Elevated Creatine Kinase Research Articles

Safety and Efficacy of Upadacitinib in Crohn's Disease: An Updated Systematic Review.

Crohn's disease (CD) is a chronic inflammatory bowel disease that significantly impacts patient quality of life. This systematic review evaluates the safety and efficacy of upadacitinib, a selective Janus kinase (JAK) inhibitor, in the treatment of CD. A comprehensive literature search was conducted across multiple databases, yielding seven studies published between 2020 and 2024, encompassing 1,481 patients. The review includes randomized controlled trials, post hoc analyses of phase 3 trials, and observational studies. Findings consistently demonstrate upadacitinib's superiority over placebo in inducing and maintaining clinical remission, achieving endoscopic response, and normalizing inflammatory markers. Notably, upadacitinib showed rapid symptom relief, with clinical remission observed as early as five to six days after treatment initiation. Efficacy was observed across various patient populations, including those with prior biologic failure. Long-term studies indicated sustained clinical and endoscopic improvements, with remission rates maintained for up to 30 months. Upadacitinib also demonstrated effectiveness in real-world, treatment-refractory cohorts. Safety profiles were generally consistent with those of other JAK inhibitors. Common adverse events included infections, particularly herpes zoster, and laboratory abnormalities such as neutropenia and elevated creatine kinase. Serious adverse events were infrequent, although careful monitoring is warranted. This review suggests that upadacitinib is a promising treatment option for moderate to severe CD, offering rapid and sustained efficacy with an acceptable safety profile.

McArdle's Disease: A Differential Diagnosis of Metabolic Myopathies.

McArdle's disease, also known as glycogen storage disease type V or McArdle syndrome, is a pure muscle myopathy with an autosomal recessive inheritance pattern. It is caused by mutations in the gene that encodes muscle phosphorylase. Symptoms typically begin in late adolescence or early adulthood, presenting as exercise intolerance. This review focuses on the diagnosis of McArdle's disease, initially manifesting as a clinical picture of rhabdomyolysis in an 18-year-old male patient with a history of minor thalassemia who had been followed in pediatric consultation since age three for failure to thrive. After excluding common causes such as alcohol consumption, drug use, traumatic muscle compression, and other conditions, the diagnosis of McArdle's disease was considered. The diagnosis was supported by laboratory tests showing myoglobinuria and elevated creatine kinase levels, as well as the absence of increased serum lactate following ischemic exercise. Genetic testing confirmed the presence of mutations in the PYGM gene, corroborating the diagnosis. Treatment includes administering a diet rich in slow-absorbing carbohydrates, regular low-intensity physical exercise, and, in some cases, supplementation with vitamin B6 and creatine. The prognosis is generally favorable with proper disease management, although vigorous exercise should be avoided to prevent complications such as severe muscle injury and rhabdomyolysis. Although McArdle's disease is a rare condition, it is likely underdiagnosed. Ideally, it should be considered in the differential diagnosis of rhabdomyolysis in all patients with symptoms of exercise intolerance and/or recurrent myoglobinuria.

Asymptomatic pediatric presentation of S-adenosylhomocysteine hydrolase deficiency.

S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive inborn error of metabolism affecting methylation by disrupting the methionine cycle. Its clinical spectrum spans from severe perinatal encephalomyopathy and liver failure to asymptomatic course in patients with isolated hypermethioninemia. We present two new cases of S-adenosylhomocysteine hydrolase deficiency from Pakistani origin clinically asymptomatic at presentation. Both siblings showed mild chronic liver failure and elevation of creatine kinase. The older patient presented at 6 years of age with isolated verbal processing difficulty and mild diffuse leukodystrophy, reversible 12 months after introduction of methionine dietary restriction. The patient showed subtle atrophy in the muscle MRI at the age of 7 years. S-adenosylhomocysteine hydrolase deficiency was confirmed with homozygous missense variant c.146G>A (p.Arg49His) in the AHCY gene, a genotype previously reported in Pakistani patients with mild presentation. Dietary methionine restriction decreased plasma methionine but not plasma S-adenosylhomocysteine and S-adenosylmethionine. This work expands the mild spectrum of S-adenosylhomocysteine hydrolase deficiency with no noticeable clinical symptoms in children, highlighting a specific hotspot variant from South Asia. This mild form of the disease is likely underdiagnosed and raises the question of therapeutic management to prevent long-term complications documented in the literature, such as hepatocellular carcinoma and myopathy in early adulthood.

EXTRAHEPATIC MANIFESTATIONS IN PATIENTS WITH ACUTE HEPATITIS E – PAZARDZHIK, BULGARIA 2014 – 2022

BACKGROUND: Hepatitis E is a global health issue, only partially understood. Bulgarian record started in 2019 and data is not sufficient. AIM: This research aims to analyze extrahepatic manifestation of acute hepatitis E in patients with hepatitis E from Pazardzhik region, between 2014 – 2022. MATERIALS AND METHODS: The analysis includes 247 patients with acute hepatitis E, treated at the Department of Infectious Diseases of Pazardzhik Multiprofile Hospital for Active Treatment, Bulgaria between 2014 – 2022. The methodology includes clinical observation, laboratory tests and medical imaging. The diagnosis was established by serological /ELISA for anti-HEV IgM, IgG detection/and molecular-biological tests /RT-PCR for HEV RNA detection/. RESULTS: We observed extrahepatic manifestations in 19% (47/247) of the cases. In 60% (28/47) comorbidities were present, and 9% (4/47) were with underlying acute/chronic coinfection with another hepatotropic virus. Thrombocytopenia was found in 83% (39/47) of the patients; asymptomatic creatine kinase elevation – in 13% (6/47), acute pancreatitis – in 9% (4/47), transitory renal impairent – in 6% (3/47); 2% (1/47) had Guillain-Barré syndrome (GBS), 2% (1/47) – arrhythmia and 13% (6/47) – multiorgan involvement. While 91% (43/47) of the patients recovered, in 9% (4/47) the outcome was fatal. CONCLUSION: Extrahepatic manifestations might prevail, potentially delaying diagnosis of HEV-infection. Symptoms associated with comorbidities might also impede the final diagnosis. A diagnostic algorithm is needed to enhance the accurate diagnosis of HEV in patients with dubious symptoms.

Benefits of Early Versus Late Initiation of Intravenous Immunoglobulin in the Treatment of Patients With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Immune-Mediated Necrotizing Myopathy.

No clinical trials have been conducted to establish optimal and effective treatment in patients with immune-mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti-HMGCR IMNM. We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti-HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti-HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti-HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti-HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria. Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment (P < 0.001). At disease onset, cohorts had a comparable serum CK (P > 0.999), but patients with delayed treatment had an expected lower serum CK (P = 0.016) at the 0-month time point. At the 0-month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12-month intervals (P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment (P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did. Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti-HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long-term disability.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

Rare skin color changes in an acute pancreatitis patient undergoing maintenance hemodialysis

BackgroundSkin conditions are common in patients on maintenance hemodialysis and those with pancreatitis. However, there is a lack of research on dermatological issues in patients who have both hemodialysis and pancreatitis concurrently.Case presentationA 62-year-old male patient with a 4-year history of maintenance hemodialysis (MHD) presented with pain and was diagnosed with acute pancreatitis and gallbladder stones. Markedly elevated blood amylase, creatine kinase, and myoglobin were noted, alongside a purplish-red skin discoloration. Treatment included inhibition of digestive fluid secretion, anti-infection measures, blood purification, fasting, rehydration, and symptomatic care. Notably, continuous renal replacement therapy (CRRT) combined with hemoperfusion (HP) was employed. The patient’s dialysis effluent initially appeared red. Upon examination of the patient’s peripheral blood smear, red blood cell debris was not observed. The dialysis effluent (on Day 0) was analyzed, revealing no hemoglobin (0 g/L) but an elevated myoglobin concentration of 80.4 U/L. After the therapeutic intervention, the indicators, including the blood amylase, C-reactive protein, total bilirubin, creatine kinase, and myoglobin were improved. The patient experienced resolution of sternal and upper abdominal pain within two days. After four consecutive days of CRRT and HP treatment, the skin color returned to normal, alongside improved clarity of the dialysis effluent. Subsequently, the patient’s method of blood purification was reverted to conventional hemodialysis. On the eighth day of hospitalization, the patient resumed normal diet and was discharged.ConclusionsIn the case of the current patient with acute pancreatitis undergoing MHD, it is noteworthy to report the observation of a unique purplish-red skin discoloration. This phenomenon may be attributable to inflammation resulting from acute pancreatitis, and the retention of myoglobin within the body.

Lower extremity pain and/or numbness after laparoscopic surgery and robot-assisted surgery in the lithotomy position combined with the Trendelenburg position.

The purpose of this study was to investigate the incidence and risk factors of lower extremity pain and/or numbness after laparoscopic colorectal surgery and robot-assisted laparoscopic radical prostatectomy in the lithotomy position combined with the Trendelenburg position. The relationship between creatine kinase (CK) levels and lower extremity pain and/or numbness was also investigated. We retrospectively reviewed adult patients who underwent laparoscopic colorectal surgery and robot-assisted laparoscopic radical prostatectomy in the lithotomy position combined with the Trendelenburg position between May 2015 and April 2020. Logistic regression analysis was used to identify risk factors of lower extremity pain and/or numbness. Preoperative and postoperative CK levels were compared in patients with and those without lower extremity pain and/or numbness. Among 940 patients, 1.9% experienced lower extremity pain and/or numbness postoperatively. The incidences of lower extremity pain and/or numbness after laparoscopic colorectal surgery and after robot-assisted laparoscopic radical prostatectomy were 1.7% and 2.1%, respectively. Multivariate logistic regression analysis revealed that only duration of surgery > 4h (odds ratio = 3.144, 95% CI: 1.102-8.969, p = 0.032) was a significant predictor of lower extremity pain and/or numbness. Postoperative median CK level in patients with lower extremity pain and/or numbness was significantly higher than that in patients without lower extremity pain and/or numbness. The incidence of lower extremity pain and/or numbness after laparoscopic colorectal surgery was comparable to that after robot-assisted laparoscopic radical prostatectomy. Prolonged duration of surgery contributed to lower extremity pain and/or numbness. Significantly elevated CK levels in patients with lower extremity pain and/or numbness suggest the involvement of muscle injury in these symptoms.

Assessing risk factors for elevated creatine kinase levels as an indicator of compartment syndrome following laparoscopic or robot-assisted colorectal cancer surgery in the lithotomy-trendelenburg position

BackgroundWell-leg compartment syndrome (WLCS) can occur due to compression and lower limb circulation disturbances caused by the surgical position during the procedure. Although rare, with an incidence of 1 in 3500 surgeries performed in the lithotomy position, it can lead to serious complications. Therefore, prevention and early diagnosis are critical. Symptoms of WLCS, such as leg pain, swelling, paresthesia, and serum creatine kinase (CK) levels are useful for diagnosis. This study aimed to investigate the risk factors for postoperative CK elevation in laparoscopic or robot-assisted colorectal cancer surgery performed in the lithotomy-Trendelenburg position.MethodsPostoperative CK levels were measured in 178 patients who underwent laparoscopic or robot-assisted colorectal cancer surgery between February 2022 and March 2023. We compared patient backgrounds, short-term outcomes, and thigh/calf circumferences between patients with CK levels ≥ 250 (n = 62) and those with CK levels < 250 (n = 116). We investigated risk factors for elevated CK levels using both univariate and multivariate analyses.ResultsFour patients with CK levels of 22405 U/L, 4685 U/L, 4050 U/L, and 3824 U/L reported symptoms, which improved with conservative treatment. The following independent prognostic factors were identified by multivariate analysis: male sex (odds ratio [OR], 4.403; 95% CI, 1.960 to 9.892), rectal surgery (OR, 2.779; 95% CI, 1.249 to 6.184), continuous head-down position duration ≥ 180 min (OR, 3.523; 95% CI, 1.552 to 7.997), and preoperative calf circumference ≥ 33 cm (OR, 2.482; 95% CI, 1.154 to 5.339).ConclusionsRisk factors for CK elevation after colorectal cancer surgery in the lithotomy position include male sex, rectal surgery, an extended continuous head-down position without position changes, and a larger preoperative calf circumference. This study highlights the potential importance of intraoperative position changes every 3 h for preventing elevated CK levels, although the preventive effect was not specifically examined.

Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.

Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD. The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 genes implicated in LGMD. The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, and COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD. The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.

Clinical features and genetic analysis of 5 cases of infantile-type glycogen storage disease type II: Case reports.

Clinical and genetic mutation analysis was performed on 5 infantile glycogen storage disease type II children in Chinese mainland. Clinical data of 5 children with infantile-type glycogen storage disease type II due to the acidic α-glucosidase (GAA) gene variants diagnosed and treated at Hebei Provincial Children's Hospital from January 2018 to April 2020 were retrospectively analyzed. Among the 5 cases, 1 was female and 4 were male, and the age at first diagnosis was from 2 months to 7 months. The first symptoms of all 5 cases showed progressive muscle weakness, hypotonia, and motor developmental backwardness, and all of them had abnormally elevated creatine kinase, and the echocardiograms suggested different degrees of myocardial hypertrophy, with ejection fractions ranging from 44% to 67%. Analysis of GAA gene variations: all 5 cases were compound heterozygous, and a total of 12 variant loci were detected, of which c.2024_2026delACA, c.2853G > A, c.1124G > T, c.574G > A, c.2509C > T, and c.2013G > A were new mutations that had not been reported. All 5 children died before 1 year of age, and the age of death ranged from 7 months to 11.5 months, with a mean survival time of 9.8 months. Peripheral blood GAA gene testing and alpha-glucosidase enzyme activity testing is an effective method for diagnosing this disease.

Efficacy and safety of pralsetinib in patients with RET fusion positive non–small cell lung cancer: An observational real world study

BackgroundPralsetinib, a selective RET targeted tyrosine kinase inhibitor (TKI), has been approved for treating locally advanced or metastatic RET fusion-positive NSCLC in adults who have previously received platinum-based chemotherapy in China. MethodsIn this retrospective analysis conducted at Hunan Cancer Hospital in China, we examined 36 patients with advanced NSCLC with RET fusion, who were treated with pralsetinib between January 2021 and December 2023. The study focused on assessing the efficacy (Progression-free survival (PFS) and overall survival (OS)) and safety profile of pralsetinib in these patients. Statistical analyses were conducted using SPSS version 20.0, with a significance level set at p < 0.05. ResultsThe results revealed that pralsetinib exhibited significant activity in this patient cohort. Kaplan-Meier survival analysis indicated a median PFS of 10.7 months and a median OS of 21.2 months. The overall response rate(ORR) and disease control rate (DCR) was 55.6 % and 72.2 %, respectively. Pralsetinib was generally well tolerated, with most adverse events being mild to moderate (grades 1–2). The most common serious adverse events (≥grade 3) observed were lymphopenia (13.9 %), hypertension (11.1 %), leukopenia (8.3 %), neutropenia (8.3 %), and creatine kinase elevation (8.3 %). ConclusionPralsetinib demonstrated promising activity in patients with advanced NSCLC harboring RET fusion with a favorable safety profile.

Diagnostic Value of Whole-Body MRI in Pediatric Patients with Suspected Rheumatic Diseases.

Background and Objectives: The diagnosis of rheumatic diseases in children is challenging and requires the use of advanced imaging examinations such as whole-body magnetic resonance imaging (MRI). Whole-body MRI allows visualization of bone marrow edema (BME), muscle edema, joint effusion and changes in the soft tissues surrounding the joints. The aim of this study was to collect and compare whole-body MRI findings, laboratory results and clinical manifestations of pediatric patients with suspected rheumatic disease. Materials and methods: In this retrospective single-center study, 33 patients who underwent whole-body MRI were included. Their age ranged from 9 to 17 years, and 24 (72.73%) of the patients were female. Patients were diagnosed as follows: juvenile idiopathic arthritis (27.27%), juvenile idiopathic inflammatory myopathies (21.21%), chronic nonbacterial osteomyelitis (21.21%) and other medical conditions (30.30%), such as arthritis associated with infection, scleroderma, Takayasu arteritis, polyarteritis nodosa and joint damage. Results: The most common symptom reported by 26 (79.79%) patients was pain. On physical examination, the limitation of joint mobility was examined in 17 (51.51%), swelling of the joints was observed in 12 (36.36%) patients and decreased muscle strength was noticed in 11 (33.33%) patients. An increase in the C-reactive protein (12%), erythrocyte sedimentation rate (9%), leukocyte count (9%) and creatine kinase (CK) (18%) was observed. Whole-body MRI revealed myositis (30%), joint effusion (27%) and BME (24%). The statistical analysis showed a significant relationship between myositis and the elevated CK level (p < 0.05). Conclusions: The most common symptom in the studied population was pain, while the limitation of joint mobility was found in more than half of patients. Myositis was the most commonly imaged lesion on the whole-body MRI and it was related to an increase in the CK level.

An International Retrospective Early Natural History Study of LAMA2-Related Dystrophies.

LAMA2-related dystrophies (LAMA2-RDs) represent one of the most common forms of congenital muscular dystrophy and have historically been classified into two subtypes: complete or partial deficiency of laminin-211 (merosin). Patients with LAMA2-RD with the typical congenital phenotype manifest severe muscle weakness, delayed motor milestones, joint contractures, failure to thrive, and progressive respiratory insufficiency. While a comprehensive prospective natural history study has been performed in LAMA2-RD patients over 5 years of age, the early natural history of patients with LAMA2-RD 5 years and younger has not been comprehensively characterized. We extracted retrospective data for patients with LAMA2-RD ages birth through 5 years via the Congenital Muscle Disease International Registry (CMDIR). We analyzed the data using a phenotypic classification based on maximal motor milestones to divide patients into two phenotypic groups: "Sit" for those patients who attained that ability to remain seated and "Walk" for those patients who attained the ability to walk independently by 3.5 years of age. Sixty patients with LAMA2-RD from 10 countries fulfilled the inclusion criteria. Twenty-four patients had initiated non-invasive ventilation by age 5 years. Hospitalizations during the first years of life were often related to respiratory insufficiency. Feeding/nutritional difficulties and orthopedic issues were commonly reported. Significant elevations of creatine kinase (CK) observed during the neonatal period declined rapidly within the first few months of life. This is the largest international retrospective early natural history study of LAMA2-RD to date, contributing essential data for understanding early clinical findings in LAMA2-RD which, along with the data being collected in international, prospective early natural history studies, will help to establish clinical trial readiness. Our proposed nomenclature of LAMA2-RD1 for patients who attain the ability to sit (remain seated) and LAMA2-RD2 for patients who attain the ability to walk independently is aimed at further improving LAMA2-RD classification.

Strategies to Address Statin Medication Intolerance Among Patients at Risk of Cardiovascular Disease Identified Through Electronic Health Records: A Literature Review and Pooled Analysis.

Statins are a group of medications that lower lipid and are used for primary and secondary prevention of cardiovascular diseases (CVD). Patients can either be partially (15%) or completely (5%) intolerant to statins. Symptoms of statin intolerance can include muscle aches (myalgia), weakness, cramps, myopathy, diabetes mellitus, and elevated creatine kinase levels. Decreasing statin intolerance also improves statin adherence, which in turn results in lower number of CVD events among patients. Studies on statin intolerance is often embedded within studies of statin adherence. However, relevant data can be obtained from digital health systems. This preliminary literature review looks at studies from the past 10 years to identify and determine the effectiveness of strategies to address statin intolerance. The NLA definition for statin intolerance was used in this review. The initial search results on EMBASE, PubMed, SCOPUS, and CINAHL showed 91 articles and applying the inclusion and exclusion criteria, four articles were used in this review and pooled analysis. The study patients were identified through electronic health records. The pooled analysis was done using the Metafor package in R, applying a random-effect model to estimate pooled effect size. The findings suggest that using fixed dose combination therapy and switching from a lipophilic statin to a hydrophilic statin, while correcting metabolic abnormalities, or initiating evolocumab alongside statin can address statin intolerance. The overall relative risk (RR) was 0.40 (95% CI, 0.09 to 1.70) with I2 90%, and the overall odds ratio (OR) was 0.11 (95% CI, 0.01 to 1.59) with I2 94%, suggesting that the interventions work well in addressing statin intolerance. Since statin intolerance is has a vast range of effects, further research works may be done on exploring the possibility of using digital health systems to identify and provide targeted interventions to patients.

Chamomile Extract Reduces Cardiac Toxicity in Female Mice with Ehrlich Solid Carcinoma.

Cancer is the most serious disorder that may affect a person and is also the leading cause of mortality. Worldwide, breast cancer continues to be the leading cause of cancer-related deaths in women. The popularity of treating diseases using alternative and complementary medicines has increased in recent decades; many of these are derived from plants. Chamomile has a beneficial effect in treating many diseases, there for the purpose of this work is to study how chamomile protect against cardiac damage and toxicity brought on by Ehrlich solid tumor (EST) in adult female mice. 40 female mice were distributed in 4 groups (control, chamomile, EST, EST+chamomile). The research results indicated that EST caused significant alterations in cardiac function and structure. EST induced a significant elevation in serum creatine kinase (CK), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and myoglobin (MB), potassium, chloride ions, cholesterol, triglycerides, low-density lipoprotein (LDL), cardiac tissue damage, apoptotic P53 and Caspase 3 expressions while levels of sodium ions and high-density lipoprotein (HDL) were significantly decreased. Treatments of EST with chamomile improved the biochemical, histopathological, and Immunohistochemical alterations. This suggests that chamomile may be useful as an adjuvant for the treatment and prevention of cardiac toxicity.

A Rare Case of Late Onset-Pompe’s Disease: Presented as Heart Failure

Pompe disease is a hereditary lysosomal storage disorder characterized by a deficiency in the acid alpha-glucosidase (GAA) enzyme, leading to glycogen accumulation in muscle and neurons. Clinical manifestations vary from severe infantile-onset with hypertrophic cardiomyopathy and early mortality due to respiratory insufficiency to late-onset with proximal muscle weakness, gross motor delay, and progressive respiratory insufficiency. A case of an 11-year-old boy who reported to the pediatric emergency department with a nine-year history of progressive muscle weakness and a one-month history of anemia symptoms (easy fatigue, shortness of breath, pale appearance) and heart failure (orthopnea, dyspnea). His family history included consanguineous marriages and similar conditions in his brother and maternal uncle. On examination, he appeared pale, malnourished, and exhibited signs of respiratory distress and tachypnea. His cardiovascular examination revealed apex beat displacement, elevated JVP, bilateral pedal edema, mild ascites, positive hepatojugular reflux, and systolic murmurs. Respiratory examination indicated bilateral crepitation and wheezes. Musculoskeletal examination showed decreased muscle mass and power, especially in proximal muscles. Abdominal examination revealed hepatosplenomegaly and mild ascites. Radiological findings included an enlarged cardiac shadow with pleural effusion and bilateral radio-opaque shadows on chest x-ray, while echocardiography showed impaired left ventricular systolic function with mild to moderate mitral and tricuspid regurgitation. Laboratory tests indicated elevated aspartate aminotransferase, LDH, and creatine kinase levels, along with normocytic, normochromic anemia. Muscle biopsy from the hamstring revealed PAS stain positive granules. These clinical, radiological, and laboratory findings strongly suggest late-onset Pompe disease, marking this as potentially the second reported case in Pakistan.

Base excess is superior to creatinine in predicting haemodialysis: A multicenter study conducted Kahramanmaraş earthquake victims

PurposeThis study had two main goals: to determine which rhabdomyolysis patients need haemodialysis; and to highlight the significance of blood gas parameters, particularly base excess, as predictors of the need for haemodialysis. MethodA total of 270 patients were included in this multicentre, retrospective study. Among the patients who were transferred in from the earthquake region and developed rhabdomyolysis, those with creatine kinase (CK) values >1000 U/L were included in our study. The need for renal replacement in these patients was determined via laboratory tests, urine output monitoring and clinical follow-up. FindingsA total of 270 patients were included in our study. Univariate and multivariate regression analyses of laboratory parameters were performed to identify predictors of HD treatment. According to the univariate regression analysis, BE, HCO3, creatinine, CK, lactate, alanine transaminase (ALT) and aspartate transaminase (AST) levels were found to be significantly associated with receiving HD treatment. According to multivariate regression analysis, only BE (p = 0.003) was found to be a significant predictor of HD treatment. ROC analysis revealed that the optimal cutoff value for BE was −2.6; at this value, the sensitivity and specificity of BE for predicting HD treatment were 89% and 77.1%, respectively (AUC: 0.912; 95% CI: 0.872–0.943; p < 0.001). ConclusionBase excess is an effective predictor of the need for haemodialysis in patients with crush-related injuries that cause rhabdomyolysis and in patients who develop acute renal failure due to elevated CK.

Comparative Analysis of Tentacle Extract and Nematocyst Venom: Toxicity, Mechanism, and Potential Intervention in the Giant Jellyfish Nemopilema nomurai.

The giant jellyfish Nemopilema nomurai sting can cause local and systemic reactions; however, comparative analysis of the tentacle extract (TE) and nematocyst venom extract (NV), and its toxicity, mechanism, and potential intervention are still limited. This study compared venom from TE and NV for their composition, toxicity, and efficacy in vitro and in vivo used RAW264.7 cells and ICR mice. A total of 239 and 225 toxin proteins were identified in TE and NV by proteomics, respectively. Pathological analysis revealed that TE and NV caused heart and liver damage through apoptosis, necrosis, and inflammation, while TE exhibited higher toxicity ex vivo and in vivo. Biochemical markers indicated TE and NV elevated creatine kinase, lactatedehydrogenase, and aspartate aminotransferase, with the TE group showing a more significant increase. Transcriptomics and Western blotting indicated both venoms increased cytokines expression and MAPK signaling pathways. Additionally, 1 mg/kg PACOCF3 (the phospholipase A2 inhibitor) improved survival from 16.7% to 75% in mice. Our results indicate that different extraction methods impact venom activities, tentacle autolysis preserves toxin proteins and their toxicity, and PACOCF3 is a potential antidote, which establishes a good extraction method of jellyfish venom, expands our understanding of jellyfish toxicity, mechanism, and provides a promising intervention.

Compound Heterozygous Variants of GOSR2 Associated With Congenital Muscular Dystrophy and Progressive Myoclonus Epilepsy: A Case Report.

The GOSR2 gene is a Golgi vesicle transport gene that encodes for the Golgi SNAP receptor complex member 2 protein. This protein mediates transport between the medial and trans-Golgi compartments. The homozygous missense variant in the GOSR2 gene, c.430G>T, has been associated with progressive myoclonus epilepsy (PME). There have been reports suggesting that compound heterozygous GOSR2 variants are associated with the congenital muscular dystrophy (CMD) phenotype. In this article, we report a pediatric case with congenital hypotonia, motor delay, elevated creatine kinase, and abnormal muscle biopsy consistent with CMD who subsequently developed PME. Whole-exome sequencing identified pathogenic compound heterozygous variants in the GOSR2 gene, one of which was the previously described PME-related c.430G>T(p.Gly144Trp), and a novel variant, c.22dup(p.Thr8fs). To our knowledge, this is a novel case of compound heterozygous variants in GOSR2 associated with both CMD and PME phenotypes. This case adds to the expanding clinical phenotype of GOSR2-related neurologic diseases.