Elevated Creatine Kinase Research Articles

A novel mutation in TANGO2 gene associated with recurrent muscle weakness with rhabdomyolysis , metabolic encephalopathy and cardiac arrhythmia: a case report

Background TANGO2 depletion was found to cause clinically recognizable multi-organ involvement disorder in pediatrics with episodic muscle weakness recurrent rhabdomyolysis, intellectual disability, metabolic encephalomyopathic crises and cardiac arrhythmia. TANGO2 deficiency is also referred to as \"metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration\" (MECRCN) in OMIM. * 616830 Case presentation We report a case of a 4-year-old Saudi boy from a consanguineous Saudi family with two uncles deceased at 3 year of age with recurrent muscle weakness and hyperammonemia of unknown cause .Patient in last attack progressed to severe metabolic encephalomyopathic crisis that required assisted ventilation for 4 months, complicated with life threatening cardiac tachyarrhythmia. Laboratory findings of hypoglycemia, mild hyperammonemia , severely elevated plasma Creatine Kinase, myoglobinuria , lactic acidosis and increased TSH concentration indicating hypothyroidism have been documented. The clinical profile was highly suggestive of TANGO2-realted disorder. Direct DNA sequence analysis of the entire coding regions of TANGO2 gene identified a novel homozygous deletion for three nucleotides in exon 2 (c.11_13delTCT) resulting in amino acid deletion (phenylalanine) at position 5. Conclusion This report illustrates the importance of collating clinical data and keeping a high index of suspicion in order to reach to the diagnosis.

Causes of HyperCKemia in Children: A Retrospective Cohort Study.

Background and Objectives: Creatine kinase (CK) is a commonly used screening test for neuromuscular disorders (NMDs). However, hyperCKemia can result from several pathologic and physiologic causes. We analyzed neuromuscular disorders in noninfant children with hyperCKemia including those with no weakness and mild CK elevations (<5 times the upper limit of normal). We hypothesized that children with mild CK elevation and no weakness would be unlikely to have neuromuscular disorders and require additional evaluation. Methods: We retrospectively evaluated patients between 1 and 18 years of age seen at a single children's hospital over a 3-calendar-year period with initial total CK values greater than the upper limit of normal with at least 2 years of follow-up data. Final diagnoses were analyzed and associations with possible risk factors assessed. Receiver operating characteristic curves were generated to assess altering CK cutoff values. Results: Of 260 subjects with hyperCKemia, 18 had a neuromuscular disorder (6.9%, 95% confidence interval [CI] 4.2%-10.9%). Of 166 subjects with CK <5 times the upper limit of normal and no weakness, 8 had a neuromuscular disorder (4.8%, 95% CI 2.3%-9.6%). Weakness (odds ratio [OR] 32.5, 95% CI 4-385, P = .0002), and family history of neuromuscular disorders (OR not calculable, P = .0003) were associated with neuromuscular disorders. An optimal CK threshold of 777 was identified on receiver operating characteristic curve analysis (sensitivity of 72% and specificity of 64%). The most commonly identified neuromuscular disorders were muscular dystrophies, inflammatory myopathies, and metabolic myopathies. Conclusion: Most children with hyperCKemia will not be diagnosed with a neuromuscular disorder, but a significant minority even with mild hyperCKemia and without weakness may warrant additional evaluation.

Characterization of Immune Checkpoint Inhibitor-Induced Myasthenia Gravis Using the US Food and Drug Administration Adverse Event Reporting System.

Myasthenia gravis (MG) is a rare but fatal adverse event of immune checkpoint inhibitors (ICIs). We assessed whether patient characteristics differed between those with ICI-related myasthenia gravis and those with idiopathic myasthenia gravis. Reports from the US Food and Drug Administration Adverse Event Reporting System were analyzed. Multivariate analyses were conducted to evaluate the associations between age, sex, and ICI treatment and the reporting rate of myasthenia gravis. Among 5 464 099 cases between 2011 and 2019, 53 447 were treated with ICIs. Myasthenia gravis was reported more often in ICI users. Multiple logistic regression analyses showed that the reporting rate of ICI-related myasthenia gravis did not differ significantly between men and women; however, it was higher in older people than in younger people (adjusted odds ratio, 2.4 [95%CI, 1.84-3.13]). We also investigated useful signs for the early detection of myositis and myocarditis, which are fatal when overlapping with ICI-related myasthenia gravis. Patients with elevated serum creatine kinase or troponin levels were more likely to have concurrent myositis and myocarditis. Unlike idiopathic myasthenia gravis, there was no sex difference in the development of ICI-related myasthenia gravis, which may be more common in older people. Considering the physiological muscle weakness that occurs in the elderly, it may be necessary to monitor ICI-related myasthenia gravis more closely in older people.

Assessment of Seminal Plasma Creatine Kinase Activity and Malondialdehyde Concentration among Normozoospermia but Infertile Men

Background: Despite the considerable research efforts that have been made by Reproductive Biologists to understand the etiologies of male infertility, idiopathic male factor infertility still remains unexplained. It occurs in about 10% cases of infertility. Since the etiologies cannot be identified using routine semen analysis, it is important to identify cellular and sub-cellular sperm complications that may help to explain the cause(s) of the infertility, thus stimulate caregivers to direct the further work-up, diagnosis and counseling of affected individuals. The objective of this study was to determine seminal plasma creatine kinase (CK) activity and malondialdehyde (MDA) concentration among normozoospermia but infertile males. Materials and Methods: After routine semen analysis, seminal plasma CK activity and MDA were determined among 75 normozoospermia but infertile men and 50 men of proven fertility using spectrophotometric method. Unpaired Students-t-test and regression analysis were used to compare and associate CK activity and MDA concentration with sperm characteristics. Results: Significantly higher (p&lt;0.001) level of MDA and CK activity were observed among infertile subjects than control group. Sperm count, percent motility, and viability were significantly lower (p&lt;0.05) among study participants than control subjects. Similarly, percentage abnormal morphology was significantly higher (p&lt;0.05) among infertile subjects than control group. The Odds of elevated CK activity to impair sperm motility, viability and morphology were 9.12(CI 102.6, 318.3), 3.18 (CI 129.9, 170.8) and 1.9 (CI 192.2, 208.1) times respectively higher among infertile group than controls. Similarly, the Odds of higher levels of MDA to impair sperm cell motility, viability and morphology were 5.02(CI 2.14, 4.6), 2.26(CI 2.34, 3.64) and 2.9 (CI 2.12, 3.73) times respectively higher among infertile group than control subjects. Conclusions: The seminal plasma CK activity and MDA constitute good indicators of functional metabolic activity and fertility potentials of spermatozoa among subjects with unexplained infertility.

138 OUTCOME AND MORPHO-FUNCTIONAL CHANGES ON CARDIAC MAGNETIC RESONANCE IN PATIENT WITH ACUTE MYOCARDITIS FOLLOWING MRNA COVID 19 VACCINATION

Abstract Background MessengerRNA (mRNA) COVID-19 vaccination has been associated with a higher-than-expected occurrence of acute myocarditis. Scarce information is available on mid-term prognosis and changes in cardiac function, volumes, and tissue characterization on cardiac magnetic resonance (CMR). Methods Retrospective, multicenter study including patients with a definite diagnosis of acute myocarditis within 30 days from mRNA COVID-19 vaccination, with a confirmed myocarditis diagnosis based on endomyocardial biopsy (EMB) or autopsy or by the coexistence of positive biomarkers (troponin &amp;gt;99th upper reference limit or elevated creatine kinase myocardial band [CK-MB]) and cardiac MRI findings consistent with AM according to the 2018 updated Lake Louise Criteria. Results 77 patients (median age 25 years [IQR 20-35], 15% female) were included and followed-up for 147 days [IQR 74-215]. Follow-up CMR was available in n=49 patients and showed no changes in biventricular ejection fraction (EF) as compared to CMR at diagnosis (left ventricular EF: 59%[55-65]vs. 60%[57-64], p=0.507, right ventricular EF: 56%[52-62]vs. 57%[52-61], p=0.563, respectively). Late gadolinium enhancement was present in all patients at diagnosis and persisted in only n=39 (79.6%) at follow-up (p=0.001), generally sparing the anterior wall and the septum. N=10 (20.4%) had a persistent edema based on T2-weighted short tau inversion recovery (STIR) sequences, with predominant involvement of inferior or inferior-lateral walls. The proportion of patients with increased T1 and T2 mapping signals significantly decreased at follow-up (n=13 (68%) vs. n=4 (13%),p&amp;lt;0.001, and n=21 (84%) vs. n=3 (10%),p&amp;lt;0.001, respectively), as well as the presence of pericardial effusion (n=16 (33%) vs. n=3 (6%),p=0.004). No differences in morpho-functional CMR parameters based on the type of vaccine administered were found (BNT162b2 Pfizer/BioNTech®, n=36, 73.5%, m-RNA-1273 Moderna®, n=13, 26.5%). Among patients with available follow-up (N=75, 97.4%), no major adverse cardiovascular events nor myocarditis recurrence or death were reported. Conclusions At mid-term follow-up, patients who experienced an acute myocarditis after a mRNA COVID-19 vaccine had preserved biventricular EF. The rate and localization of residual scar or edema on CMR is in line with classic viral myocarditis with a good prognosis. This new piece of information should further reassure patients who experience acute myocarditis after mRNA COVID-19 vaccination.

Elevated body temperature and leukocyte count are associated with elevated creatine kinase after seizures

ObjectiveTo evaluate the independent risk factors for elevated creatine kinase (hyperCKemia) after seizures. MethodsData included in this retrospective study were obtained from two hospitals from July 1, 2017, to March 31, 2022. Clinical and laboratory data were acquired from the emergency department or within 24 h after patient admission. Variables that exhibited statistical differences (P < 0.05) were selected for further analysis. Associations between body temperature (BT), leukocyte count (LEU), percentage of neutrophils (NEU), and C-reactive protein (CRP) and creatine kinase (CK) levels were assessed using binary logistic regression analysis. ResultsOne hundred twenty-three patients who exhibited seizures were included in the study, and 39 (31.7%) patients exhibited hyperCKemia based on a CK level that was >1.5 times the upper limit of the normal range for CK. No statistical differences were observed among the patient characteristics, seizure-related parameters, or electrolyte levels. However, BT, LEU, NEU, and CRP were elevated in patients with hyperCKemia compared to patients with normal CK levels. Specifically, a BT ≥ 37.5 °C (fever) and LEU >9.5×109/L (elevated LEU) exhibited positive correlations with hyperCKemia, and presented an adjusted OR of 8.87 (95% CI: 2.11–37.24, P = 0.003) and 3.01 (95% CI: 1.12–8.05, P = 0.029), respectively. ConclusionIn this study, hyperCKemia occurred in 31.7% of patients after seizures. Fever and elevated LEU were independent risk factors for seizure-related hyperCKemia. Earlier recognition of risks for seizure-related hyperCKemia would be beneficial in taking prophylactic measures.

An Interesting Case of Inflammatory Myositis

Background: Idiopathic inflammatory myopathies (IIM) are a class of long-lasting autoimmune diseases that typically affect the proximal muscles. Dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myopathy (NAM), and sporadic inclusion body myositis are the most prevalent kinds. Patients usually have subacute to chronic proximal weakness, which presents as difficulty getting out of a chair, getting up the stairs, lifting objects, and brushing their hair. They are distinguished by their clinical presentation, which includes muscular and extramuscular signs. Elevated serum creatine kinase (CK) levels and myositis-specific antibodies may help distinguish clinical phenotypes and confirm the diagnosis. Biopsy of the muscle, on the other hand, is still the gold standard for determining the cause of the problem. These disorders may be cured with proper diagnosis and treatment. The treatment’s goals are to reduce inflammation, restore muscle performance, and alleviate pain. Methods: 36-year-old man K/C/O dermatomyositis came complaints of redness swelling in the right eye for 3 months, dysphagia, easy fatiguability. Patient was neither hypertensive nor diabetic. Results: This case describes the severity of NXP2 autoantibody and a potential to be life threatening. Patient was started with immunoglobulins, monoclonal antibodies. After which patient improved from his present condition.

Safety and efficacy of switching to pemafibrate from bezafibrate in patients with chronic liver disease.

Although fibrates were developed as lipid-lowering drugs, their efficacy against liver dysfunction in patients with cholestatic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and fatty liver disease, has also been reported. Although fibrates act on some peroxisome proliferator-activated receptors (PPARs), pemafibrate is a novel selective PPAR-α modulator. The present study aimed to evaluate the safety and efficacy of switching from bezafibrate to pemafibrate in patients with chronic liver disease. We analyzed 58 patients with chronic liver disease who switched from bezafibrate to pemafibrate because of minor adverse effects and/or incomplete response. This study included 41 patients with cholestatic liver disease and 17 patients with non-alcoholic fatty liver disease. Reasons for switching to pemafibrate were renal function decline in 31 patients, hemoglobin decline in 17 patients, creatine kinase (CK) elevation in 11 patients, incomplete response of liver dysfunction in 39 patients, and incomplete response of hyperlipidemia in 13 patients. After 3months, although no significant change in CK was seen, hemoglobin and estimated glomerular filtration rate were significantly increased, and creatinine was significantly decreased. Significant decreases in hepatobiliary enzymes were seen in patients with cholestatic liver diseases, but not in patients with non-alcoholic fatty liver disease. No significant changes in serum lipids were observed. No patients discontinued pemafibrate due to adverse events. Switching to pemafibrate could improve adverse effects due to bezafibrate, and appeared effective against liver dysfunction in cholestatic liver disease patients with incomplete response to bezafibrate.

Application of deep learning-based diagnostic systems in screening asymptomatic COVID-19 patients among oversea returnees.

Our study aimed to investigate the performance of deep learning (DL)-based diagnostic systems in alerting against COVID-19, especially among asymptomatic individuals coming from overseas, and to analyze the features of identified asymptomatic patients in detail. DL diagnostic systems were deployed to assist in the screening of COVID-19, including the pneumonia system and pulmonary nodules system. 1,917 overseas returnees who underwent CT examination and rRT-PCR tests were enrolled. DL pneumonia system promptly alerted clinicians to suspected COVID-19 after CT examinations while the performance was evaluated with rRT-PCR results as the reference. The radiological features of asymptomatic COVID-19 cases were described according to the Nomenclature of the Fleischner Society. Fifty-three cases were confirmed as COVID-19 patients by rRT-PCR tests, including 5 asymptomatic cases. DL pneumonia system correctly alerted 50 cases as suspected COVID-19 with a sensitivity of 0.9434 and specificity of 0.9592 (within 2 minutes per case); while the pulmonary nodules system alerted 2 of the 3 missed asymptomatic cases. Additionally, five asymptomatic patients presented different characteristics such as elevated creatine kinase level and prolonged prothrombin time, as well as atypical radiological features. DL diagnostic systems are promising complementary approaches for prompt screening of imported COVID-19 patients, even the imported asymptomatic cases. Unique clinical and radiological characteristics of asymptomatic cases might be of great value in screening as well. DL-based systems are practical, efficient, and reliable to assist radiologists in screening COVID-19 patients. Differential features of asymptomatic patients might be useful to clinicians in the frontline to differentiate asymptomatic cases.

An experimental model of contusion injury in humans.

Contusion injuries are common in sport, but our knowledge of the responses to injury primarily come from animal studies and research using eccentric exercise. Therefore, the aim of this study was to develop a model of contusion injury in human participants and, additionally, investigate and compare physiological responses to four impact loads. Thirty-two males were exposed to a single impact of either 4.2, 5.2, 6.2 or 7.2kg, dropped from 67 cm, on to the vastus lateralis of one leg. Maximum voluntary and electrically induced quadriceps force, and pressure pain threshold were measured, and blood sampling carried out, prior to and 30min, 24, 48 and 72h post-impact. Magnetic resonance imaging was carried out 24h post-impact to quantify oedema. Despite impact force with 7.2kg (1681.4 ± 235.6 N) not being different to 6.2kg (1690.7 ± 117.6 N), 7.2kg resulted in greater volume of oedema, voluntary force loss, pain and elevations in creatine kinase than the other loads. Although electrically induced force changed over time, post-hoc analysis failed to identify any changes. Interleukin-6 and prostaglandin-E2 did not change over time for any of the loads. Significant correlations were found between oedema volume, pressure pain threshold and maximum voluntary contraction force. This is the first experimental study to investigate traumatic loading of skeletal muscle and the subsequent physiological responses associated with contusion injuries in humans. The absence of immediate elevations in creatine kinase and changes in electrically induced force suggest impact, with forces similar to those experienced in contact sport, does not cause significant, direct damage to skeletal muscle. However, the relationship between oedema volume, changes in pressure pain threshold and maximum voluntary contraction force suggests central inhibition plays a role in contusion-related muscle dysfunction.

Clinical Characteristics and Risk Prediction Score in Patients With Mild-to-Moderate Coronavirus Disease 2019 in Japan.

Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, causing widespread mortality. Many patients with COVID-19 have been treated in homes, hotels, and medium-sized hospitals where doctors were responsible for assessing the need for critical care hospitalization. This study aimed to establish a severity prediction score for critical care triage. We analyzed the data of 368 patients with mild-to-moderate COVID-19 who had been admitted to Fussa Hospital, Japan, from April 2020 to February 2022. We defined a high-oxygen group as requiring ≥4 l/min of oxygen. Multivariable logistic regression was used to construct a risk prediction score, and the best model was selected using a stepwise selection method. Multivariable analysis showed that older age (≥70 years), elevated creatine kinase (≥127 U/L), C-reactive protein (≥2.19 mg/dL), and ferritin (≥632.7 ng/mL) levels were independent risk factors associated with the high-oxygen group. Each risk factor was assigned a score ranging from 0 to 4, and we referred to the final overall score as the Fussa score. Patients were classified into two groups, namely, high-risk (total risk factors, ≥2) and low-risk (total risk score, <2) groups. The high-risk group had a significantly worse prognosis (low-risk group, undefined vs. high-risk group, undefined; P< 0.0001). The Fussa score might help to identify patients with COVID-19 who require critical care hospitalization.

A case series of dermatomyositis following SARS-CoV-2 vaccination.

The most significant adverse events following SARS-CoV-2 vaccination are myocarditis and pericarditis. Myositis and dermatomyositis have been reported following SARS-CoV-2 infection, but vaccine-induced dermatomyositis (DM) has not been reported. Our case series aimed to characterize new onset dermatomyositis or disease-related flares following SARS-CoV-2 vaccination. A total of 53 patients from our institution with a new or pre-existing diagnosis of DM were recruited and consented. Phone interviews were conducted to obtain vaccination status and symptoms following vaccination. Electronic medical records were reviewed to extract age, sex, autoantibody profiles, comorbidities, immunomodulatory therapies, creatine kinase (CK) values, and SARS-CoV-2 vaccination dates from the provincial vaccination registry. For patients who reported disease flares, records were reviewed for the onset and nature of symptoms, extent of organ involvement and changes in immunomodulation. On average, patients received 2.62 vaccine doses (range 1-3 doses). A total of 3 of 51 patients (5.88%) experienced dermatomyositis symptoms following vaccination. Two patients were newly diagnosed with dermatomyositis, one requiring hospitalization. Reported symptom onset following vaccination ranged from 1 to 30 days. Of note, all of these patients had normal CK values, even though there was muscle biopsy-confirmed myositis in one patient. Eight patients in the cohort (15.1%) had asymptomatic CK elevation (<1.5 X ULN). New onset dermatomyositis or flare up of pre-existing dermatomyositis may be a rare complication in SARS-CoV-2 vaccination although no studies can support a true correlation. Several pathophysiologic mechanisms are proposed.

Neuromuscular symptoms in patients with RYR1-related malignant hyperthermia and rhabdomyolysis.

Malignant hyperthermia and exertional rhabdomyolysis have conventionally been considered episodic phenotypes that occur in otherwise healthy individuals in response to an external trigger. However, recent studies have demonstrated a clinical and histopathological continuum between patients with a history of malignant hyperthermia susceptibility and/or exertional rhabdomyolysis and RYR1-related congenital myopathies. We hypothesize that patients with a history of RYR1-related exertional rhabdomyolysis or malignant hyperthermia susceptibility do have permanent neuromuscular symptoms between malignant hyperthermia or exertional rhabdomyolysis episodes. We performed a prospective cross-sectional observational clinical study of neuromuscular features in patients with a history of RYR1-related exertional rhabdomyolysis and/or malignant hyperthermia susceptibility (n = 40) compared with healthy controls (n = 80). Patients with an RYR1-related congenital myopathy, manifesting as muscle weakness preceding other symptoms as well as other (neuromuscular) diseases resulting in muscle weakness were excluded. Study procedures included a standardized history of neuromuscular symptoms, a review of all relevant ancillary diagnostic tests performed up to the point of inclusion and a comprehensive, standardized neuromuscular assessment. Results of the standardized neuromuscular history were compared with healthy controls. Results of the neuromuscular assessment were compared with validated reference values. The proportion of patients suffering from cramps (P < 0.001), myalgia (P < 0.001) and exertional myalgia (P < 0.001) was higher compared with healthy controls. Healthcare professionals were consulted because of apparent neuromuscular symptoms by 17/40 (42.5%) patients and 7/80 (8.8%) healthy controls (P < 0.001). Apart from elevated creatine kinase levels in 19/40 (47.5%) patients and mild abnormalities on muscle biopsies identified in 13/16 (81.3%), ancillary investigations were normal in most patients. The Medical Research Council sum score, spirometry and results of functional measurements were also mostly normal. Three of 40 patients (7.5%) suffered from late-onset muscle weakness, most prominent in the proximal lower extremity muscles. Patients with RYR1 variants resulting in malignant hyperthermia susceptibility and/or exertional rhabdomyolysis frequently report additional neuromuscular symptoms such as myalgia and muscle cramps compared with healthy controls. These symptoms result in frequent consultation of healthcare professionals and sometimes in unnecessary invasive diagnostic procedures. Most patients do have normal strength at a younger age but may develop muscle weakness later in life.

ODP487 Iatrogenic Thyroid Storm Treated with Plasmapheresis

Abstract Presentation: A 25-year-old man presented to the ED with intentional multi-drug overdose onset 9PM on the night prior to admission. PMHx is significant for seizures, hypothyroidism, resting tremors, and smoking. The patient expressed frustration over his persistent hand tremors with depressed mood and took 25 tablets of 500mg Keppra, 30-40 tablets of 150 mcg Levothyroxine, and 25 tablets of 10mg propranolol. The patient denied any chest pain, SOB, nausea, vomiting, lightheadedness, fever, focal weakness, numbness or tingling, prior SI, rash, dysuria, or bleeding. Hospital Course: Vitals were T: 37 Celsius, HR: 92 BPM, 135/87 BP, RR: 18, and SpO2: 93%. Initial EKG showed sinus rhythm with 80 heart rate. The physical exam was significant for profuse diaphoresis and generalized tremors. There were no ST or T wave abnormalities indicating ischemia. The patient had a lab workup that was significant for a TSH of 0. 006, FT4 of &amp;gt;5, FT3 of 7. 09, and T4 of 22.77, after which he was placed on plasmapheresis. The FT4 trended downward to 2.56 after plasmapheresis. The patient experienced transient elevations in creatine kinase and bilirubin, but lab workup was otherwise unremarkable. The patient met admission criteria for inpatient psychiatry and discharged to a psych facility. Discussion Given the 7-day half-life of Levothyroxine, plasmapheresis was considered the best option to prevent fatal thyroid storm. This case also demonstrates the importance of how a multi-drug overdose can present more benign presentation with stable vitals. In this case, the effects of propranolol masked the initial symptoms of hyperthyroidism and decreased FT3 levels, indicating the importance to conduct a thorough history to manage polypharmacy drug overdoses. This case highlights plasmapheresis as an effective treatment modality for thyroid storm. Presentation: No date and time listed

ODP136 A Rare Case of Necrotizing Myopathy after Statin Use

Abstract Introduction Statin associated necrotizing autoimmune myopathy is an extremely rare side effects of stain use. The incidence is approximately 2-3/100,000 Patients treated with statins. It usually associated with significant proximal muscle weakness, strikingly elevated creatine kinase (CK) levels and persistent symptoms despitestatin discontinuation. Here, we present a case with necrotizing myopathy after statin use as a reminder to clinicians for appropriately suspicious of this phenomenon while on treatment of statins. Clinical case: A 35 year old male with a past medical history of Autism, Type 2 Diabetes Mellitus, Hyperlipidemia, and Hypertension was brought to emergency room for right leg pain. Family states he had difficulty walking for a few weeks and had a fall from couch a week ago. Initial Vitals showed HR at 134 bpm, temp 35.9, BP 157/85 mmHg, RR 19 breaths/min. Labs showed Creatinine. 3.29 mg/dL, CO2 24 mmol/L, Na 141 mmol/L, K 4.2 mmol/L, Ca 9.5 mg/dL, glucose 265 mg/dL, AST/ALT 914/919 units/L, CK&amp;gt;14,000 units/L, WBC 9.2 thou/mcL, Hb 12.6 g/dL, TSH 9.42 mcIU/mL, Free T3 1.41 pg/mL, Free T4 0.95 mcg/dL. Urinalysis showed large blood with RBC of 1. Myoglobin&amp;gt;8750 mcg/L. Neuro motor exam showed strength 4/5 in bilateral lower extremities. His home medications including atorvastatin 20 mg nightly for 2 years, metformin and olmesartan, which all had been held. He was treated for rhabdomyolysis with aggressive hydration and Creatinine was improving. However, CK continued trending up to 42,915 units/L on day 5 with unreleased symptoms of lower extremity weakness. Neurology was consulted. Differential diagnosis of myopathy were suspected. His CK was continue to trend up to 45,585 units/L on day 10. Decision was made to have muscle biopsy with pathology showed: necrotizing myopathy without any clear evidence of inflammation. Although some autoimmune necrotizing myopathy may not show inflammation like those seen with HMG-CR antibodies or signal recognition antigen antibodies. Autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR Ab) was above 550. Following the biopsy, he received IV Solu-medrol 1g daily×4 doses, and then PO Prednisone 80 mg daily and then tapered down to 40 mg daily. He was also promptly started on IVIG 400 mg/kg/day for 5 days and methotrexate 7.5 mg weekly. His CK started to improve, down to 5815 units/L three weeks later. No significant improvement of strength. Conclusion Our case demonstrates that the appropriate diagnosis of statin induced necrotizing autoimmune myopathy with muscle biopsy and HMGCR Ab. We also wanted to alert future clinicians to have an early suspicious of such rare side effect and initiate treatment as early as possible which may bring the maximum benefit for patients. Presentation: No date and time listed

Muscle magnetic resonance imaging abnormality in neuroleptic malignant syndrome: a case report

BackgroundNeuroleptic malignant syndrome (NMS) is a rare and occasionally fatal undesirable reaction to dopamine antagonists, and its phenotype is diverse owing to causative drugs. Classically, elevation of serum creatine kinase is described in NMS. Some reports have described muscular pathological findings; however, muscle magnetic resonance imaging (MRI) has not been reported previously.Case presentationA 63-year-old woman with a history of schizophrenia presented to our hospital with a high fever, excessive sweating, muscle weakness, and elevated serum creatine kinase levels. Muscle MRI revealed T2 high-intensity lesions in several muscles with gadolinium enhancement, and the pathology of the muscle biopsy showed a very mild presence of muscle fiber necrosis and regeneration with type 2c fibers without inflammation. Her symptoms resolved by treatment with levodopa/carbidopa, dantrolene. Finally, the patient was diagnosed with NMS.ConclusionsThis is the first report of muscle MRI abnormalities in a patient with NMS. Muscle MRI abnormalities in NMS may be associated with non-inflammatory myopathic changes. The cause of creatine kinase elevation cannot be explained by abnormal strong muscle contraction nor inflammation.

Effectiveness and safety of statins on outcomes in patients with HIV infection: a systematic review and meta-analysis

Statins are hypolipidaemic in human immunodeficiency virus (HIV) positive individuals. However, their effect on all-cause mortality and rate of discontinuation is unclear. We conducted a systematic review to evaluate the impact of statins on all-cause mortality, discontinuation rates, and risk of adverse effects among HIV patients on highly active antiretroviral therapy (HAART). We searched four electronic databases from inception until October 2021 for trials and cohort studies evaluating the effects of statin treatment versus placebo in HIV patients. Forty-seven studies involving 91,594 patients were included. Statins were associated with significantly lower risk of discontinuation (RR, 0.701; 95% CI 0.508–0.967; p = 0.031). The risk of all-cause mortality (RR, 0.994; 95% CI 0.561–1.588; p = 0.827), any adverse effects (RR, 0.780; 95% CI 0.564–1.077; p = 0.131) and, diabetes mellitus (RR, 0.272; 95% CI 0.031–2.393; p = 0.241) with statin treatment were lower but not statistically significant compared to placebo/control. Statin treatment was associated with a trend of higher but statistically insignificant risk of myalgia (RR, 1.341; 95% CI 0.770–2.333; p = 0.299), elevated creatine kinase (RR, 1.101; 95% CI 0.457–2.651; p = 0.830) and liver enzyme activities (RR, 1.709; 95% CI 0.605–4.831; p = 0.312). Clinicians should consider the nocebo effect in the effective management of PLWH on statins, who present with common adverse effects such as myalgia and, elevated levels of creatine kinase and liver enzymes.

A novel de novo KCNB1 variant altering channel characteristics in a patient with periventricular heterotopia, abnormal corpus callosum, and mild seizure outcome.

KCNB1 encodes the α-subunit of Kv2.1, the main contributor to neuronal delayed rectifier potassium currents. The subunit consists of six transmembrane α helices (S1-S6), comprising the voltage-sensing domain (S1-S4) and the pore domain (S5-P-S6). Heterozygous KCNB1 pathogenic variants are associated with developmental and epileptic encephalopathy. Here we report an individual who shows the milder phenotype compared to the previously reported cases, including delayed language development, mild intellectual disability, attention deficit hyperactivity disorder, late-onset epilepsy responsive to an antiepileptic drug, elevation of serum creatine kinase, and peripheral axonal neuropathy. On the other hand, his brain MRI showed characteristic findings including periventricular heterotopia, polymicrogyria, and abnormal corpus callosum. Exome sequencing identified a novel de novo KCNB1 variant c.574G>A, p.(Ala192Thr) located in the S1 segment of the voltage-sensing domain. Functional analysis using the whole-cell patch-clamp technique in Neuro2a cells showed that the Ala192Thr mutant reduces both activation and inactivation of the channel at membrane voltages in the range of -50 to -30 mV. Our case could expand the phenotypic spectrum of patients with KCNB1 variants, and suggested that variants located in the S1 segment might be associated with a milder outcome of seizures.

Effects of nocebo and drusebo in determining statin-induced muscle symptoms

Statins represent an important class of cardiovascular drugs for the prevention of atherogenic complications. However, despite the effectiveness of statins, non-adherence and discontinuation of therapy with these drugs is a problem worldwide. Reasons for not using statins in patients at high CV risk include statin-associated muscle symptoms (SAMS), which are not usually associated with significant elevations of serum creatine kinase. SAMS are the most common side effects of statins: 3–5% in RCTs, 15–20% in observational studies, and 60% in patient surveys. This range is possibly due to misinterpretation of symptoms, as well as patients’ expectation of harm from statin treatment (“statin fear”). The article highlights the problem of studying the role of nocebo and drusebo effects for SAMS, presents differences in definitions and methods of detection. The concept of the drucebo effect was proposed by the International Lipid Expert Group (ILEP, 2018) as a harm to the patient, unrelated to the pharmacological action of the drug (negative effect of the drucebo). The results of studies and meta-analyses evaluating the effects of nocebo and drusebo for SAMS are presented, in which no difference was found in the frequency and severity of muscle symptoms between statin and placebo; the nocebo rate was 90% of the statin effect, and the contribution of the drusebo effect to SAMS and statin discontinuation ranged from 38 to 78%. Also presented are current international guidelines and principles of patient management aimed at preventing discontinuation of statin use in connection with SAMS.

Protective effect of quercetin against 5-fluorouracil-induced cardiac impairments through activating Nrf2 and inhibiting NF-κB and caspase-3 activities.

5-Fluorouracil (5-FU) is a chemotherapy used to treat many types of cancer. Cardiotoxicity is one of the common drawbacks of 5-FU therapy. Quercetin (Qu) is a bioflavonoid with striking biological activities. This research aimed to assess the ameliorative effect of Qu against 5-FU-mediated cardiotoxicity. Thirty-five rats were allocated into five groups: control group (normal saline), 5-FU group (30 mg/kg, intraperitoneally), Qu group (50 mg/kg, oral), 25 mg/kg Qu+5-FU group, and 50 mg/kg Qu+5-FU. The experimental animals were received the above-mentioned drugs for 21 days. Results showed that 5-FU significantly elevated creatine kinase, lactate dehydrogenase, serum cholesterol and triglyceride, and upregulated troponin and renin mRNA expression. Additionally, cardiac oxidant/antioxidant imbalance was evident in elevated oxidants (malondialdehyde and nitric oxide) and depleted antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). 5-FU also downregulated the gene expression of nuclear factor erythroid 2-related factor 2. Furthermore, 5-FU significantly increased cardiac pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and upregulated gene expression of nuclear factor kappa-B. 5-FU significantly enhanced cardiac apoptosis through upregulating caspase-3 expression and downregulating B-cell lymphoma 2. Immunohistochemical and histopathological examinations verified the above-mentioned findings. However, all these changes were significantly ameliorated in Qu pre-administered rats. Conclusively, Qu counteracted 5-FU-mediated cardiotoxicity through potent antioxidant, anti-inflammatory, and anti-apoptotic effects.