Increased Creatine Kinase Research Articles

Twenty-Four Percent of Wildland Firefighters Reach Critical Levels of Serum Creatine Kinase During 80-Hour Critical Training.

Wildland firefighters (WLFFs) must undergo a 2-wk critical training (CT) period prior to deployment to the field. This stress may result in clinical risks, including severe muscle damage and rhabdomyolysis. We aimed to document the effects of WLFFs' CT on physiologic markers of muscle damage and soreness. Two interagency hotshot crews (n=25) were followed during spring 2022 for 80 h of training. Activity counts as well as records of upper-body (US) and lower-body (LS) muscle soreness were collected daily. Body weight (BW) and skinfold measurements were recorded on Day 1 (D1) and D11 to estimate body fat (BF) and lean body weight (LBW). Blood was collected on D1 and D11 to measure muscle and liver damage markers. Critical training resulted in significant elevations in creatine kinase (CK) (216.9±57.4 U/L vs 5166.4±1927.8 U/L, P=0.017) and lactate dehydrogenase (LDH) (175.5±4.0 IU/L vs 340.0±42.6 IU/L, P=0.001) despite no significant changes in BW, BF, LBW, cortisol, or testosterone. Main effects of time were seen in US and LS, peaking on D11 (US: 5.2±0.4 cm, P<0.001; LS: 5.5±0.4 cm, P<0.001). Those who spent the most minutes with activity counts of >1500 counts/min showed the greatest increase in CK and LDH. These data suggest that WLFFs undergo significant physiologic stressors, resulting in muscle soreness and damage during CT, with 6 of the 25 subjects reaching critical levels of serum CK. It appears that much of the muscle damage and soreness occurred because of unaccustomed WLFF job-specific tasks.

Effects of Tofacitinib on Muscle Remodeling in Experimental Rheumatoid Sarcopenia.

Sarcopenia is a frequent comorbidity of rheumatoid arthritis (RA). Clinical trials have shown that JAK inhibitors (JAKi) produce an asymptomatic increase in serum creatine kinase (CK) in RA, suggesting an impact on muscle. We evaluated the effect of JAKi in muscle remodeling in an experimental RA model. Antigen-induced arthritis (experimental RA, e-RA) was performed in 14 rabbits. Seven rabbits received tofacitinib (TOFA, orally 10 mg/kg/day). Animals were euthanized one day after the last ovalbumin injection, and muscles were prepared for histology, RT-PCR, and WB. C-reactive protein (CRP) and Myostatin (MSTN) serum concentration were determined by ELISA. Creatine and creatine kinase (CK) were analyzed. An increase in body weight as well as tibialis anterior cross-sectional area and diameter was observed in e-RA+TOFA vs. e-RA. e-RA decreased type II fibers and increased the myonuclei number, with all reverted by TOFA. TOFA did not modify CRP levels, neither did MSTN. TOFA significantly reduced IL-6, atrogin-1, and MuRF-1 compared with e-RA. e-RA+TOFA showed higher CK and lower creatine levels compared with e-RA. No differences in PAX-7 were found, while TOFA prevented the increase in MyoD1 in e-RA. Our model reflects the features of rheumatoid sarcopenia in RA. JAKi increased muscle mass through attenuating IL-6/JAK/STAT activation, decreasing atrogenes, and restoring muscle differentiation markers. These data together with an increase in CK support the role of CK as a valuable marker of muscle gain following JAKi treatment.

Chlamydia psittaci pneumonia in Wuxi, China: retrospective analysis of 55 cases and predictors of severe disease.

More and more patients with community-acquired pneumonia have been detected with Chlamydia psittaci (C. psittaci) infected using metagenomic next-generation sequencing (mNGS). Previously, this was unheard of, and several patients presented with severe pneumonia and even required ECMO. We aimed to clarify the clinical characteristics of C. psittaci pneumonia and find out if there are any possible predictors of severe C. psittaci pneumonia. In this retrospective study, we included all confirmed cases of C. psittaci pneumonia in Wuxi. Epidemiological, clinical, and radiological features, as well as laboratory data, were collected and analyzed. We enrolled 55 patients with C. psittaci pneumonia, with 30 (54.5%) having a history of exposure to birds or their internal organs. 50 (90.9%) patients were diagnosed by mNGS. Patients with C. psittaci pneumonia had many complications, among which, that deserve sufficient attention from clinicians were vascular embolic events (3, 5.5%). High fever was the most common clinical manifestation (41, 74.5%). The majority of patients had a significant increase in neutrophils ratio, neutrophils to lymphocytes ratio (NLR), rapid c-reactive protein, creatine kinase (CK), and lactate dehydrogenase (LDH), as well as a decrease in lymphocytes ratio, albumin, serum sodium, serum potassium, and serum phosphorus. Chest computed tomography scans revealed unilateral pneumonia (70.9%), consolidation (87.3%), air bronchogram (76.4%), and ground-glass opacity (69.1%). The neutrophil ratio, NLR, LDH, and CK were all factors that could identify severe pneumonia. Both AUCs exceeded 0.8; the respective 95% CIs were 0.715-0.944, 0.710-0.963, 0.677-0.937, and 0.718-0.950; all p < 0.05 (0.01, 0.001, 0.007, 0.007 respectively). The ORs were 10.057, 9.750, 10.057, and 9.667, respectively; the 95% CIs were 2.643-38.276, 2.339-40.649, and 2.643-38.276, respectively; all p-values were less than 0.05 (0.001, 0.002, 0.001, 0.001 respectively). C. psittaci pneumonia is a very complex disease that changes all the time. Some patients showed severe pneumonia. Patients will have a poor prognosis if they are not treated promptly and effectively. We discovered that many clinical indicators were typical. Meanwhile, significant increases in neutrophil ratio, NLR, LDH, and CK predicted severe pneumonia. Timely detection of mNGS provided substantial help for clinical diagnosis and early treatment.

Clinical features and outcome of eight patients with Chlamydia psittaci pneumonia diagnosed by targeted next generation sequencing.

The clinical symptoms of Chlamydia psittaci pneumonia are still poorly understood. This study was designed to summarize the clinical features and outcome of eight C. psittaci pneumonia patients diagnosed by targeted next generation sequencing (tNGS). We included eight C. psittaci pneumonia patients admitted to our hospital from January 2021 to July 2022. The tNGS was performed to the samples collected from bronchoalveolar lavage fluid of each patient. Their clinical data were analysed, including baseline features, clinical symptoms, chest radiographic findings and laboratory examinations. The tNGS sequence number for C. psittaci was in a range of 10 to 1722. The radiographic characteristics were mainly featured by patchy consolidation shadows, ground-glass density shadows, air bronchogram and slight pleural effusion. Within 1-3days after hospitalization, most patients showed increased neutrophil ratio, C-reactive protein and erythrocyte sedimentation rate, and decreased lymphocyte count, total protein, albumin and prealbumin. Some patients showed increased glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase and lactate dehydrogenase levels. Three critically ill patients showed increased creatine kinase, creatine kinase isoenzyme and high-sensitivity troponin T (hs-TnT) levels. A poultry or bird contact history, typical flu-like symptoms, patchy consolidation, ground-glass density shadow and air bronchogram may contribute to the diagnosis and treatment of C. psittaci pneumonia. Increase in creatine kinase, creatine kinase isoenzyme and hs-TnT may indicate a severe condition. Moxifloxacin and minocycline were effective in the management of C. psittaci pneumonia.

V-ATPase V0 subunit activation mediates maduramicin-induced methuosis through blocking endolysosomal trafficking in vitro and in vivo.

Methuosis, a novel cell death phenotype, is characterized by accumulation of cytoplasmic vacuolization upon external stimulus. Methuosis plays a critical role in maduramicin-induced cardiotoxicity despite the underlying mechanism is largely unknown. Herein, we aimed to investigate the origin and intracellular trafficking of cytoplasmic vacuoles, as well as the molecular mechanism of methuosis caused by maduramicin (1μg/mL) in myocardial cells. H9c2 cells and broiler chicken were used and were exposed to maduramicin at doses of 1μg/mL in vitro and 5ppm-30ppm in vivo. Morphological observation and dextran-Alexa Fluor 488 tracer experiment showed that endosomal compartments swelling and excessive macropinocytosis contributed to madurdamcin-induced methuosis. Cell counting kit-8 assay and morphology indicated pharmacological inhibition of macropinocytosis largely prevent H9c2 cells from maduramicin-triggered methuosis. In addition, late endosomal marker Rab7 and lysosomal associated membrane protein 1 (LAMP1) increased in a time-dependent manner after maduramicin treatment, and the recycling endosome marker Rab11 and ADP-ribosylation factor 6 (Arf6) were decreased by maduramicin. Vacuolar-H+-ATPase (V-ATPase) was activated by maduramicin, and pharmacological inhibition and genetic knockdown V0 subunit of V-ATPase restore endosomal-lysosomal trafficking and prevent H9c2 cells methuosis. Animal experiment showed that severe cardiac injury included the increase of creatine kinase (CK) and creatine kinase-MB (CK-MB), and vacuolar degeneration resembled methuosis in vivo after maduramicin treatment. Taken together, these findings demonstrate that targeting the inhibition of V-ATPase V0 subunit will prevent myocardial cells methuosis by restoring endosomal-lysosomal trafficking.

BRAF–MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas

BackgroundCraniopharyngiomas, primary brain tumors of the pituitary–hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF–MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy.MethodsEligible patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease received the BRAF–MEK inhibitor combination vemurafenib–cobimetinib in 28-day cycles. The primary end point of this single-group, phase 2 study was objective response at 4 months as determined with the use of centrally determined volumetric data.ResultsOf the 16 patients in the study, 15 (94%; 95% confidence interval [CI], 70 to 100) had a durable objective partial response or better to therapy. The median reduction in the volume of the tumor was 91% (range, 68 to 99). The median follow-up was 22 months (95% CI, 19 to 30) and the median number of treatment cycles was 8. Progression-free survival was 87% (95% CI, 57 to 98) at 12 months and 58% (95% CI, 10 to 89) at 24 months. Three patients had disease progression during follow-up after therapy had been discontinued; none have died. The sole patient who did not have a response stopped treatment after 8 days owing to toxic effects. Grade 3 adverse events that were at least possibly related to treatment occurred in 12 patients, including rash in 6 patients. In 2 patients, grade 4 adverse events (hyperglycemia in 1 patient and increased creatine kinase levels in 1 patient) were reported; 3 patients discontinued treatment owing to adverse events.ConclusionsIn this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF–MEK inhibitor combination vemurafenib–cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.)

Extremely elevated creatine kinase associated with rhabdomyolysis-induced acute kidney injury in a patient with Huntington’s disease: a case report

BackgroundRhabdomyolysis-induced acute kidney injury is a serious condition that can progress to acute renal failure if not promptly identified and treated. Rhabdomyolysis occurs when serum creatine kinase levels approach > 1000 U/L (five times the normal upper limit). The chance of acute kidney injury increases as the levels of creatine kinase increase. Although Huntington’s disease is associated with muscle atrophy, elevated baseline creatine kinase levels in these patients have not been routinely reported.Case presentationA 31-year-old African American patient presented to the emergency department after he was found unconscious from a fall attributed to the progression of his Huntington’s disease. On admission, he had an extremely high creatine kinase level of 114,400 U/L and was treated with fluids, electrolyte balance, and dialysis. However, his condition progressed to acute renal failure and he later developed posterior reversible encephalopathy syndrome, requiring transfer to the intensive care unit with placement on continuous renal replacement therapy. Eventually, his kidney function recovered and he was discharged home with 24/7 care by his family for persistent impairments related to his Huntington’s disease.ConclusionsThis case report underscores the importance of promptly recognizing elevated creatine kinase levels in patients with Huntington’s disease due to the risk of developing rhabdomyolysis-induced acute kidney injury. If not aggressively treated, the condition of these patients is likely to progress to renal failure. Anticipating the progression of rhabdomyolysis-induced acute kidney injury is paramount to improving clinical outcomes. Additionally, this case identifies a potential link between the patient’s Huntington’s disease and his abnormally elevated creatine kinase, a finding not described in the literature of rhabdomyolysis-induced kidney injuries to date and an important consideration for future patients with similar comorbidities.

Immune-Mediated Necrotizing Myopathy(IMNM)

Immune-mediated necrotizing myopathy (IMNM) has recently been classified from polymyositis, and it clinically shows subacute progressive proximal dominant muscle weakness. Laboratory examinations show a great increase in serum creatine kinase and prominent necrotic muscle fibers without any pathological invasion of inflammatory cells. It is thought to be an autoimmune disease because SRP and HMGCR antibodies have been detected in many cases. These two antibodies affect the pathophysiology of IMNM. Immuno-modulating therapies have usually been induced. Moreover, intensive treatments are necessary in cases of corticosteroid resistant IMNM.

Comparison of rhabdomyolysis in acutely intoxicated patients with psychotropic and chemical substances.

Rhabdomyolysis is characterized by a muscle injury that leads to the release of intracellular muscle contents/constituents into the systemic circulation.

The Combined Effect of Taurine and Omega-3 Supplementation on Delayed Onset Muscle Soreness in High-Intensity Eccentric Exercise

Background: Eccentric exercise makes more tensions in active muscle fibers, resulting in muscle damage and delayed pain. Therefore, Delayed-Onset Muscle Soreness (DOMS) is a common result of severe eccentric contractions. This study aimed to clarify the combined effect of taurine and omega-3 supplementation on DOMS and muscle damage after high-intensity eccentric exercise in young untrained men.&#x0D; Methods: Forty-eight young untrained males were assigned to four groups (taurine+omega-3 [combined], taurine, omega-3, and one placebo group) and given 1,500 mg taurine and 1,500 mg omega-3 or 1,500 mg taurine or 1,500 mg omega-3 or placebo twice a day respectively. Each group received its supplements for twenty-eight days. DOMS and muscle damage in the lower body developed using a leg press with a weight equivalent to 70% of 1RM (One-Repetition Maximum). Lactate dehydrogenase (LDH), Creatine kinase (CK) and perceived muscle soreness measures were repeated before, immediately, 24, 48, and 72 hr after eccentric activity. p&lt;0.05 was considered to be statistically significant.&#x0D; Results: In the combined group, there was no increase in CK and LDH in immediate time and 72 hr after the exercise, respectively, compared to the period before the workout. At 24 and 48 hr after the training, there was a significant decrease in muscle pain perception in all groups compared to placebo (p&lt;0.05).&#x0D; Coclusion: A combination of 1500 mg taurine and 1500 mg omega-3, two times a day, for four weeks can reduce the levels of CK and LDH enzymes as some indicators of muscle damage. It also attenuates exercise-induced DOMS and muscle damage.

A novel approach to the treatment of high-risk non–muscle-invasive bladder cancer: Combining immune checkpoint inhibitor (ICI) and microtubule inhibitor (MTI).

e16596 Background: Pts with multiple or tumors with large invasion areas that are incompletely resectable through TURBT would be recommended for radical cystectomy in the clinical treatment. The KEYNOTE-057 and SWOG S1605 studies have illuminated the efficacy of immune checkpoint inhibitors monotherapy in HR-NMIBC pts, with acceptable adverse events (AEs). This trial was designed to evaluate the efficacy and safety of tislelizumab (ICI) plus nab-paclitaxel (MTI) in HR-NMIBC pts. Methods: TRUCE-02 is a single-arm phase II study testing systemic tislelizumab 200mg on days 1 plus nab-paclitaxel 200mg on days 2 every 3 weeks (Q3W) for one year for NMIBC pts with incompletely resectable tumor by TURBT. Here we report the results for all eligible patients who received at least one protocol treatment. The primary endpoint was pathological complete response (CR) rate when pts received 3 or 4 cycles of therapy. Duration of complete response (DOR), cystectomy-free survival (CFS), overall survival (OS), and progression-free survival (PFS) using Kaplan-Meier methods (KM) were secondary endpoints. Results: Between July 2020 and December 2022, 69 pts were enrolled and included in the safety analysis, and, of those, 56 pts were eligible and included in the efficacy analysis. 34 (60.7%; 95% CI 46.8%, 73.2%) out of 56 pts achieved CR condition when completing 3 or 4 treatment cycles. At 12 months, the estimated DOR after CR was 88.1% (95% CI 76.2%, 99.9%); the median DOR was not reached. At 18 months, the estimated CFS was 70.0% (95% CI 58.1%, 84.3%), OS was 90.6% (95% CI 82.9%, 99.0%), and PFS was 74.4% (95% CI 62.5%,80.0%); the median CFS, OS, and PRS were not reached. 65 (94%) of 69 pts had treatment-related adverse events (trAEs). The most common trAEs were alopecia 47(68%), fatigue 44(64%), and rash 25(36%). 8 grade 3-4 trAEs occurred in 6 (9%) pts, including adrenal insufficiency in 2 (3%), rash in 1 (1%), myalgia or arthralgia in 1 (1%), increased creatine kinase isoenzyme in 1 (1%), hepatic enzymes increase in 1 (1%), increased glutamyl transpeptidase in 1 (1%), and decreased white blood cell count in 1 (1%). No trAE-related death was reported. Conclusions: Tislelizumab with nab-paclitaxel represents a novel treatment option with a durable and clinically meaningful activity in treating HR-NMIBC. The safety profile was consistent with that of previous experience and no new safety concerns. Clinical trial information: NCT04730232 .

Medical causes of poor performance and their associations with fitness in Standardbred racehorses.

Poor performance is a multifactorial syndrome of racehorses, commonly associated with subclinical disorders, which can be diagnosed by exercise testing. Describe the prevalence of medical causes of poor performance in Standardbreds unassociated with lameness, and evaluate their relationships with fitness variables measured by exercise treadmill test. Hospital population of 259 nonlame Standardbred trotters referred for poor performance. The horses' medical records were retrospectively reviewed. Horses underwent a diagnostic protocol including resting examination, plasma lactate concentration, treadmill test with continuous ECG and assessment of fitness variables, creatine kinase activity, treadmill endoscopy, postexercise tracheobronchoscopy, bronchoalveolar lavage (BAL), and gastroscopy. The prevalence of different disorders was evaluated, including cardiac arrhythmias, exertional myopathies, dynamic upper airway obstructions (DUAOs), exercise-induced pulmonary hemorrhage (EIPH), moderate equine asthma (MEA), and gastric ulcers (EGUS). The associations of these disorders with fitness variables were investigated individually and using multivariable models. Moderate equine asthma and EGUS were the most common disorders, followed by EIPH, DUAOs, cardiac arrhythmias, and exertional myopathies. Hemosiderin score was positively correlated with BAL neutrophils, eosinophils, and mast cells; increased creatine kinase activity was associated with BAL neutrophilia, DUAOs, premature complexes, and squamous gastric disease. Treadmill velocity at a plasma lactate concentration of 4 mmol/L and at heart rate of 200 beats per minute was negatively affected by BAL neutrophilia, multiple DUAOs, exertional myopathies, and squamous gastric disease. The multifactorial nature of poor performance was confirmed, with MEA, DUAOs, myopathies and EGUS representing the main diseases involved in fitness impairment.

Випадок мітохондріальної епізодичної міопатії (варіант без атрофії зорового нерва та оборотної лейкоенцефалопатії) у Прикарпатті

Mitochondrial episodic myopathy with/or without optic nerve atrophy and reversible leukoencephalopathy (MEOAL, OMIM 251900) belongs to rare primary mitochondrial myopathies, caused by nuclear genome DNA mutations with autosomal recessive inheritance. Purpose - to inform about the case of this current rare mitochondrial miopathy and encrease the knowledge of practical doctors in scope of diagnostics and treatment of the current orphan pathology Clinical case. In the clinical case being presented herein, the sick child had a severe course of the disease in the form of episodes of severe myopathy (during one of them there was a need for long-term mechanical lungventilation with the placement of a tracheostomy) in combination with severe metabolic crises. During crises, persistent keto- and lactic acidosis, a sharp increase in transaminases (alanine aminotransferase and aspartate aminotransferase) and creatine kinase in blood serum were observed. The patient did not have optic nerve atrophy or leukoencephalopathy. A similar course of the disease is described in the literature by different authors in only 3 cases. Molecular genetic analysis (Invitae laboratory, San Francisco) revealed 2 mutations of the FDX2 gene (the disease is associated with this gene) with uncertain pathogenic significance. Considering the presence of cardinal symptoms of MEOAL, this diagnosis was set to the patient, and therefore the detected mutations of the FDX2 gene should be considered as pathogenic. Conclusions. A thorough syndromic analysis of the phenotype together with a set of paraclinical examinations, including modern molecular genetic methods, made it possible to establish a clinical diagnosis of an extremely rare primary mitochondrial myopathy, which will contribute to further elucidation of relationships in the «genotype-phenotype» system and, possibly, reclassification of pathogenic genotypes in modern databases, as well as finding optimal approaches in treatment and rehabilitation of patients. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Brigatinib-associated autoimmune hepatitis: A case report

Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor that targets a wide variety of ALK mutations and ROS1 rearrangements. While pancreatic enzyme elevations due to brigatinib are well known, we wanted to present a case that caused liver toxicity. ALK and ROS1 translocations were detected in a 58-year-old patient diagnosed with metastatic lung adenocarcinoma. In the patient who had a good response with brigatinib, more than 5-fold elevation was detected in liver enzymes at the fifth month of treatment. After excluding other hepatitis factors, the patient was thought to have autoimmune hepatitis, and methylprednisolone was started and liver enzymes were decreased. Increased creatine kinase and lipase levels are common side effects associated with brigatinib, while liver toxicity is rare. Autoimmune hepatitis due to brigatinib was considered because of hepatic toxicity that developed in the fifth month of treatment and responded well to steroids.

Polysaccharide storage myopathy in two Percheron horses

Polysaccharide storage myopathy (PSSM) is a genetic disorder or by undetermined cause characterized by the abnormal accumulation of glycogen and polysaccharides in skeletal muscle fibers. The present report describes two Percheron horses, from different properties in the municipality of Pouso Redondo - SC, with locomotor clinical signs that started after work. The clinical signs observed were rigid gait, mainly of the pelvic limbs, muscle weakness, and recumbency. In the first case, the animal was diagnosed with severe multifocal rhabdomyonecrosis, moderate multifocal myoglobin nephrosis and severe diffuse transmural fibrinonecrotic gastritis. PSSM was confirmed by the presence of polysaccharide inclusions in myofiber sarcolemma visualized by periodic acid-Schiff (PAS) staining. In the second case, the horse presented two episodes of muscle disorder after work. The therapeutic protocol was based on penicillin, flunixin meglumine and fluid therapy with ringer lactate. An increase in creatine kinase (669.0 UI/L) and aspartate aminotransferase (669.0 UI/L) was observed in the serum biochemical evaluation. Research for mutation in the GYS1 gene was performed, with a positive heterozygote result. After rest and gradual recovery, the horse was only submitted to light work, with no return of the clinical condition since then. Thus, this report describes two cases of PSSM with distinct clinical evolution and diagnostic methods.

The cholesterol-lowering effect of statins is modified by LILRB5 intolerance genotype: Results from a recruit-by-genotype clinical trial.

Background/Aims: Statin intolerance leads to poor adherence to statin therapy, resulting in a failure to achieve desired cholesterol reduction and adverse outcomes. The LILRB5 Asp247Gly genotype has been identified as being associated with statin intolerance and statin-induced myalgia. We conducted a randomized clinical trial to examine its role in immune response through T regulatory cell aggregation and in achieving cholesterol reduction targets. Methods: A double-blind, cross-over, recruit-by-genotype trial was undertaken. A total of 18 participants who had either the Asp247Asp (T/T) genotype or the Gly247Gly (C/C) genotype were recruited to the study. Participants were randomised to receive placebo or atorvastatin 80mg daily for 28days. Following a washout period of 3weeks, they were then switched to the opposite treatment. Biochemical and immunological measurements as well as interviews were performed prior to and after both treatment periods. Within genotype group comparisons were performed using repeated measures Wilcoxon tests. Two-way repeated measures ANOVA with genotype and treatment as factors were used to compare changes in biochemical parameters between groups during placebo and atorvastatin periods. Results: Individuals with the Asp247Asp genotype had a greater increase in creatine kinase (CK) compared to those with Gly247Gly genotype in response to atorvastatin (p = 0.03). Those with Gly247Gly genotype had a mean non-HDL cholesterol reduction of 2.44 (95% CI:1.59 - 3.29) mmol/L while in Asp247Asp genotype group the mean reduction was 1.28 (95%CI: 0.48 - 2.07) mmol/L. The interaction between the genotype and atorvastatin treatment for total cholesterol (p = 0.007) and non-HDL cholesterol response was significant (p = 0.025). Immunological assessment showed no significant changes in aggregation of T regulatory cells by genotype. Conclusion: The Asp247Gly variant in LILRB5, previously associated with statin intolerance, was associated with differential increases in creatine kinase and total cholesterol and non-HDL cholesterol-lowering response to atorvastatin. Taken together, these results suggest that this variant could have utility in precision cardiovascular therapy.

Upadacitinib for the treatment of psoriatic arthritis.

Psoriatic arthritis is a chronic systemic inflammatory disease that presents with a variable clinical course and is typically associated with joint inflammation, together with cutaneous psoriasis. In recent decades, knowledge of the pathogenesis of psoriatic arthritis has advanced considerably and has allowed for development of new highly effective therapies, transforming the treatment landscape. Upadacitinib is a Janus kinase inhibitor (JAK) that is orally reversible with high selectivity for JAK1 and its signal transduction molecules. The results obtained in the phase III clinical trials (SELECT-PsA 1 and SELEC-PsA 2) demonstrated that upadacitinib was highly effective over placebo and non-inferior to adalimumab in several important domains of the disease. Improvements were observed in dactylitis, enthesitis and spondylitis as well as in physical function, pain, fatigue and overall quality of life. The safety profile of these results resembled that of adalimumab, apart from a slightly higher rate of herpes zoster infection, an increase of creatine kinase and an incidence of lymphopenia. However, none of these events was considered a serious adverse advent. Additionally, another analysis demonstrated that combining upadacitinib with methotrexate was associated with a similar efficacy to upadacitinib in monotherapy, both for patients that are naive to biologics treatment and for those previously treated with biologics. Therefore, upadacitinib is a new option for the treatment of psoriatic arthritis, presenting a series of beneficial characteristics. At this stage, it is important to collect long-term data to confirm the efficacy and safety profiles shown in clinical trials.

Metabolic adverse effects of antipsychotics: the state of the problem and management options

Antipsychotic drugs are widely used for many psychiatric disorders, such as schizophrenia, bipolar affective disorder, delusions and hallucinations due to neurological disorders, depression with severe psychotic symptoms. Metabolic disorders including weight gain, dyslipidemia and hyperglycemia are one of the most common side effects of antipsychotic therapy. Psychiatric patients have higher risk of cardiovascular disease, so that the development of metabolic side effects is an important clinical problem that should be solved. Antipsychotic-induced weight gain may cause distress that leads to antipsychotics withdraw and repeated hospitalizations. Lifestyle changes, correction of the antipsychotic treatment, additional medications and their combination are the possible solutions of antipsychotic metabolic side effects. Lifestyle modification is a first-line therapy that should complement other options, when it feasible. At the same time, it can be extremely difficult for patients receiving antipsychotic to adhere dietary and physical activity recommendations. Replacing an antipsychotic with a milder drug is not always possible and may not be enough effective. Metformin seems to be the most well-studied, safe and effective agent that is prescribed to deal with antipsychotic-induced weight gain and associated metabolic disorders. Glucagon-like peptide type 1 receptor agonists and thiazolidinediones are mentioned as alternative medications, but clinical data on their efficacy and safety in this patient group are extremely limited. Dyslipidemia can develop as an independent antipsychotic side effect even without an increase in body weight. The most effective treatment, as in the general population, is statin therapy. However, the joint appointment of statins and antipsychotic significantly increases the risk of adverse reactions, such as myalgia, myopathy, increased creatine kinase levels, due to the competition of drugs for the cytochrome system. It is still unknown what scales should be used for cardiovascular risk stratification in patients taking antipsychotic and whether it is possible to use metformin to prevent antipsychotic-induced weight gain, and if so, how to select patients for whom such therapy can be indicated. Finally, more clinical trials are needed to evaluate the efficacy and safety of other classes of hypoglycemic and lipid-lowering drugs in patients on antipsychotics.

Creatine kinase is associated with glycated haemoglobin in a nondiabetic population. The Tromsø study.

Creatine kinase (CK) has been associated with insulin resistance and identified as a risk marker of cardiovascular disease largely by its relationship with hypertension and increased body mass index. This study determined whether CK is a predictor of glycated haemoglobin (HbA1C) in a nondiabetic general population. Associations between CK and the outcome variable HbA1C (%) were performed by variance and multivariate analyses in 11662 nondiabetic subjects defined as HbA1C (%) <6.5 who participated in the population based Tromsø study (Tromsø 6) in Norway. Abnormal elevated CK was detected in 543/11662 participants (4.66%). Mean HbA1C (%) in the "high CK" group was 5.62 (SD = 0.33) compared to 5.52 (SD = 0.36) in the "normal CK" group, P <0.001. CK increased significantly and linearly with higher levels of HbA1C (%) quartiles in women (P <0.001) and non-linearly in men (P <0.001). In a multivariate analysis, CK was independently associated with HbA1C (%) after adjusting for age, sex, body mass index, blood pressure, glucose, lipids, C-reactive protein, creatinine, alanine transaminase and aspartate aminotransferase. A 1-unit increase in log CK was associated with a 0.17-unit increase in HbA1C (%). These data demonstrate a positive and independent association between CK and glycated haemoglobin in a nondiabetic general population.

Toxic effect of cigarette butts leachates on blood markers of Periophthalmus waltoni species from the Persian Gulf region

Cigarette butts (CBs) are one of the most common, long-lasting, and toxic forms of marine and coastal area debris. Although the significance of CBs and the toxic contents of this waste items are well recognized, but there is still a lack of information about the effects of this waste on the aquatic organisms. Therefore in this study, the in-vivo toxic effects of various CBs leachates (smoked cigarette butts with tobacco [SCBs], smoked CBs without tobacco [SFs], and unsmoked filters [USFs]) on cellular and chemical hematologic markers in fish (Periophthalmus waltoni) were evaluated. In three acute, sub-acute, and sub-chronic exposure measurements, P. waltoni exposed to different CBs leachates showed a significant increase in white blood cells, creatine kinase, lactate dehydrogenase, alkaline phosphatase, alanine transaminase, and aspartate transaminase, as well as a decrease in hemoglobin (Hb) levels. The mean ± SD values of Hb in P. waltoni species exposed to different CBs leachates (control, SCBs, SFs and USFs) in acute (1 day) phase were 7.15 ± 0.34, 6.02 ± 0.29, 6.25 ± 0.25 and 6.89 ± 0.1 g/dl respectively. These values in subacute (28 days) phase were 6.70 ± 0.15, 5.19 ± 0.24, 5.67 ± 0.30 and 6.10 ± 0.24 g/dl and in sub chronic exposure (42 days) phase were 7.20 ± 0.40, 5.16 ± 0.30, 5.88 ± 0.34 and 6.60 ± 0.33 g/dl respectively. Our results showed that CBs leachates act as a stressor, leading to changes in some hematologic markers in P. waltoni species. Because of the continued deposition of CBs waste into global aquatic environments, policies to mitigate this waste in coastal areas are needed to prevent potentially negative effects on fish and other aquatic organisms.