Creatine Kinase Research Articles

ROLE OF BIOCHEMICAL MARKERS AMONG COVID-19 PATIENTS AND THEIR ASSOCIATION WITH SEVERITY OF DISEASE

Objectives: The present study was aimed to evaluate the levels of biomarkers (D-dimer, Procalcitonin [PCT], lactate dehydrogenase [LDH], interleukin [IL]-6, and C-reactive protein [CRP]) among coronavirus disease 2019 (COVID-19) patients visiting/admitted in Government Medical College Jammu and analyze their association with the severity of disease. Methods: The study was conducted on 100 COVID-19-positive patients 18–75 years of age of either sex, visiting/admitted in Government Medical College Jammu, for a period of 6 months. The serum glucose levels, creatine phosphokinase, LDH, liver function tests, renal function tests, and various biochemical COVID-19 markers such as CRP, serum ferritin, IL-6, D-dimer, and PCT were analyzed. Results: In the present study, it was observed that when patients were divided according to the severity of disease, there was a significant difference in the mean levels of total bilirubin, serum sodium, serum potassium, D-dimer, SpO2, and duration of symptoms in a mild and severe group of patients, while there was no significant difference in the parameters such as IL-6, ferritin, CRP, PCT, LDH, and other routine biochemistry parameters. When a comparison was done between both the groups according to SpO2, only the mean levels of serum total bilirubin were significant. Conclusion: Thus, it is concluded that serum bilirubin was significantly elevated in mild, moderate, and severe groups of patients. Further research should be conducted to find some biomarkers which are specific to COVID-19 only.

Triheptanoin in patients with long-chain fatty acid oxidation disorders: clinical experience in Italy

BackgroundLong-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD.MethodsThis retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported.ResultsPatients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients’ total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment.ConclusionsThe significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations.

Clinical Findings, Laboratory Results, Electrocardiography and Echocardiography Findings in Dairy Buffaloes with Theileriosis.

Tropical theileriosis is a tick-borne haemoprotozoan disease, and cardiac function assessment in buffaloes with theileriosis was poorly documented. The Present study was carried out from April 2022 to December 2022. Theileriosis was confirmed by microscopic examination of stained blood smears and lymphnode smearsfurther confirmed by PCR assay. Electrocardiography was performed byusing the base apex lead system, and echocardiography was performed byusing the right parasternal view. The incidence of theileriosis was 16.25% by examination of stained blood smears, and 30.42% by PCR examination in 240 buffaloes. Repeatedly noted clinical signs were the absence of rumination, anorexia, loss of milk yield, depressed demeanour, emaciation, hyperthermia, lymphadenopathy, tick infestation, tachycardia, cardiac arrhythmia, and increased intensity of heartbeat. Haematological findings disclosed decreased haemoglobin, packed cell volume, total erythrocyte count, and neutrophils; increased eosinophils and monocytes. Serum biochemical findings revealed decreased albumin, albumin/globulin ratio, glucose, calcium, phosphorous, sodium, potassium, and chloride; increased globulin, aspartate aminotransferase, bilirubin, blood urea nitrogen, creatinine, cholesterol, lactate dehydrogenase, gamma-glutamyl transferase, and creatine kinase myocardial band isoenzymes. Electrocardiography explorations were sinus tachycardia, broad T wave, and sinus arrhythmia. Echocardiography examination showed ventricular wall thickening, cardiac chamber dilatation, valvular defects/valvular regurgitation, and pericarditis/cardiac tamponade. The present research proposes the changes in the electrocardiography and echocardiography findings in buffaloes with theileriosis, which are essential in clinics to identify the secondary complications during theileriosis and formulate therapeutics.

Effect of Bezafibrate and Ginkgo biloba Extract Combination on Doxorubicin-Induced Cardiotoxicity in Rats

Objectives: This study aimed to evaluate the possible synergistic effect of bezafibrate and ginkgo biloba (GKB) extract on cardiotoxicity induced by doxorubicin. Methods: Thirty rats were allocated into 5 groups: The negative control group was treated daily with 1 ml of distilled water orally by gavage tube; the positive control received doxorubicin 3.7 mg/kg on day 11 for 3 days intraperitoneally; the bezafibrate group received 100mg/kg orally by gavage tube; the GKB group received 60mg/kg orally by gavage tube; and the combination of bezafibrate and GKB group. All the groups received the doxorubicin protocol, with an exception for the negative control. The treatment continued for 14 days. On day 14, blood samples were taken for the measurement of serum levels of troponin, natriuretic peptide, creatine phosphokinase (CPK), IL-6, and total lipid profile. The atherogenic index, cardiac risk, and LDL/HDL ratios were calculated. Cardiac tissues were sent for histopathological analysis. Results: Both bezafibrate and GKB exhibited attenuation of troponin, natriuretic peptides, CPK, IL-6, TG, cardiac risk ratio, and atherogenic index, as well as an increase in HDL levels. However, the combination group showed the greatest effect compared to the positive control group. The histopathological findings supported the biochemical outcomes. Conclusions: Combining GKB extract and bezafibrate protects against cardiac injury by restoring injury markers and IL-6, as well as improving the lipid profile, cardiac risk ratio, and atherogenic index.

Acute Changes in Hamstring Injury Risk Factors After a Session of High-Volume Maximal Sprinting Speed Efforts in Soccer Players.

Maximal sprinting speed (MSS) overexposure is associated with increased risk of injury. This study aimed to describe changes in sprint performance-related factors and hamstring strain injury (HSI) risk factors after a high-volume sprinting session in soccer players. A high-volume sprinting session can induce acute changes in several sprint performance-related factors (sprint time and mechanical properties) and HSI risk factors (posterior chain muscle strength, hamstring range of motion, and dynamic lumbo-pelvic control [LPC], measured as changes in anterior pelvic tilt [APT] during maximal speed sprinting). Prospective observational case series. Level 4. Fifteen active male amateur soccer players participated. Changes in sprint performance-related factors and HSI risk factors were examined for 72 hours after high-volume MSS efforts (H-VMSSE) using a soccer-contextualized multifactorial approach. Muscle damage proxy markers (hamstring perceived soreness and creatine kinase) were also examined. H-VMSSE induced decrements in sprint performance-related factors. Significant reductions in theoretical maximal horizontal velocity (P < 0.01; effect size [ES], -0.71) and performance (P = 0.02; ES, -0.59) were observed for 48 and 72 hours after H-VMSSE. Small but significant reductions in posterior chain muscle force-generating capacity were detected for 48 and 72 hours after H-VMSSE for the nondominant (P < 0.03; ES, -0.60) and dominant (P < 0.04; ES, -0.40) leg. Finally, players exhibited persistent small, albeit nonsignificant (P = 0.06; ES, 0.53), decreases in dynamic LPC (APT increases) for 72 hours after H-VMSSE. H-VMSSE induced declines in both sprint performance-related factors and HSI risk factors. Sprinting can alter a player's anatomic structure by increasing APT during the maximum speed phase of the sprint. A soccer-contextualized multifactorial approach might allow for the regulation of MSS dosage depending on individual HSI risk factor status, thereby serving as a tailored "vaccine" for sprinting needs.

Novel Variant in ANO5 Muscular Dystrophy: Identification by Whole Genome Sequencing and Quad Analysis.

The phenotypic spectrum of ANO5 muscle disease ranges widely from elevated creatine kinase (CK) levels in the serum of asymptomatic individuals to progressive muscular dystrophy. Due to overlapping clinical features among muscular dystrophies, the diagnosis of ANO5 muscle disease is established by molecular genetic tests. Early diagnosis is crucial for the clinical management of symptoms and to mitigate cardiac and musculoskeletal complications. Quad-joint analysis was performed on whole genome sequencing (WGS) data obtained from an 18-year-old female with mild myalgia and elevated CK and her unaffected parents and sister. The phenotype-driven analysis was performed to prioritize genomic alterations related to the phenotype. The zygosity-based analysis investigated compound heterozygous and de novo status for all variants. The quad-joint WGS analysis revealed a novel pathogenic heterozygous variant, ANO5:c.1770_1773del (p.Phe593Metfs*15), that was paternally inherited. A second and known pathogenic heterozygous variant, ANO5:c.148C>T (p.Arg50*), was also present that was maternally inherited. The genome finding led to the diagnosis of autosomal recessive ANO5 muscle disease and an early personalized clinical management for the patient regarding her cardiac and musculoskeletal health. This is the first report of the ANO5:c.1770_1773del variant in the literature. This report highlights the spectrum of ANO5 muscle disease and describes the role of quad-joint WGS in the early diagnosis and preventive clinical management of ANO5 muscle disease.

The spectrum of rippling muscle disease.

Rippling muscle disease (RMD) is a rare disorder of muscle hyperexcitability. It is characterized by rippling wave-like muscle contractions induced by mechanical stretch or voluntary contraction followed by sudden stretch, painful muscle stiffness, percussion-induced rapid muscle contraction (PIRC), and percussion-induced muscle mounding (PIMM). RMD can be hereditary (hRMD) or immune-mediated (iRMD). hRMD is caused by pathogenic variants in caveolin-3 (CAV3) or caveolae-associated protein 1/ polymerase I and transcript release factor (CAVIN1/PTRF). CAV3 pathogenic variants are autosomal dominant or less frequently recessive while CAVIN1/PTRF pathogenic variants are autosomal recessive. CAV3-RMD manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic creatine kinase elevation to severe muscle weakness. Overlapping phenotypes are common. Muscle caveolin-3 immunoreactivity is often absent or diffusely reduced in CAV3-RMD. CAVIN1/PTRF-RMD is characterized by congenital generalized lipodystrophy (CGL, type 4) and often accompanied by several extra-skeletal muscle manifestations. Muscle cavin-1/PTRF immunoreactivity is absent or reduced while caveolin-3 immunoreactivity is reduced, often in a patchy way, in CAVIN1/PTRF-RMD. iRMD is often accompanied by other autoimmune disorders, including myasthenia gravis. Anti-cavin-4 antibodies are the serological marker while the mosaic expression of caveolin-3 and cavin-4 is the pathological feature of iRMD. Most patients with iRMD respond to immunotherapy. Rippling, PIRC, and PIMM are usually electrically silent. Different pathogenic mechanisms have been postulated to explain the disease mechanisms. In this article, we review the spectrum of hRMD and iRMD, including clinical phenotypes, electrophysiological characteristics, myopathological findings, and pathogenesis.

7915 A Case of Severe Hypothyroidism in a Patient with Nephrotic Syndrome presenting with Rhabdomyolysis requiring Levothyroxine and Liothyronine combination therapy

Abstract Disclosure: S.S. Mohammed: None. E.T. Ngo: None. S. Tadisina: None. B.M. Drees: None. Background: Nephrotic syndrome is known to worsen hypothyroidism via urinary loss of thyroid binding globulin, transthyretin, albumin and other proteins, often requiring escalating levothyroxine doses. Severe uncontrolled hypothyroidism can result in rhabdomyolysis, although this presentation is quite rare. Clinical case: We present a case of a 50-year-old male with long-standing Hashimoto’s hypothyroidism, biopsy-proven minimal change disease with nephrotic syndrome, dyslipidemia, and hypertension, who was admitted for generalized myalgia, weakness, and progressive swelling of bilateral hands and feet for one month. He had been off levothyroxine 3 months prior to presentation. He previously required large doses of oral levothyroxine, as high as 350mcg daily, but never achieved a euthyroid state despite reported adherence to therapy with the high levothyroxine doses.Laboratory workup showed severe hypothyroidism (free thyroxine &amp;lt;0.25ng/dL [0.6-1.6ng/dL] with markedly elevated thyroid stimulating hormone 282.03 mIU/mL [0.3-5.6mIU/mL]), along with acute kidney injury and rhabdomyolysis (Creatine kinase 4882 U/L[38-234U/L]). He was hemodynamically stable with intact mentation and was not deemed to be in myxedema coma. Physical examination was consistent with hypothyroidism with periorbital swelling, dry skin, deep hoarse voice, bilateral hand and feet edema, and delayed deep tendon reflexes. Thyroid function tests and clinical symptoms failed to improve after 8 days, despite high doses of levothyroxine IV (200mcg). Creatine kinase remained high at 4994 U/L [38-234U/L] despite adequate fluid hydration. Liothyronine 5mcg orally was started in addition to levothyroxine 200mcg IV. Repeat thyroid function tests after 2 days of combined IV levothyroxine and oral liothyronine therapy showed significant downtrend in TSH to 154.12 uIU/ml [0.3-5.6mIU/mL] and increase in free thyroxine to 0.44ng/dl [0.6-1.6ng/dL]. Creatine kinase also down trended to 3181U/L[38-234U/L] on D4 of IV levothyroxine 200mcg IV with liothyronine 5mcg daily. He was discharged stable and clinically improved on oral levothyroxine and liothyronine. Laboratory evaluation 10 days later showed further improvement in TFTs (TSH 66.0[0.3-5.6mIU/mL]), free thyroxine 0.6 [0.6-1.6ng/dL] Conclusion: This case presents a unique and unusual clinical course in symptomatic primary hypothyroidism with rhabdomyolysis and AKI. Rhabdomyolysis due to hypothyroidism, without an obvious precipitating factor, has been previously reported, but is very rare. There is limited evidence regarding combination treatment with levothyroxine and liothyronine in primary hypothyroidism; however, as demonstrated in this patient, combination therapy resulted in clinical and biochemical improvement of thyroid function. Presentation: 6/2/2024

7668 Rhabdomyolysis Associated with Severe Hypothyroidism

Abstract Disclosure: H. Soe: None. P. Mikkilineni: None. Background: Over 70% of the patients with newly diagnosed hypothyroidism can present with muscle complaints such as weakness, fatigability, cramps, myalgia. However, rhabdomyolysis, which is the rapid breakdown of skeletal muscle cells, is the rare presentation. Clinical Case: A 70-year old male patient with history of rheumatoid arthritis, hyperlipidemia, prior CVA (left hemispheric subcortical stroke) 6 months ago without residual deficit presented to the hospital with poor oral intake and generalized muscle weakness for 3 weeks. He was unable to get out of bed without assistance and also needed adult diapers. Found to have new-onset severe hypothyroidism with TSH 228 uIU/ml (Ref: 0.350-4.940) and FT4 &amp;lt;0.40 ng/dL (Ref: 0.70-1.50), positive TPO antibody 197 IU/ml (Ref: 0-34). No prior thyroid labs were available and no known history of thyroid disorder was recorded. He has never been on Amiodarone or Lithium before. On physical exam, he was alert and oriented. There was no goiter or palpable thyroid nodule. There was no focal neurological deficit and no peripheral edema. There were no other signs and symptoms pertinent to hypothyroidism except mild bradycardia (HR 56-60) and borderline low blood pressure. AM cortisol was 10.1 ug/dL (Ref: 3.7-19.4). EKG showed low-voltage sinus bradycardia. Echocardiogram was normal. Urinalysis was positive for large blood but only 3 RBCs were present which raised the suspicion of rhabdomyolysis. Creatinine kinase (CK) was 15,584 IU/L (Ref: 30-200). Other laboratory studies were significant for acute renal failure with mild hyperkalemia and mild hypocalcemia, also transaminitis; BUN 130 mg/dl (Ref: 8-26), Creatinine 9.51 mg/dl (Ref: 0.72-1.25), eGFR 5 ml/min/1.73 m2 (Ref: &amp;gt;59), AST 435 IU/L (Ref: 5-34), ALT 269 IU/L (Ref: &amp;lt;55), ALP 171 IU/L (Ref: 40-150). On medication review, he was started on Atorvastatin 80 mg daily during prior admission for CVA 6 months ago. He received IV fluids, s/p 1 dose of Hydrocortisone 100 mg IV, Levothyroxine IV 200 mcg, followed by Levothyroxine IV 50 mcg daily x 3 days and switched to Levothyroxine PO 100 mcg daily (weight-based dose). Atorvastatin was on hold. He became anuric during the hospital course and received 2-3 sessions of hemodialysis. 3-4 days later, CK was trending down to 3000 IU/L, FT4 improved to 0.54 ng/dl and there was also significant improvement in kidney and liver functions. The patient was diagnosed with acute renal failure secondary to rhabdomyolysis associated with severe hypothyroidism caused by Hashimoto's thyroiditis, in the setting of high dose statin use. Conclusion: Clinicians should raise the suspicion of rhabdomyolysis in a patient with severe hypothyroidism, especially in patients with recent high dose statin use as rhabdomyolysis can be a rare and fatal complication of severe hypothyroidism, in the presence of precipitating factors. Presentation: 6/2/2024

6928 Vitamin D excess in a patient with hypoparathyroidism after parathyroidectomy

Abstract Disclosure: Z. Zavgorodneva: None. A. Barsegian: None. F. Zhang: None. Introduction. We describe a case of a patient with mild persistent hypoparathyroidism after parathyroidectomy with autotransplantation, which was indicated for ESRD-related secondary hyperparathyroidism. The patient presented with nonspecific complaints and was found to have a high Vitamin D level after long-term moderate-dose Vitamin D supplementation. Case report. A 71-year-old male with a past medical history of end-stage renal disease (ESRD) undergoing hemodialysis for the past 18 years, as well as a history of parathyroidectomy with autoimplantation of parathyroid glands in the forearm in 2010 due to severe secondary hyperparathyroidism, presented to the hospital complaining of generalized weakness and lower extremity cramps that had been ongoing for a few weeks. Further investigations did not reveal evidence of infectious processes. A review of medications indicated the absence of statins among his outpatient medications. No focal neurological deficits or objective signs of muscle weakness were identified. Laboratory findings showed no significant metabolic derangements or haematological abnormalities. Inflammatory markers and creatine phosphokinase were within normal ranges. As part of the workup for generalized subjective weakness and ESRD, Vitamin D levels were checked, revealing a result of of120 ng/mL. The patient reported taking over-the-counter 2000 IU of Vitamin D twice daily for the past six years despite having a normal level of Vitamin D checked five years prior to admission. Calcium supplements were initiated in the postoperative period and continue to be administered at a dose of 600 mg daily. Analysis of the PTH-calcium axis demonstrated persistent mild hypoparathyroidism with hypocalcemia since the time of the surgery. However, there was an observed tendency for calcium levels to improve, especially in the last six years. Vitamin D supplement was discontinued, and the patient was subsequently discharged home with the continuation of physical therapy. Discussion. Explaining the origin of the high level of Vitamin D in this patient poses a challenge. There is limited data in the literature regarding the long-term effects of vitamin D use when the initial Vitamin D levels are normal. Additionally, there are numerous abstracts suggesting significantly higher doses of Vitamin D received for up to 6 years without any evident biochemical or clinical consequences. Moreover, the typical consequences of Vitamin D toxicity, such as hypercalcemia, can not be present in patients who underwent parathyroidectomy. Therefore, it is possible to consider that the severe generalized subjective weakness may be a sign of Vitamin D toxicity itself. Presentation: 6/1/2024

6411 Ozempic - Oh no! Acute Renal Failure Associated with Initiation of Semaglutide

Abstract Disclosure: K. Barney: None. D. Tahir: None. A. Pannu: None. R. Saeed: None. Background: Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist which has been proven to reduce weight in those with obesity and improve glycemic control in patients with type II diabetes mellitus. The effect of semaglutide on kidney function has not been well established. The phase 3b SUSTAIN trials revealed that when compared with other GLP-1 agonists, semaglutide exhibited more frequent acute kidney injuries [1-3]. The SUSTAIN 6 trial reported two instances of acute renal failure (ARF) in patients with chronic kidney disease, and one case of ARF in a patient with normal kidney function who was treated with semaglutide [3]. Despite these reports, the SUSTAIN 1-9 trials report no significant decline in kidney function associated with semaglutide [3-6]. Case: We present the case of a 58-year-old male with a past medical history of human immunodeficiency virus (HIV), type II diabetes mellitus, and hypertension who presented to the hospital with ARF after initiation of Ozempic (semaglutide) two months prior to presentation. On admission, vitals were stable and physical examination was benign. His pertinent labs were blood urea nitrogen (BUN) 55 mg/dL, creatinine 5.94 mg/dL (baseline 1.2 mg/dL), and urinalysis with 2+ protein. To determine the cause of his renal failure, urine sodium and creatinine were obtained to calculate his fractional excretion of sodium, which was found to be consistent with intrinsic renal disease. Further workup, including renal ultrasound, urine protein, urine eosinophils, complement and free light chain levels, and creatinine kinase, were unrevealing for cause of intrinsic renal injury. He was managed with intravenous fluids and his creatinine improved to 2.03 mg/dL. Given the acute onset of the patient’s renal failure and recent initiation of Ozempic, it was determined that this medication was the cause of his renal failure, and it was discontinued on discharge. He has since followed up with nephrology and endocrinology. He remains off Ozempic and is doing well. Conclusions: Our case highlights a rare but significant adverse effect of semaglutide on renal function. As the use of semaglutide has increased due to its rising popularity for weight loss and glycemic control in type II diabetes mellitus, the potential for renal injury should be considered and discussed with patients. Furthermore, it is imperative that semaglutide associated renal injury be considered as a cause for ARF in patients taking this medication. This case demonstrates that instances of ARF associated with semaglutide treatment are a cause for concern and further exploration. Presentation: 6/1/2024

Anti-inflammatory effects of proprotein convertase subtilisin/kexin 9 inhibitor therapy in the early phase of acute myocardial infarction.

This study examined the anti-inflammatory and endothelial function-enhancing effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor therapy in the early phase after acute myocardial infarction (AMI) by assessing changes in tumor necrosis factor-α (TNF-α) levels and the L-arginine/asymmetric-dimethylarginine (ADMA) ratio. This retrospective, single-center cohort study included patients who underwent successful timely primary percutaneous coronary intervention (PCI) for first-onset AMI between September 2017 and March 2018. The PCSK9 inhibitor group comprised patients who received 75mg alirocumab up to 7days after AMI, while the standard therapy group comprised patients who did not. We evaluated the change in TNF-α levels and the L-arginine/ADMA ratio at the time of hospital admission and prior to discharge. PCSK9 inhibitor therapy in the early phase after AMI suppressed TNF-α levels (standard therapy group, 1.64 ± 2.14pg/mL vs. PCSK9 inhibitor group, 0.26 ± 0.33pg/mL; p = 0.033) and increased the L-arginine/ADMA ratio (standard therapy group, -13.0 ± 39.7 vs. PCSK9 inhibitor group, 23.2 ± 39.7; p = 0.042). Upon multiple regression analysis adjusted for sex, age, and peak creatine kinase levels, PCSK9 inhibitor therapy was associated with TNF-α suppression (p = 0.025; β = -0.235, 95% confidence interval [CI], -0.436 to -0.033). The L-arginine/ADMA ratio was also analyzed using multiple regression, adjusted for sex, age, peak creatine kinase levels, and smoking, showing a significant improvement in the ratio (p = 0.018; β = 41.913, 95% CI, 10.337-73.491). Moreover, a weak negative correlation was suggested between the change in TNF-α levels and the change in L-arginine/ADMA ratio (r = -0.393, p = 0.058). PCSK9 inhibitor therapy in the early phase after AMI suppresses TNF-α levels and improves the L-arginine/ADMA ratio, potentially indicating anti-inflammatory and endothelial function-enhancing effects.

5117 Unusual Sarcoid Presentation as a Case of Hypercalcemia

Abstract Disclosure: M. Salim: None. A. Chauhan: None. S. Avula: None. A. Ahmed: None. K. Zekarias: None. Background: Hypercalcemia may arise from a variety of causes and can pose challenging diagnostic dilemma. Clinical Case: An 89-year-old male presented with worsening malaise related to persistent hypercalcemia. He reported productive cough, polyuria, polydipsia, generalized muscle weakness and weight loss. Physical exam was remarkable for upper and lower extremities weakness. Laboratory tests showed calcium 11.6 (8.8-10.2 mg/dL), phosphorus 2.8 mg/dL (2.5-4.5 mg/dL), albumin 4.2 g/dL (3.5-5.2 g/dL), parathyroid hormone (PTH) 10 pg/mL (15-65 pg/mL), parathyroid hormone-related protein (PTH-rp) 4.5 pmol/L (0.0-2.3 pmol/L), TSH 6.24 (0.30 - 4.20 uIU/mL), free T4 1.10 ng/dL (0.90-1.70 ng/dL), GFR 61 mL/min/1.73m2, 25 OH Vit D 31 ng/mL (20-75 ng/mL), vit D 1,25-dihydroxy 134 pg/mL (19.9-79.3 pg/mL), calcium urine/creatinine 0.54. Hypercalcemia was first noted 11 months before the visit with a level of 14.0 mg/dL (8.8-10.2 mg/dL), phosphorus 3.5 mg/dL, PTH 11, PTH-rp 1.4 pmol/L, 25 OH Vit D 62 ng/mL, Vit D 1,25-dihydroxy 90 pg/mL, angiotensin-1-converting enzyme 12 U/L (16-85 U/L), serum and urine electrophoresis showed no monoclonal gammopathy present, and tuberculosis interferon-gamma test negative. Autoimmune workup was unremarkable, except for weak positive anti-signal recognition particle (SRP) antibodies and anti-Mi-2 antibodies. CT chest/pelvis/abdomen demonstrated peripheral predominant reticular opacities suggestive of interstitial lung disease and no malignant findings. Treatment history included zoledronic acid 11 months before the visit. The patient was referred for a granulomatous disease workup.Upon one month follow-up, the hypercalcemia symptoms were worsening. Repeat calcium was 12.3 mg/dL and fungal serologies were negative. The patient was started on prednisone empirically. PET CT was ordered and revealed patchy inflamed musculature of extremities suspicious of dermatomyositis/polymyositis. Further labs showed unremarkable myomarker panel, u3-Hydroxy-3-Methylglutaryl Coenzyme A reductase (HMGCR) antibody, Anti-cN-1A antibody, ACE 53 U/L, creatine kinase 32 U/L (39-309 U/L), aldolase 5.4 U/L (1.2-7.6 U/L), soluble IL-2R 1,021 U/mL (137-838 U/mL), and lysozyme 3.89 ug/mL (&amp;lt;2.75 ug/mL). A muscle biopsy was done, which showed benign skeletal muscle with patchy myofiber atrophy, patchy interstitial fibrosis, and focal interstitial mild chronic inflammation with no evidence of sarcoid granulomas in the sample. One week lab follow-up post initiation of steroid showed calcium of 10.1 mg/dL and subsequently improvement in his overall labs. Working diagnosis of sarcoid myositis was made. Conclusion: This case report highlights the approach of diagnosing a rare case of hypercalcemia due to sarcoid myositis. In a highly clinical suspicious patient, PET CT scan might be a necessary modality for diagnosis. Presentation: 6/2/2024

6769 Rhabdomyolysis In Diabetic Emergencies Highlighting The Necessity Of Prompt Creatine Kinase Monitoring

Abstract Disclosure: A. Tiwari: None. M. Corsten: None. W. salari: None. N. Malik: None. A. Dabaja: None. C. Saad: None. Rhabdomyolysis results from skeletal muscle necrosis, causing the release of intracellular contents into the bloodstream. While its association with life-threatening diabetic emergencies is rare, it remains a significant complication. We detail the case of a 37-year-old male admitted with acute pancreatitis who subsequently developed a hyperosmolar hyperglycemic state accompanied by significant electrolyte imbalances. Upon arrival at our emergency department, he displayed severe dehydration, stupor, a blood glucose level surpassing 2,000 mg/dl, and high anion gap metabolic acidosis. His condition worsened when his creatine kinase levels surged from 210 U/L to 39,000 U/L, leading to oliguric renal failure and the need for hemodialysis. His thyroid profile was unremarkable and was not on any medication. Comprehensive treatment included crystalloids, parenteral insulin, and rigorous ICU monitoring with mechanical ventilation. Following this, the patient showed rapid improvement and was discharged without requiring further dialysis. A thorough history and observation established a rare but strong link between rhabdomyolysis and hyperosmolar hyperglycemic states. These situations can intensify nephrotoxic events, especially in patients already facing severe dehydration and prerenal factors. This case emphasizes the critical need for consistent monitoring of creatine kinase levels in diabetic emergencies. Such monitoring ensures early detection and facilitates effective management of rhabdomyolysis-induced acute kidney injury, reducing potential complications and improving patient outcomes. Presentation: 6/3/2024

8165 A Case Of Rhabdomyolysis-Induced Hypocalcemia And Hypercalcemia

Abstract Disclosure: A. Desai: None. A.L. Izzi: None. B. Flores Chang: None. A. Sajan: None. Introduction: Rhabdomyolysis is a syndrome characterized by muscle breakdown and the release of intracellular muscle contents into circulation. It is associated with electrolyte abnormalities and acute renal failure that can lead to prolonged hospitalization. We report a case of persistent hypercalcemia from recovery of acute renal failure and severe rhabdomyolysis. Case Description: A 47-year-old man with past medical history of polysubstance use initially presented with opiate-induced acute encephalopathy and respiratory failure. He developed severe rhabdomyolysis during the hospital course leading to acute renal failure requiring hemodialysis with hypocalcemia. The initial labs showed corrected calcium 6.2 mg/dL [9.2-11.0], ionized calcium 3.48 mg/dL [4.65-5.28], creatinine kinase level was &amp;gt;72,600 U/L [38-174], BUN 110 mg/dL [8-23], creatinine 7.8 mg/dL [0.6-1.2], and GFR 7 ml/min/BSA. His renal function improved over the next several days in the hospital. The serum creatinine improved to 4 mg/dL, BUN 49 mg/dL and GFR 20 ml/min/BSA respectively after couple of intermittent dialysis sessions. Six days after the last hemodialysis session, patient developed severe hypercalcemia with corrected calcium values ranging from 13.5 to 14.7 mg/dL and ionized calcium 7.41 mg/dL. Labs showed PTH 10 pg/mL [15-65], 1,25-dihydroxyvitamin D &amp;lt;10.0 pg/dL [21-65] and 25-OH Vitamin D levels 15.3 ng/ mL [30-96], which is consistent non-PTH medicated hypercalcemia. The 24-hour urine calcium was 696 mg [0-300 mg/24 hrs, 2900 cc]. PTH-related peptide was not collected. He was treated with intermittent doses of calcitonin and a single dose of pamidronate when the calcium levels were &amp;gt;13 mg/dL. Hypercalcemia resolved in eleven days after initially noted to have hypercalcemia. The corrected calcium improved to 10.1 mg/dL on the day of discharge. Discussion:Severe rhabdomyolysis is associated with acute kidney injury. The initial hypocalcemic phase during rhabdomyolysis is due to entry of calcium into damaged myocytes and deposition of calcium salts in damaged muscle. This is seen in the oliguric phase of acute kidney injury. After the recovery of rhabdomyolysis, the polyuric phase persists during renal recovery. During this time, up to one third of patients may have rebound hypercalcemia due to massive muscle calcium release. As per case reports the hypercalcemia phase lasts from 8 days to 3.5 months. In our case, the patient initially developed hypocalcemia in the oliguric phase of acute kidney injury from rhabdomyolysis. He developed hypercalcemia in the polyuric phase of renal recovery. The hypercalcemia resolved with intravenous hydration, calcitonin and pamidronate. Rhabdomyolysis is a rare cause for both hypocalcemia and hypercalcemia. Our case highlights the biphasic calcium response associated with rhabdomyolysis in the setting of renal impairment and recovery. Presentation: 6/1/2024

6541 Recurrent Euglycemic Diabetic Ketoacidosis And Myonecrosis In A Patient Previously Thought To Have Type 2 Diabetes Mellitus

Abstract Disclosure: K. Haridas: None. M.M. McConnell : None. Introduction: Euglycemic diabetic ketoacidosis (DKA) is a well-recognized complication with the use of sodium linked cotransport of glucose-2 (SGLT2) inhibitors. Diabetic myonecrosis is a rare complication of diabetes mellitus caused by spontaneous death of muscle due to microvascular ischemia. Clinical Case: A 48-year-old male diagnosed with Type 2 Diabetes Mellitus with HbA1c 11.3%, treated with Empagliflozin and basal-bolus insulin was admitted to the hospital with left thigh pain and anorexia. Physical examination was notable for BMI of 19kg/m2 and left lateral thigh induration. Laboratory evaluation revealed venous pH 7.1, bicarbonate 10mmol/L (20-30), anion gap 32mmol/L(8-12), glucose 168mg/dl (65-99), ESR 67mm/h (&amp;lt;=12), Creatinine Kinase 31 U/L (63-473), glucosuria (4+) and ketonuria (4+). He was diagnosed with euglycemic DKA due to SGLT2 inhibitor. He was also diagnosed with Type 1 Diabetes Mellitus (T1DM) based on undetectable C-peptide and GAD antibody titer 64.3IU/ml(&amp;lt;5). MRI of the left thigh revealed an area of diabetic myonecrosis, measuring 11cm. He was treated with continuous insulin infusion. On hospital day 3, after resolution of the anion gap metabolic acidosis, transition was made to basal-bolus insulin. On hospital day 5, recurrent euglycemic DKA was diagnosed with bicarbonate 15mmol/L, anion gap 18mmol/L, beta-hydroxybutyrate 49.6mg/dl (&amp;lt;=3mg/dl), glucose 185mg/dl, glucosuria (4+) and ketonuria (4+). Continuous insulin infusion was restarted. On hospital day 8, transition was made to subcutaneous insulin. Diabetic myonecrosis was initially managed conservatively with analgesics, aspirin, and physical therapy. Due to worsening leukocytosis on hospital day 13, Ceftriaxone was started and surgical debridement was performed, revealing a loculated abscess within necrotic muscle. Empagliflozin was discontinued at discharge. Discussion: The risk of euglycemic DKA with SGLT2i use is increased in patients with T1DM and decreased oral intake, and insults like trauma or surgery as seen in this patient. Although the half-life of empagliflozin is 12 to 14 hours, there have been case reports of persistent or recurrent euglycemic DKA for 7-12 days from the time of last dose. The continued glucosuria and ketonuria in this patient with serum glucose levels below the renal threshold confirmed the recurrence. Diabetic myonecrosis usually affects the muscles of the proximal lower extremities and is seen in patients with poorly controlled diabetes with microvascular complications, between one and two decades after diagnosis, as in this patient. Conclusion: A high index of suspicion for recurrent euglycemic DKA must be maintained in patients who have new or persistent high anion gap metabolic acidosis until 2 weeks from last dose of SGLT2 inhibitor. Diabetic myonecrosis, especially if complicated by abscess formation, may require surgical intervention. Presentation: 6/1/2024

6853 A Curious Case of MACS

Abstract Disclosure: M. Dillon: None. A. Syeda: None. V. Kantorovich: None. Introduction: Mild autonomous cortisol secretion (MACS) is characterized by biochemical evidence of mild hypercortisolemia inducing metabolic comorbidities without any obvious phenotypic stigmata of Cushing’s syndrome (CS). This case highlights the challenges faced in the diagnosis and management of MACS. Case: A 76-year-old female with past medical history of class II obesity (BMI 31.83 kg/m2), type 2 diabetes mellitus, hypertension, hyperlipidemia, osteoporosis and chronic kidney disease stage IIIb was diagnosed with MACS after an overnight 1 mg dexamethasone suppression test (DST) showed unsuppressed 8 AM cortisol of 2.4 mcg/dL (&amp;lt;1.8 mcg/dL). Dexamethasone level was appropriate at 355 ng/dL (180-550 ng/dL), ACTH was &amp;lt;5 pg/mL (6-50 pg/mL) and DHEA-S was normal. Late night salivary cortisol (LNSC) levels were elevated to 0.12 mcg/dL (&amp;lt; 0.09 mcg/dL). The 24-hour urine cortisol level was normal. Baseline 8 AM cortisol level was 17 mcg/dL and ACTH was 19 pg/mL. Abdominal CT scan showed a 1 cm left adrenal nodule of 25 HU density and a normal right adrenal with no atrophy. Phaeochromocytoma and primary hyperaldosteronism work up was negative. She started on Mifepristone 300 mg daily and titrated up to 600 mg daily. She presented to our institution one month later with 1 week of nausea, vomiting and muscle weakness. Laboratory studies revealed acute kidney injury with creatinine of 6.69 mg/dL (baseline Cr 1.5 mg/dL) and rhabdomyolysis with creatinine kinase level of 12,819 U/L (24-173 U/L) and urine myoglobin level of 888 ng/mL (0-13 ng/mL). It was evident that her catastrophic presentation was from development of adrenal insufficiency in the setting of Mifepristone glucocorticoid receptor blockade. The drug was discontinued immediately. She was treated with intravenous hydration and intermittent diuretics. Over 10 days, her clinical status gradually improved and creatinine decreased to baseline levels. Discussion: MACS is a challenging diagnosis as cortisol levels are affected by several variables including obesity, drugs, and poorly controlled diabetes. Hence, a meticulous evaluation is mandated before confirming the diagnosis. Our patient’s baseline cortisol and ACTH levels were normal, and her DST and LNSC levels were mildly elevated. Unilateral cortisol producing adenoma causes contralateral gland atrophy due to suppressed ACTH. This was not evident in our patient, thus making the diagnosis questionable. Adrenalectomy is the treatment of choice in MACS with adrenal adenoma. Off label medical management with Mifepristone, a glucocorticoid receptor antagonist, is being pursued in select cases and was trialed due to our patient's age and surgical risk. Mifepristone is approved for the treatment of hyperglycemia due to CS. The data supporting its use in MACS is sparse. Therefore, it is important to be aware of associated risks of Mifepristone when advising patients. Presentation: 6/3/2024

Electrochemical immunosensor based on gold nanoparticles for the detection of creatine kinase as a cardiac marker

This study presents the development of an electrochemical immunosensor utilizing gold nanoparticles for the detection of creatine kinase (CK), a crucial cardiac marker. Gold nanoparticles with an average diameter of 18.3 ± 2.1 nm were synthesized and characterized, exhibiting a characteristic surface plasmon resonance peak at 520 nm. The construction of the immunosensor was observed through cyclic voltammetry and electrochemical impedance spectroscopy, showing notable alterations in electron transfer rates during each step of the assembly process. Optimal performance was achieved at pH 7.4, with an antibody concentration of 100 μg/mL and an incubation time of 45 minutes. The sensor demonstrated a sensitivity of 152.6 Ω/(ng/mL) and maintained its response in the presence of common interfering substances, with maximum signal deviation of 7.2 %. Testing with spiked human serum samples yielded recovery rates between 96.5 % and 103.8 %. Comparison with ELISA using clinical samples further validated the sensor's accuracy. This AuNP-based immunosensor offers a promising platform for rapid and sensitive CK detection in cardiac health assessment.

LncRNA MALAT1 to Enhance Pyroptosis in Viral Myocarditis Through UPF1-Mediated SIRT6 mRNA Decay and Wnt-β-Catenin Signal Pathway.

Viral myocarditis (VMC) is an inflammatory disease of the myocardium caused by cardioviral infection, especially coxsackievirus B3 (CVB3), and is a major contributor to acute heart failure and sudden cardiac death in children and adolescents. LncRNA MALAT1 knockdown reportedly inhibits the differentiation of Th17 cells to attenuate CVB3-induced VMC in mice. Moreover, long non-coding RNAs (lncRNAs) interact with RNA-binding proteins (RBPs) to regulate UPF1-mediated mRNA decay. However, it remains unclear whether MALAT1 can bind to UPF1 to mediate the mRNA decay of its target genes in VMC. Herein, we aimed to explore the effect of lncRNA MALAT1 on UPF1-mediated SIRT6 mRNA decay in VMC using in vivo and in vitro experiments. CVB3-infected BABL/C mice were used as VMC models, and MALAT1 interfering adenovirus was injected to achieve MALAT1 knockdown. The heart function of the VMC mice was assessed using echocardiography. Pathological changes in myocardial tissues were assessed after hematoxylin-eosin staining. Myocardial injury and inflammation were evaluated by measuring creatine kinase isoenzyme B, cardiac troponin T, interleukin (IL)-1β, and IL-18. TUNEL staining was performed to assess apoptosis in myocardial tissues. In vitro experiments were performed using H9c2 cells after transfection and CVB3 infection. The lactic dehydrogenase release, caspase-1 activity, and IL-1β and IL-18 levels in the cellular supernatant were detected. Western blotting was performed to determine the expression of pyroptosis-related proteins (GSDMD-N, NLRP3, ASC, and Cleaved-Caspase-1) and Wnt/β-catenin signal pathway-related proteins (Wnt1, β-catenin, and p-GSK-3β). RNA immunoprecipitation and RNA stability assays assessed the relationship between MALAT1, UPF1, and SIRT6. CVB3-infected mice and H9c2 cells exhibited elevated MALAT1 and reduced SIRT6 expression. MALAT1 knockdown or SIRT6 overexpression suppressed inflammation and pyroptosis and inhibited the activation of the Wnt/β-catenin signal pathway in myocardial tissues and cells. MALAT1 enhanced the enrichment of SIRT6 mRNA by UPF1 and disturbed the stability of SIRT6 mRNA to promote the development of VMC. MALAT1 can bind UPF1 to mediate SIRT6 mRNA decay and activate the Wnt/β-catenin signal pathway in VMC.

Ursolic Acid Restores Redox Homeostasis and Pro-inflammatory Cytokine Production in Denervation-Induced Skeletal Muscle Atrophy.

Skeletal muscle (SkM) atrophy results from metabolic disorders causing body and muscle mass loss, affecting morbidity and mortality. Increased oxidative stress, inflammation, and poor prognosis are the leading causes of involuntary weight loss. Ursolic acid (UA), known for its antioxidant and anti-inflammatory properties, can potentially reduce oxidative stress and inflammation in muscles, but its effects on muscle mass regulation are still unknown. Therefore, the present study investigated the medicinal efficacy of UA and its mode of action against the murine model of SkM atrophy over 7days of UA supplementation. Denervation-induced SkM atrophy significantly impacts overall body weight and the weight of individual muscles (p < 0.05). However, supplementation with UA can effectively counteract these effects by promoting the synthesis of the slow-myosin heavy chain, thereby restoring body weight and myotube diameter. Moreover, UA also plays a crucial role in reducing the production levels of reactive oxygen species (ROS), lipid peroxidation (LPO), and caspase-3-like activity in atrophied muscles. UA also prevents the leakage of creatine kinase (CK) through the upregulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) expression. Furthermore, the results obtained from qRT-PCR demonstrated a significant decrease in the levels of pro-inflammatory markers, namely IL-1β, IL-6, TNF-α, and TWEAK, up to four-fold after the third day of the UA intervention. UA also upregulated PGC-1α, Bcl2, and p-Aktser473 expression towards the regulation of redox homeostasis.