis: the incidence of depression increases in patients with moderate-severe acne vulgaris and will therefore decrease the quality of life. Background: acne is a very frequent dermatosis in the outpatient clinic, it is not considered a life-threatening disease. It has been associated with negative emotional status. Also, suffering from it for a long time has been associated with depression, anxiety and frustration. The complications of acne in the psychosocial aspect are related to academic or vocational performance, self-esteem and adolescents’ quality of life. Materials and Methods: the type of study was retrospective cross-sectional descriptive observational study. The sampling was carried out at the facilities of the Popular Autonomous University of the State of Puebla, taking into account any person within the institutional organisation within the range of 12-20 years of age, with a total of 50 participants. The Hamilton assessment scale of depression and the Cardiff Acne disability index were applied to all patients with dermatological diagnosis of moderate-severe vulgar acne in a period between February-October 2019. Results: a total of 50patients were analysed, of which 28 were women aged 12 to 20 years and 22 men (28 women and 13 men) and severe acne in 9 patients, all over 17 years of age and male. According to the degree of depression, 28% (n = 14) of the patients were obtained without some degree of depression; 60% (n = 30) with minor depression; 12% (n = 6) with moderate depression. Regarding the quality of life: 40% (n = 20) of the patients showed good quality of life, 46% (n = 23) regular quality of life and 14% (n = 7) showed poor quality of life. Conclusion: orderly study of the psychic impact of acne and other skin diseases on people suffering them is recent and is carried out through questionnaires that try to measure the impact the diseases have on the patients’ quality of life.

Mevalonate kinase deficiency, a metabolic autoinflammatory disease

2013 ◽  
Vol 147 (3) ◽  
pp. 197-206 ◽  
Author(s):  
Robert van der Burgh ◽  
Nienke M. ter Haar ◽  
Marianne L. Boes ◽  
Joost Frenkel
Keyword(s):  
Autoinflammatory Disease ◽  
Mevalonate Kinase Deficiency ◽  
Mevalonate Kinase

scholarly journals Ossification of the Anterior Longitudinal Ligament with Dysphagia as the First Symptom: Rehabilitation of Two Cases

2021 ◽  
Vol 11 (16) ◽  
pp. 7300
Author(s):  
Norihiro Nishida ◽  
Hiroyoshi Ogasa ◽  
Kazushige Seki ◽  
Tomohiro Kato ◽  
Yasuaki Imajo ◽  
...  
Keyword(s):  
Treatment Options ◽  
Poor Quality ◽  
Timing Of Surgery ◽  
Screening Tests ◽  
Posterior Fixation ◽  
Anterior Longitudinal Ligament ◽  
Posterior Decompression ◽  
Pharyngeal Cavity ◽  
Life Threatening

Dysphagia is associated with poor quality of life, and pneumonia due to aspiration is life-threatening. Cervical ossification of the anterior longitudinal ligament (C-OALL) is one of the causes of dysphagia, and we report two cases in which dysphagia improved after surgery. Case 1: A 76-year-old man had C-OALL of greater than 16 mm and dysphagia and developed myelopathy. A fall resulted in upper and lower limb insufficiency paralysis, and posterior decompression fixation was performed. Pressure on the pharynx by C-OALL remained, but dysphagia improved. Improvement in this case was considered to be due to the loss of intervertebral mobility. Case 2: A 62-year-old man developed dysphagia 6 years ago. It gradually exacerbated, and the C-OALL increased. Laryngeal fiberscope and swallowing angiography revealed that the pharyngeal cavity was compressed and narrowed anteriorly due to ossification. Resection of the ossification was performed, and the patient’s symptoms improved. Direct decompression was successful in this case. Several evaluation methods for dysphagia have been reported, including screening tests, endoscopy, contrast studies, and radiological evaluation. In case 1, extensive ossification was improved by posterior fixation, albeit incidentally, whereas in case 2, a patient with extensive ossification exhibited symptoms. It is necessary to examine the cervical mobility, extent and morphology of ossification, and timing of surgery stenosis to determine the risk factors and treatment options, including rehabilitation.

scholarly journals Repositioning of Tak-475 In Mevalonate Kinase Disease: Translating Theory Into Practice

2018 ◽  
Vol 25 (24) ◽  
pp. 2783-2796 ◽  
Author(s):  
Annalisa Marcuzzi ◽  
Claudia Loganes ◽  
Claudio Celeghini ◽  
Giulio Kleiner
Keyword(s):  
Mevalonate Pathway ◽  
Clinical Symptoms ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Mevalonate Kinase Deficiency ◽  
Mevalonate Kinase ◽  
Similar Action ◽  
Cellular Models ◽  
Inflammatory Stimuli

Background: Mevalonate Kinase Deficiency (MKD, OMIM #610377) is a rare autosomal recessive metabolic and inflammatory disease. In MKD, defective function of the enzyme mevalonate kinase, due to a mutation in the MVK gene, leads to the shortage of mevalonate- derived intermediates, which results in unbalanced prenylation of proteins and altered metabolism of sterols. These defects lead to a complex multisystem inflammatory and metabolic syndrome. <p> Objective: Although biologic therapies aimed at blocking the inflammatory cytokine interleukin- 1 can significantly reduce inflammation, they cannot completely control the clinical symptoms that affect the nervous system. For this reason, MKD can still be considered an orphan drug disease. The availability of MKD models reproducing the MKD-systematic inflammation, is crucial to improve the knowledge on its pathogenesis, which is still unknown. New therapies are also required in order to improve pateints’ conditions and their quality of life. <p> Methods: MKD-cellular models can be obtained by biochemical inhibition of mevalonatederived isoprenoids. Of note, these cells present an exaggerated response to inflammatory stimuli that can be reduced by treatment with zaragozic acid, an inhibitor of squalene synthase, thus increasing the availability of isoprenoids intermediates upstream the enzymatic block. <p> Results: A similar action might be obtained by lapaquistat acetate (TAK-475, Takeda), a drug that underwent extensive clinical trials as a cholesterol lowering agent 10 years ago, with a good safety profile. <p> Conclusions: Here we describe the preclinical evidence supporting the possible repositioning of TAK-475 from its originally intended use to the treatment of MKD and discuss its potential to modulate the mevalonate pathway in inflammatory diseases.

An experience of performing spirometry by trained general practitioners

2020 ◽  
pp. 34-36
Author(s):  
M. A. Pokhaznikova ◽  
E. A. Andreeva ◽  
O. Yu. Kuznetsova
Keyword(s):  
General Practitioners ◽  
Quality Criteria ◽  
Poor Quality ◽  
Male Gender ◽  
Study Research ◽  
The Poor ◽  
Quality Of Research ◽  
Forced Expiratory Maneuver ◽  
Maximal Effort

The article discusses the experience of teaching and conducting spirometry of general practitioners as part of the RESPECT study (RESearch on the PrEvalence and the diagnosis of COPD and its Tobacco-related aetiology). A total of 33 trained in spirometry general practitioners performed a study of 3119 patients. Quality criteria met 84.1% of spirometric studies. The analysis of the most common mistakes made by doctors during the forced expiratory maneuver is included. The most frequent errors were expiration exhalation of less than 6s (54%), non-maximal effort throughout the test and lack of reproducibility (11.3%). Independent predictors of poor spirogram quality were male gender, obstruction (FEV1 /FVC<0.7), and the center where the study was performed. The number of good-quality spirograms ranged from 96.1% (95% CI 83.2–110.4) to 59.8% (95% CI 49.6–71.4) depending on the center. Subsequently, an analysis of the reasons behind the poor quality of research in individual centers was conducted and the identified shortcomings were eliminated. The poor quality of the spirograms was associated either with the errors of the doctors who undertook the study or with the technical malfunctions of the spirometer.

Psychological influences on wound healing

2019 ◽  
Vol 98 (8) ◽  
pp. 312-314
Keyword(s):  
Wound Healing ◽  
Enhanced Recovery ◽  
Enhanced Recovery After Surgery ◽  
Wound Complications ◽  
State Of Mind ◽  
Life Threatening ◽  
Psychological Influences ◽  
Fear And Anxiety ◽  
Care Costs

Surgical wound complications remain a major cause of morbidity; although usually not life threatening, they reduce the quality of life. They are also associated with excessive health care costs. Wound healing is affected by many factors – wound characteristics, infection, comorbidities and nutritional status of the patient. In addition, though, psychological stress and depression may decrease the inflammatory response required for bacterial clearance and so delay wound healing, as well. Although the patient´s state of mind can be influenced only to a certain extent, we should nevertheless stick to ERAS (Enhanced Recovery After Surgery) guidelines and try to diminish fear and anxiety by providing enough information preoperatively, pay due attention to postoperative analgesia and seek to provide an agreeable environment.

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