Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation.

Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.

Naja nigricincta nigricincta venom, a murine model. Evaluation of skeletal and cardio-myonecrosis, kidney injury and inflammatory response along with neutralisation efficacy by the SAIMR/SAVP - And EchiTAb-Plus-ICP polyvalent antivenoms.

African spitting cobra, Naja nigricincta nigricincta (Zebra snake), envenomation is an important cause of snakebite morbidity and mortality in Namibia. The snake is endemic to central and northern Namibia as well as southern Angola. The venom is mainly cytotoxic, resulting in aggressive dermo-necrosis and often accompanied by severe systemic complications. No specific antivenom exists. Rhabdomyolysis, systemic inflammatory response, haemostatic abnormalities, infective necrotising fasciitis as well as acute kidney failure have been documented. Based on murine models, this study assessed SAVP/SAIMR - and EchiTAb-Plus-ICP polyvalent antivenom neutralisation as well as subdermal necrosis. Additional muscle, cardiac, kidney and lung histology, creatine kinase measurements and post-mortems were performed. An intravenous median lethal dose (LD50) of Naja nigricincta nigricincta venom was determined at 18.4 (CI: 16.3; 20.52) µg and a subdermal lethal dose at 15.3(CI: 12.96; 17.74)µg. The SAIMR/SAVP polyvalent antivenom median effective dose (ED50) was 1.2 ml antivenom/1 mg venom equating to a potency (WHO) of 1 ml antivenom neutralising 0.63 mg venom and approximately 240 ml (24 vials) needed for initial treatment. The ED50 of the EchiTAb-Plus-ICP was 1 ml antivenom/1 mg venom and a potency of 65 mg venom/ml antivenom (3.3 x LD50), estimating 230 ml (23 vials) for treatment. Histology and serology (creatine kinase) evidenced venom induced skeletal myotoxicity, which was not prevented by the antivenoms tested. Cardiac myonecrosis, an inflammatory response, direct venom kidney tubular necrosis and cardio-pulmonary failure were documented.

Prognostic value of creatine kinase (CK)-MB to total-CK ratio in colorectal cancer patients after curative resection.

OBJECTIVES: This study aimed to evaluate the prognostic significance of postoperative Creatine Kinase type M and B (CK-MB) to total Creatine Kinase (CK) ratio (CK-MB/CK) in colorectal cancer (CRC) patients after radical resection. METHODS: This was a single-center retrospective cohort analysis. Subjects were stage I-III CRC patients hospitalized in Sichuan Cancer Hospital from January 2017 to May 2021. Patients were divided into abnormal group and normal group according to whether the CK-MB/CK ratio was abnormal after surgery. Through a comparative analysis of clinical data, laboratory test results, and prognosis differences between the two groups, we aimed to uncover the potential relationship between abnormal CK-MB > CK results and CRC patients. To gauge the impact of CK-MB/CK on overall survival (OS) and disease-free survival (DFS), we employed the multivariable COX regression and LASSO regression analysis. Additionally, Spearman correlation analysis, logistic regression, and receiver-operating characteristic (ROC) curve analysis were conducted to assess the predictive value of the CK-MB/CK ratio for postoperative liver metastasis. RESULTS: Cox regression analysis revealed that the CK-MB/CK ratio was a stable risk factors for OS (HR = 3.82, p < 0.001) and DFS (HR = 2.31, p < 0.001). To distinguish hepatic metastases after surgery, the ROC area under the curve of CK-MB/CK was 0.697 (p < 0.001), and the optimal cut-off value determined by the Youden index was 0.347. CONCLUSIONS: Postoperative abnormal CK-MB/CK ratio predicts worse prognosis in CRC patients after radical resection and serves as a useful biomarker for detecting postoperative liver metastasis.

Incidence, characteristics, and risk factors of drug-associated muscle adverse reaction: a retrospective real-world study of inpatients.

OBJECTIVE: To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use. METHODS: We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses. RESULTS: Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs. CONCLUSION: Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life.

Immune-mediated necrotizing myopathy (NAM) related to SARS-Cov-2 infection: a case report.

BACKGROUND: There is a growing body of evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of autoimmune diseases. A recent systematic review reported that the new-onset autoimmune disorders during or after COVID-19 infection included inflammatory myopathies such as immune-mediated necrotizing myopathies. CASE PRESENTATION: We described a 60-year-old man diagnosed with COVID-19 infection and later presented with a two-week history of myalgia, progressive limb weakness, and dysphagia. He had a Creatinine Kinase (CK) level of more than 10,000 U/L, was strongly positive for anti-signal recognition particle (SRP) and anti-Ro52 antibody, and a muscle biopsy revealed a paucity-inflammation necrotizing myopathy with randomly distributed necrotic fibers, which was consistent with necrotizing autoimmune myositis (NAM). He responded well clinically and biochemically to intravenous immunoglobulin, steroids and immunosuppressant and he was able to resume to his baseline. CONCLUSION: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.

Effects of photobiomodulation and deep water running in patients with chronic non-specific low back pain: a randomized controlled trial.

Photobiomodulation therapy (PBM) is often used to treat musculoskeletal disorders such as chronic non-specific low back pain (NSCLBP) as it can have positive effects on biomarkers-creatine kinase (CK) and serum cortisol levels-related to stress caused by physical exercise, such as deep water running (DWR) or by pain. The aim of this study was to evaluate the effects of the combination of PBM and aquatic exercise (DWR) on the intensity of pain, disability, 6-min walk test adapted (6WTA), and on cortisol and creatine kinase (CK) levels in a population with NSCLBP. The participants were allocated into three groups: TGPBM (Photobiomodulation and Training Group), TGPLA (Placebo Photobiomodulation and Training Group), and the GPBM (Photobiomodulation Group). Information regarding anthropometric data, blood pressure, and heart rate were collected, and the questionnaires were applied: IPAQ-Short Form, Oswestry Disability Index, and the Visual Analog Scale for Pain. The submaximal exercise test (6WTA) was performed. Blood was collected for analysis of cortisol and CK levels. The training sessions were performed twice a week, for 4 weeks. In the intragroup comparisons, there were statistically significant changes in the TGPBM and GPBM groups in the outcomes pain intensity, disability (reductions in both groups), and in cortisol (increased in the TGPBM and reduced in the GPBM); in the TGPLA group, there was a statistically significant reduction only in the outcome of pain intensity. In the intergroup comparison, in the comparison between TGPBM and TGPLA, there was a statistically significant difference in the level of cortisol, as well as in the comparison between TGPBM and GPBM, in which there was a statistically significant difference for this same outcome (cortisol) and for the 6WTA outcome. The effects of the combination of PBM and aquatic exercise have positive effects on reducing pain intensity, disability, and cortisol levels, but its effects on other variables (6WTA and CK) are too small to be considered significant. Trial registration number: NCT03465228-April 3, 2019; retrospectively registered (ClinicalTrials.gov).

ROS and iron homeostasis dependent ferroptosis play a vital role in 5-Fluorouracil induced cardiotoxicity in vitro and in vivo.

5-Fluorouracil (5-FU) was a key chemotherapeutic agent in the treatment of different solid tumors. However, cardiotoxicity was included among the therapeutic strategies of 5-FU. The molecular mechanism of cardiotoxicity induced by 5-FU remains unclear. The aim of the study was to investigate whether ferroptosis was involved in 5-FU-induced cardiotoxicity in vivo and in vitro. The in vivo cardiotoxicity model was induced by intraperitoneal injection of 5-FU at the dose of 15, 30, 60 mg/kg for 7 days. Body weight, general condition and plasma enzyme activities of the mice were observed to evaluate heart function. In addition, HE staining, MASSON staining and TEM technology was used. Western-blot analysis were performed to evaluate the protein level of iron transport, iron storage and reactive oxygen species (ROS) of ferroptosis. In H9c2 cardiomyocyte cells, cell viability, generation of ROS, mitochondrial activity and cellular Fe2+ levels were measured. The in vivo results showed that 5-FU significantly impaired cardiac function and structure. The serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels were significantly increased in 5-FU group. HE and MASSON staining showed that 5-FU caused structural injuries. In addition, 5-FU increased the level of ferroptosis markers involving malonaldehyde (MDA) and Fe2+ content. Ferrostatin-1 (Fer-1) was an aromatic amine that specifically binds with lipid ROS and protects cells against lipid peroxidation. Furthermore, 5-FU markedly induced ferroptosis in H9c2 cardiomyocyte cells, which mainly embodied as declined cell vitality, accumulated iron, elevated lipid peroxides. Conversely, inhibition of ferroptosis by Fer-1 completely abolished 5-FU-induced effects. Both in vivo and in vitro experiments indicated that 5-FU increased the expression of ferroptosis, mainly by reducing the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1), but enhancing the expression of transferrin receptor 1 (TfR1). In conclusion, the present study suggested that ROS and iron homeostasis dependent ferroptosis played a vital role in 5-FU induced cardiotoxicity.

Genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity after prolonged running in men.

This study aimed to clarify 1) the influence of genetic polymorphisms in the cytochrome P450 aromatase gene (CYP19A1) on circulating estradiol levels in men and 2) whether estrogen-related genetic polymorphisms, such as the CYP19A1 rs936306 and estrogen receptor-α (ESR1) rs2234693 polymorphisms, predict exercise-induced serum creatine kinase (CK) activity, which is an index of skeletal muscle membrane disruption. Serum estradiol levels were examined in young men (n = 167). In a different cohort, serum CK activity was analyzed in a 2-day ultramarathon race: baseline, after the first day, and after the second day (114 males and 25 females). Genetic polymorphisms in CYP19A1 rs936306 C/T and ESR1 rs2234693 T/C were analyzed using the TaqMan SNP Genotyping Assay. Male subjects with the TT genotype of the CYP19A1 polymorphism exhibited significantly higher serum estradiol levels than the C allele carriers. Male runners had significantly higher postrace serum CK activity than female runners. The change in the CK activity during the ultramarathon race was significantly lower in male subjects with the CYP19A1 TT genotype than in those with the CC + CT genotypes and was correlated with the number of C alleles in ESR1 rs2234693 in male subjects. Furthermore, the genotype scores of these two polymorphisms were significantly correlated with changes in serum CK activity during race (r = -0.279, P = 0.003). The results of this study suggest that genetic polymorphisms in CYP19A1 rs936306 influence serum estradiol levels in men, and genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity in men.NEW & NOTEWORTHY Men with the TT genotype of the CYP19A1 polymorphism exhibited higher circulating estradiol levels than the TC + CC genotype. The TT genotype in the CYP19A1 polymorphism and the C allele of the ESR1 polymorphism, an allele increasing ESR1 expression, were associated with low serum CK activity after the ultramarathon. A combination of these polymorphisms was correlated with changes in the serum CK activity. Therefore, estrogen-related genetic polymorphisms partially predict exercise-induced muscle damage, that is, skeletal muscle membrane disruption.

Ursolic acid increases strength in mdx mice model and may decrease fibrosis deposition by tgf-ß downregulation / El ácido ursólico aumenta la resistencia en el modelo de ratones mdx y podría disminuir la deposición de fibrosis mediante la regulación decreciente de tgf-ß

SUMMARY: Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

RESUMEN: La disfunción de la distrofina resulta en la desestabilización del sarcolema, llevando al daño de las células musculares por ciclos continuos de degeneración y regeneración limitada. En la distrofia muscular, debido a la disfunción de la distrofina, la inflamación, la necrosis y la fibrosis, son características fisiopatológicas de la pérdida de la función muscular. Como enfermedad genetica no es possible remediar esta distrofia muscular, sin embargo, los avances en la terapia de medicamentos con glucocorticoides pueden disminuir la progresión de la enfermedad. Se estudiaron terapias alternativas, como el ácido ursólico (UA), que inhibe la atrofia muscular y aumenta la masa y la fuerza muscular. En este estudio, utilizamos una suplementación diaria de 10 mg / kg en ratones mdx durante 4 semanas para evaluar la creatina fosfoquinasa (CPK) sérica, la fuerza muscular (prueba de Kondziela), la organización muscular (histología) y la expresión de genes relacionados con la fibrosis (TGF-ß, TNF- α, mstn y ostn). La suplementación con AU aumentó la organización morfológica muscular, la fuerza motora y la disminución de la expresión muscular de TGF-ß. El perfil de expresión génica, la organización histológica y la fuerza simultáneamente podrían sugerir que el tratamiento con AU no detuvo la fibrogénesis sino que disminuyó su progreso.

[Anti-mitochondrial M2 antibody-positive myositis preceded by heart failure and cardiac conduction disturbance. A case report].

A 69-year-old man visited our hospital complaining of fatigue in the lower extremities while walking. The patient had a two-year history of congestive heart failure and received a permanent artificial pacemaker implantation for sick sinus syndrome. Physical examination revealed proximal muscle weakness and exaggerated lumbar lordosis. Serum creatine kinase level was 1,455 U/l. The atrophies of the paraspinal muscles at thoracic to lumbar spine levels, rectus abdominis and soleus muscles were detected on computed tomography. Muscle biopsy showed mild to moderate variability in muscle fiber size with regenerating and necrotic muscle fibers. Mononuclear cell infiltration was not found. HLA-ABC expression was minimum. After anti-mitochondrial M2 antibody was detected, administration of oral prednisolone resulted in improvements in muscle strength and serum creatine kinase level. Based on the clinical course, examination and clinical findings, the patient was diagnosed as anti-mitochondrial M2 antibody positive myositis. Anti-mitochondrial M2 positive myositis is not only difficult to diagnose by muscle biopsy, but can also be preceded or complicated by fatal cardiac complications.

Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial.

BACKGROUND: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma. METHODS: For this single-arm, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma (stage Ib, II, and IIIb) were enrolled and received two cycles of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by surgical resection. Eligible patients were aged 18 years or older, had confirmed resectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate liver function. Patients were excluded if they had metastatic disease, if the surgery was not expected to be curative, if they had a known additional malignancy requiring active treatment, or if they required systemic steroid treatment or any other immunosuppressive therapy. After resection, patients received an additional eight cycles of cemiplimab 350 mg intravenously every 3 weeks in the adjuvant setting. The primary endpoint was significant tumour necrosis on pathological examination (defined as >70% necrosis of the resected tumour). Secondary endpoints included delay of surgery, the proportion of patients with an overall response, change in CD8+ T-cell density, and adverse events. Tumour necrosis and response were analysed in all patients who received at least one dose of cemiplimab and completed surgical resection; safety and other endpoints were analysed in the intention-to-treat population. Patients underwent pre-treatment biopsies and blood collection throughout treatment. This trial is registered with ClinicalTrials.gov (NCT03916627, Cohort B) and is ongoing. FINDINGS: Between Aug 5, 2019, and Nov 25, 2020, 21 patients were enrolled. All patients received neoadjuvant cemiplimab, and 20 patients underwent successful resection. Of the 20 patients with resected tumours, four (20%) had significant tumour necrosis. Three (15%) of 20 patients had a partial response, and all other patients maintained stable disease. 20 (95%) patients had a treatment-emergent adverse event of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were increased aspartate aminotransferase (in four patients), increased blood creatine phosphokinase (in three), constipation (in three), and fatigue (in three). Seven patients had grade 3 adverse events, including increased blood creatine phosphokinase (in two patients) and hypoalbuminaemia (in one). No grade 4 or 5 events were observed. One patient developed pneumonitis, which led to a delay in surgery by 2 weeks. INTERPRETATION: This report is, to our knowledge, the largest clinical trial of a neoadjuvant anti-PD-1 monotherapy reported to date in hepatocellular carcinoma. The observed pathological responses to cemiplimab in this cohort support the design of larger trials to identify the optimal treatment duration and definitively establish the clinical benefit of preoperative PD-1 blockade in patients with hepatocellular carcinoma. FUNDING: Regeneron Pharmaceuticals.

Neuroleptic Malignant Syndrome: A Potential Etiology of Multisystem Organ Failure in a Burn Patient.

Neuroleptic malignant syndrome (NMS) is described in the medical literature but rarely seen among acutely ill trauma patients. A 44-year-old man with burns to the hands and back after a chemical explosion was transported to an outside facility where he received treatment for presumed acute coronary syndrome after developing ventricular tachycardia and elevated serum troponins after the exposure. His cardiac catheterization was unremarkable, but an echocardiogram revealed severe cardiomyopathy, and he was also in multisystem organ failure. He was transferred to our facility after hospital day 2 for treatment of his multisystem organ failure and 2% total body surface area burns. His laboratory results were remarkable for a creatine kinase of >100 000 units/L, and he required 14 g of intravenous calcium. Upon further investigation, the patient reported taking ziprasidone for his bipolar disorder, and he had a core temperature of 103.5 °F on his initial presentation to the outside facility. As he convalesced, the unifying diagnosis was NMS. NMS is a side effect of antipsychotic therapy and is manifested by hyperpyrexia, rigidity, autonomic instability, and altered consciousness. An elevated creatine kinase >100 000 units/L is almost pathognomonic for NMS. Patients can also present with leukocytosis, organ failure, and electrolyte disturbances including hypocalcemia. We hypothesized that dehydration, the warm environmental conditions at our patient's job, and immense stress resulting in a catecholamine surge following his trauma were inciting triggers to this event. This case highlights the importance of considering alternate diagnoses in patients whose clinical presentation does not fit the most "obvious cause."

Increasing the resting time between drop jumps lessens delayed-onset muscle soreness and limits the extent of prolonged low-frequency force depression in human knee extensor muscles.

PURPOSE: Unaccustomed eccentric contractions generally result in a long-lasting contractile impairment, referred to as prolonged low-frequency force depression (PLFFD), and delayed-onset muscle soreness (DOMS). We here used repeated drop jumps (DJs) as an eccentric contraction model and studied the effects of increasing the time between DJs from 20 s to 5 min. We hypothesized that both PLFFD and DOMS would be less marked at the longer DJ interval due to the longer time to restore structural elements between DJs. METHODS: Young men (n = 12) randomly performed 50 DJs with either 20-s (DJ-20 s) or 5-min (DJ-5 min) rest between DJs. Voluntary, 20 Hz and 100 Hz electrically stimulated isometric knee extension torques and muscle soreness were monitored before and for 7 days after DJs; serum CK activity was measured to assess muscle fibre protein leakage. In additional experiments, changes in mRNA levels were assessed in muscle biopsies collected before and 1 h after exercise. RESULTS: A marked PLFFD was observed with both protocols and the extent of 20 Hz torque depression was smaller immediately and 1 day after DJ-5 min than after DJ-20 s (p < 0.05), whereas the MVC and 100 Hz torques were similarly decreased with the two protocols. Markedly larger differences between the two protocols were observed for the muscle soreness score, which 1-4 days after exercise was about two times larger with DJ-20 s than with DJ-5 min (p < 0.01). CONCLUSIONS: The larger protective effect of the longer DJ interval against DOMS than against PLFFD indicates that their underlying mechanisms involve different structural elements.

The role of serum creatine kinase levels in anterior cervical spinal surgery: Change trends and risk factors.

ABSTRACT: This study aimed to describe change trends in serum creatine kinase (CK) values for patients undergoing anterior cervical spinal surgery and identify risk factors that affect the CK values perioperatively, intending to decrease the degree of the iatrogenic invasiveness of the procedure.We retrospectively analyzed 122 patients undergoing anterior cervical spinal surgery from January 2019 to May 2020. For all patients, CK level was measured 1 day before the operation. Daily CK levels were evaluated on postoperative days 1 to 7. These data were analyzed in terms of age, gender, the use of microendoscopy during surgery, the number of cervical operative segments, and operative methods to determine whether these risk factors influenced postoperative CK increases.A total of 122 patients were enrolled. The preoperative average CK level was 72.7 U/L, and the average CK levels were 130.6, 122.4, 99.1, 82.8, 73.7, 63.9, and 55.4 U/L from the postoperative day (POD) 1 to POD7, respectively. CK level changes on POD1 increased with the number of operated cervical segments. However, changes were not related to age, gender, microendoscopy, or the operative method.Increased serum CK level was associated with the number of cervical operative segments, rather than age, gender, the use of microendoscopy, or the operative methods. These findings suggest that the number of cervical operative segments determined the degree of iatrogenic injury for anterior cervical spinal surgery.

Anesthetic management with remimazolam for a pediatric patient with Duchenne muscular dystrophy.

RATIONALE: With Duchenne muscular dystrophy (DMD) being the most common and most severe type of muscular dystrophy, DMD patients are at risk for complications from general anesthesia due to impaired cardiac and respiratory functions as the pathological condition progresses. In recent years, advances in multidisciplinary treatment have improved the prognosis of DMD patients, and the number of patients requiring surgery has increased. Remimazolam is a benzodiazepine derivative similar to midazolam. Its circulatory stability and the fact that it has an antagonist make it superior to propofol.There are no reports of pediatric patients with DMD undergoing total intravenous anesthesia with remimazolam. PATIENT CONCERNS: A 4-year boy was scheduled for single-incision laparoscopic percutaneous extraperitoneal closure for inguinal hernia under general anesthesia, but the surgery was postponed because his serum creatine phosphokinase level was extremely high. DIAGNOSIS: He was diagnosed with DMD. According to the results of the genetic test, exon deletion of the DMD gene was detected using multiplex ligation-dependent probe amplification, although he had no symptoms of DMD except for elevated serum levels of creatine phosphokinase, etc. INTERVENTION: He was admitted for the same surgical purpose. Anesthesia was induced with 3 mg of intravenously administered remimazolam. He lost the ability to respond to verbal commands. After the intravenous administration of 100 µg of fentanyl, a continuous infusion of remifentanil (1.0 µg/kg/min) and remimazolam (15 mg/h) was started, and the endotracheal tube was inserted smoothly after the administration of 10 mg of rocuronium with which the muscle twitches disappeared in train-of-four monitoring. At the end of the surgery, 15 mg of flurbiprofen was administered intravenously. After surgery, we injected 40 mg of sugammadex to confirm a train-of-four count of 100%. OUTCOMES: Although the dose of remimazolam was reduced to 5 mg/h 30 minutes before the end of the surgery, it took 20 minutes after the discontinuation of remimazolam for the patient to open his eyes upon verbal command. On postoperative Day 2, he was discharged from the hospital without any complications. LESSONS: Remimazolam was shown to be safe to use for general anesthesia in a pediatric patient with DMD.

Absence of significant clinical benefit for a systematic routine creatine phosphokinase measurement in asymptomatic patients treated with anti-programmed death protein (ligand) 1 immune checkpoint inhibitor to screen cardiac or neuromuscular immune-related toxicities.

AIM: Despite unprecedented results of anti-programmed death protein (ligand) 1 (PD-(L)1) immune checkpoint inhibitor in the oncology's armamentarium, immune-related adverse events (irAEs) represent a therapeutic hurdle. Currently, there is no consensual recommendation on a routinely monitored biomarker to early detect irAE. Biological markers such as serum creatine phosphokinase (CPK) are commonly used to measure muscular tissue injury. The potential of routine serum CPK monitoring to predict cardiac or neuromuscular irAE in patients treated with immunotherapy remains unknown. METHODS: In this retrospective study between January 2016 and December 2018 at Gustave Roussy Cancer Campus, 1151 cancer patients treated with anti-PD-(L)1 immunotherapy were systematically monitored with serum CPK measurements before each immunotherapy cycle. We considered significant CPK increases according to Common Terminology Criteria for Adverse Events v5.0 (CTCAEV5) of grade ≥2 severity. Comparisons were performed in patients with immune-related CPK (ir-CPK) elevations symptomatic versus asymptomatic. RESULTS: Overall, 53 of 1151 (4.6%) patients showed a CPK increase. Elevations of CPK were deemed to be immunotherapy-related in 31 of 1151 (2.7%) patients. Among them, 12 of 31 (38.7%) patients experienced symptomatic cardiac or neuromuscular irAE, whereas the other 19 of 31 (61.3%) patients remained asymptomatic. In patients with symptomatic irAE, the mean ir-CPK level was higher compared with asymptomatic patients (1271 versus 771 UI/L, P value = 0.02). In the asymptomatic group, all patients experienced a spontaneous resolution of the ir-CPK increase, and none required medical intervention. CONCLUSION: Most patients with immune-related CPK increase remained asymptomatic. The CPK serum increase did not alter the clinical management of asymptomatic patients. The results of this study did not support a significant clinical interest for a systematic routine CPK monitoring in patients amenable to anti-PD-(L)1 immunotherapy.

Continuous Protein Supplementation Reduces Acute Exercise-Induced Stress Markers in Athletes Performing Marathon.

The aim of this study was to determine the changes in endurance performance and metabolic, hormonal, and inflammatory markers induced by endurance stress (marathon race) in a combined strategy of training and dietary protein supplementation. The study was designed as a randomised controlled trial consisting of regular endurance training without and with a daily intake of a soy protein-based supplement over a three-month period in 2 × 15 (10 males and 5 females per group) endurance-trained adults. Body composition (body mass, BMI, and fat mass) was determined, and physical fitness was measured by treadmill ergometry at baseline and after 3 months of intervention; changes in exercise-induced stress and inflammatory markers (CK, myoglobin, interleukin-6, cortisol, and leukocytes) were also determined before and after a marathon competition; eating behaviour was documented before and after intervention by a three-day diet diary. Although no significant influence on endurance performance was observed, the protein supplementation regime reduced the exercise-induced muscle stress response. Furthermore, a protein intake of ≥20% of total energy intake led to a lower-level stress reaction after the marathon race. In conclusion, supplementary protein intake may influence exercise-induced muscle stress reactions by changing cellular metabolism and inflammatory pathways.

Changes in Expressions of HSP27, HSP70, and Soluble Glycoprotein in Heart Failure Rats Complicated with Pulmonary Edema and Correlations with Cardiopulmonary Functions.

The study is aimed at investigating the changes in expressions of heat shock protein 27 (HSP27), HSP70, and soluble glycoprotein (SGP) in heart failure (HF) rats complicated with pulmonary edema and exploring their potential correlations with cardiopulmonary functions. The rat model of HF was established, and the rats were divided into HF model group (model group, n = 15) and normal group (n = 15). After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function indexes were determined, the injury of myocardial tissues was observed via hematoxylin and eosin (HE) staining, and the content of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-alpha (TNF-α) in the blood was measured. The partial pressure of oxygen (PaO2) and oxygenation index (OI) were observed, and the airway resistance and lung compliance were examined. Moreover, quantitative polymerase chain reaction (qPCR) and Western blotting assay were performed to detect the gene and protein expression levels of HSP27, HSP70, and SGP130. The levels of serum creatine kinase (CK), creatine (Cr), and blood urea nitrogen (BUN) were increased markedly in model group (p < 0.05). Model group had notably decreased fractional shortening (FS) and ejection fraction (EF) compared with normal group (p < 0.05), while the opposite results of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were detected. In model group, the content of serum MPO, MMP-9, and TNF-α was raised remarkably (p < 0.05), OI and PaO2 were reduced notably (p < 0.05), the airway resistance was increased (p < 0.05), and the lung compliance was decreased (p < 0.05). Obviously elevated gene and protein expression levels of HSP27, HSP70, and SGP130 were detected in model group (p < 0.05). The expressions of HSP27, HSP70, and SGP130 are increased in HF rats complicated with pulmonary edema, seriously affecting the cardiopulmonary functions of the rats.

Chest pain in a mid-aged woman, not simply myopericarditis: a case report of anti-Ku positive polymyositis.

BACKGROUND: Anti-Ku is a rare antibody which can be positive in some rheumatic diseases and it might be related to cardiac involvement. Polymyositis is an inflammatory myopathy, and its cardiac involvement seldom presents as myopericarditis and anti-Ku positive. CASE PRESENTATION: In this case, we report a mid-aged woman with chest pain, upper limbs weakness and fever unrelated with infection. The diagnosis of this case was unquestionably myopericarditis supported by ECG, cardiac MRI and negative findings in coronary arteries. Diagnosis of polymyositis was further clarified by the evidence of persistently increased CK, degeneration of proximal muscle in MRI, muscular dystrophy with lymphocytes infiltration in muscle biopsy. In the analysis of autoantibodies, we surprisingly discovered positive anti-Ku. Glucocorticoid and mycophenolate mofetil were then prescribed for polymyositis. Patient follow-up indicated remission of both myopericarditis and polymyositis. We finally clarified this rare case as a positive anti-Ku polymyositis with myopericarditis as cardiac involvement. CONCLUSION: This report presents a rare case with anti-Ku positive polymyositis and the cardiac involvement of polymyositis was manifested as myopericarditis. Therefore, positive anti-Ku might explain the myopericarditis as cardiac involvement in polymyositis. More cases and longer duration of follow-up is required for the comprehensive understanding of the disease.