Mean Serum Creatine Research Articles

#1218 Investigating the association of chronic obstructive pulmonary disease with outcomes in patients with non-dialysis dependent chronic kidney disease

Abstract Background and Aims Kidneys and lungs have a strong pathophysiological link. However, studies on the association between chronic conditions involving these two organs, chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), are limited. Nephrologists better understand the pathophysiology and management of acute manifestations of these two organs' dysfunction, i.e., pulmonary-renal syndrome accompanying vasculitis, compared to their chronic alterations. Our study aims to investigate the prevalence and association of COPD with adverse outcomes in patients with CKD (stages 3-5). Method This retrospective observational cohort study was conducted on CKD patients (stages 3-5) enrolled in the Global Collaborative Network (GCN) of the TriNetX research platform between the years 2003 and 2023. TriNetX provides access to anonymized electronic medical records across large healthcare organizations (HCOs). This report includes patients from 112 HCOs with different demographic backgrounds. The study compared outcomes of patients aged 18-80, with and without COPD, in a propensity score matched (PSM) cohort of CKD patients. The characteristics included in the PSM were age, sex, ethnicity, comorbidities (neurological, hematological, cardiovascular, gastroenterological, and endocrine conditions) and baseline serum creatinine. The proportional hazard assumption was tested using the generalized Schoenfeld approach built in the TriNetX platform. A 95% confidence interval (95% CI) was considered evidence of statistical significance throughout the analyses. The Kaplan- Meier (KM) method was used for the survival probability. Statistical significance was defined as p-value < 0.05. Outcome events were included 180 days after the index event (COPD diagnosis) and ended 3650 days after. Results Of the total of 1 045 536 CKD patients, 181 207 had a co-existent diagnosis of COPD (prevalence rate—17.3%). A PSM generated a matched cohort of 174 308 patients each. The mean age of the cohort was 66.7 ± 7.9 years, with a predominance of white ethnicity (65.8%) and an equal male-to-female ratio. 73.1%, 51.5%, 69.6%, 54.1%, and 37.2% had a history of cardiovascular, nervous system, endocrine, gastroenterological, and hematological disease, respectively. The mean serum creatine at baseline was 1.3 ± 1.2 mg/dL. The comparison of differences in the outcomes on follow-up between the matched cohorts is illustrated in Table 1. CKD patients with concomitant COPD had a higher all-cause mortality (17.3% vs 8.7%, p < 0.0001), higher all-cause hospitalizations (14.7% vs 12.7%, p < 0.0001), and higher cardiovascular events. Proportional hazard models showed that COPD is a strong risk factor associated with all-cause mortality (HR: 2.189; 95% CI (2.13-2.22, p < 0.0001)), hospitalizations (HR:1.39; 95% CI (1.36–1.44); p < 0.0001), and other cardiovascular and mental health illness (Table 1). KM chart illustrates the differences in survival probability between the two groups (Log-Rank p < 0.001) (Fig. 1). Conclusion Our ‘real-world data’ findings emphasize that patients with CKD and COPD are a cluster that requires special attention due to poorer outcomes. Given the high frequency of these associations between these two chronic conditions, an improved awareness is warranted among the nephrological community.

Spectrum of non-diabetic kidney diseases in patients with type 2 DM who underwent kidney biopsy in Egypt.

Diabetic kidney disease (DKD) affects 30-40% of diabetic patients. The prevalence of non-diabetic kidney disease (NDKD) in patients with type 2 DM (T2D) in Egypt is unknown. This study aimed to assess the prevalence of NDKD in patients with T2D in Egypt. In this cross-sectional study, we searched the data of patients with T2D who underwent a native kidney biopsy between January 2010 and December 2020 in a kidney pathology laboratory in Egypt. Of 12,006 patients who underwent kidney biopsy, 677 patients had T2D. NDKD was found in 285 patients (42.7%), DKD in 220 patients (33%), and mixed DKD and NDKD in 162 patients (24.3%). The total prevalence of NDKD was 67% in patients with T2D in our study group. Membranous nephropathy (MN) was the most common histopathological disease in patients with NDKD (20.6%) followed by acute tubular injury (ATI) (19.2%) and focal segmental glomerulosclerosis (FSGS) (15.2%). The presence of ATI in kidney biopsy was associated with a significantly higher mean serum creatine level (P<0.001). Minimal change disease was associated with significantly higher proteinuria level (P>0.001). In multivariate analysis, the duration of diabetes was a significant predictor of NDKD, with longer duration decreasing the likelihood of the 'NDKD' outcome. NDKD is prevalent among patients with T2D. Kidney biopsy remains the gold standard for diagnosing NDKD in patients with T2D.

Clinical features and recovery pattern of secondary hypokalaemic paralysis.

Information regarding frequency, details of neurological signs and recovery patterns of patients with secondary hypokalaemic paralysis (HP) is limited. This study aimed to analyse the frequency, aetiology, clinical features and recovery patterns of patients with secondary HP. The clinical and laboratory records of 18 consecutive patients with secondary HP aged ≥ 18years admitted to our hospital between April 2011 and March 2022 were reviewed. Patients with inherited hypokalaemic periodic paralysis were excluded. Of the 18 patients, 16 had a common aetiology: chronic alcoholism, diarrhoea or an imbalanced diet. Initial symptoms, such as fatigue, were often atypical. Three patients had prominent asymmetric limb weakness and four had predominant upper limb weakness. On admission, the mean serum potassium and creatine kinase (CK) levels of the patients were 1.90mmol/L and 4488U/mL, respectively. Ten patients (56%) had decreased potassium levels after admission, despite potassium replacement treatment (rebound hypokalaemia). Twelve patients presented with increased CK levels even after 2-5days (delayed hyperCKaemia). Low serum magnesium levels significantly correlated with rebound hypokalaemia. Secondary HP can be caused by a variety of conditions, but mainly occurs due to lifestyle conditions/disorders. Secondary HP often presents with atypical symptoms, and the initial symptoms can be non-specific. Rebound hypokalaemia and delayed hyperCKaemia are common in secondary HP, despite potassium replacement. As such, careful serial monitoring is needed for patients with secondary HP.

Prediction of the risk of developing end-stage renal diseases in newly diagnosed type 2 diabetes mellitus using artificial intelligence algorithms

ObjectivesType 2 diabetes mellitus (T2DM) imposes a great burden on healthcare systems, and these patients experience higher long-term risks for developing end-stage renal disease (ESRD). Managing diabetic nephropathy becomes more challenging when kidney function starts declining. Therefore, developing predictive models for the risk of developing ESRD in newly diagnosed T2DM patients may be helpful in clinical settings.MethodsWe established machine learning models constructed from a subset of clinical features collected from 53,477 newly diagnosed T2DM patients from January 2008 to December 2018 and then selected the best model. The cohort was divided, with 70% and 30% of patients randomly assigned to the training and testing sets, respectively.ResultsThe discriminative ability of our machine learning models, including logistic regression, extra tree classifier, random forest, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine were evaluated across the cohort. XGBoost yielded the highest area under the receiver operating characteristic curve (AUC) of 0.953, followed by extra tree and GBDT, with AUC values of 0.952 and 0.938 on the testing dataset. The SHapley Additive explanation summary plot in the XGBoost model illustrated that the top five important features included baseline serum creatinine, mean serum creatine within 1 year before the diagnosis of T2DM, high-sensitivity C-reactive protein, spot urine protein-to-creatinine ratio and female gender.ConclusionsBecause our machine learning prediction models were based on routinely collected clinical features, they can be used as risk assessment tools for developing ESRD. By identifying high-risk patients, intervention strategies may be provided at an early stage.

Mean Serum Creatine Kinase among Organophosphate Poisoning Cases in a Tertiary Care Centre: A Descriptive Cross-sectional Study

Major cases of poisoning are associated with organophosphates. Cholinergic effects and an intermediate phase seen with organophosphate poisoning may implicate myopathy. Creatine kinase is a marker of muscle tissue damage. This study aimed to find out the mean serum creatine kinase among organophosphate poisoning cases in a tertiary care centre. A descriptive cross-sectional study was carried out among organophosphate poisoning cases in a tertiary care hospital from 13 October 2017 to 30 March 2018. Ethical approval was taken from the Institutional Review Committee [Reference number: 117(6-11-E) 2/074/075]. Blood samples were assayed for serum acetylcholinesterase in the pharmacology laboratory and for serum creatine kinase and lactate dehydrogenase in the biochemistry laboratory. Low serum acetylcholinesterase was taken as the basis for the establishment of organophosphate poisoning. A convenience sampling technique was used. Point estimate and 95% Confidence Interval were calculated. Among 103 organophosphate poisoning cases, the mean serum creatine kinase was 931.35±446.60 IU/l (845.10-1017.60, 95% Confidence Interval). The mean serum creatine kinase level among organophosphate poisoning cases was higher than in other studies done in similar settings. acetylcholinesterase; creatine kinase; organophosphate poisoning; rhabdomyolysis.

Deciding When to Intubate a COVID-19 Patient.

The SARS-CoV-2 pandemic is one of the most significant challenges for healthcare providers, particularly in the critical care setting. The timing of intubation in COVID-19 patients seems to be challenging. Therefore, we aimed to investigate how it may have a survival benefit, and we determined which clinical characteristics were associated with outcomes. This cross-sectional study was conducted in the Imam Khomeini Hospital Complex. We randomly selected patients admitted to intensive care units and, based on intubation status, categorized them into three subgroups (early, late, and not intubated). Early intubation is defined as intubation within 48 hours of ICU admission, and late intubation is defined as intubation after 48 hours of ICU admission. Early-intubated patients were more likely to have dyspnea than late-intubated patients, and late-intubated patients had a higher mean heart rate than early-intubated patients. The neutrophil/lymphocyte ratio was significantly (P < 0.05) lower in not-intubated patients than in other patients. There was no difference in NLR between early- and late-intubated patients. Mean serum creatine phosphokinase and troponin I levels were higher in late-intubated patients than in early- and not-intubated patients. Early-intubated patients had a lower ROX index than late-intubated patients. Patients with higher scores of APACHE 2, respiratory rates, and neutrophil to lymphocyte ratio were more likely to be intubated. Increasing APACHE and SOFA scores were associated with decreased odds of survival. There were no statistically significant differences in total mortality between early- and late-intubated patients. APACHE 2 scores, NLR, RR, and history of ischemic heart disease are some of the appropriate predictors of intubation. Higher respiratory rates (tachypnea) can be an indicator of early intubation. The ROX index is one of the most sensitive and capable tools for predicting intubation. Intubation status is a potent predictor of in-hospital mortality.

The Frequency of Diabetic Macular Edema and its Systemic Risk Factors: A Cross-Sectional Study

Objective: The goal of this research was to use optical coherence tomography to assess the prevalence of diabetic macular edoema and to determine the impact of systemic results and risk factors on the progression of DME. Material and Methods: This cross-sectional research was carried out at the Department of Ophthalmology, Chandka Medical College &amp; Shaheed Mohtarma Benazir Bhutto Medical University Larkana. Patients were asked to fill out questionnaires about their health and lifestyle habits like smoking and alcohol consumption as well as their hemoglobin A1C and lipid profiles, as well as the duration of their diabetes, and the type of diabetes they had. There was an investigation into the link between systemic findings and DME Results: A total of 150 cases met the study's eligibility requirements. Males comprised 84 (56%) of the 150 participants, while females comprised 66 (44%). Sixty-five patients (43.33%) tested positive for DME, while 85 patients (56.66%) tested positive for DR. DME participants had HbA1c levels of 9.39 ± 1.67percent, whereas participants without DME had levels of 7.02 ± 3.23 percent and p=0.326; but no connection was found between the two measurements. There was a statistically significant difference between the mean serum creatine concentrations in cases with and without DME (p=0.011). For DME, a statistically significant difference (P-value = 0.001) was found between normal-albuminuric, microalbuminuric, and macroalbuminuric patients. Using the DME frequency in phakic and pseudophakic eyes as a guide, figure 2 below illustrates the results. Conclusions: Diabetic macular edema was seen in 43.33% of cases in the current study. An OCT-based study revealed that DME is common in Larkana Sindh. Regulating DME risk factors can help prevent or limit the development of DME, and treatment response may be improved. Keywords: Systemic risk factors, Diabetic macular edema, Optical coherence tomography,

Safety of perioperative period in robot-assisted atrial septal defect repair under hyperkalemic arrest

BackgroundVarious attempts have been made to meet patient desires, especially among younger and otherwise healthy individuals, for cosmetically satisfying incision with atrial septal defect (ASD) repair. One of procedures was a robotic-assisted totally endoscopic ASD repair via only two ports under hyperkalemic arrest without aortic cross-clamping. This study investigated perioperative management and safety for robotic-assisted total endoscopic ASD repair surgery under hyperkalemic arrest.MethodsWe retrospectively reviewed perioperative management of thirty patients who underwent total endoscopic robot-assisted ASD repair under hyperkalemic arrest. All procedures were performed under general anesthesia using robotic-assisted total endoscopic for ASD repair via two or three ports under hyperkalemic arrest without aortic cross-clamping.ResultsA total of 30 patients (mean age 45 ± 17 years, 8 male, 22 female) underwent successful ASD repair with the total endoscopic robotic-assisted procedures under hyperkalemic arrest.Hyperkalemic arrest was achieved and maintained by intravenous administration of mean potassium dose of 91±32 mEq (1.4±0.6 mEq/kg) with the lowest bladder temperature was 31.9±1.4 °C during hyperkalemic arrest.In all cases, serum potassium concentration was <5.0 mEq/L after weaning from cardiopulmonary bypass, although two cases who developed hyperkalemia >6 mEq/L after operation. At other time points, no patient exceeded 6 mEq/L of serum potassium concentration. At admission to the intensive care unit, mean serum creatine phosphokinase-MB level was 32±7mg/dL. There were no cases of arrhythmia or other cardiac complications during recovery.ConclusionsPerioperative management of robotic-assisted total endoscopic ASD repair under hyperkalemic arrest is safe and is not associated with fatal arrhythmia due to hyperkalemia.

Emergency retroperitoneal laparoscopic partial nephrectomy for ruptured renal angiomyolipomas: a retrospective single-center series of 15 cases

BackgroundTo assess the safety, tumor control and renal function preservation of the emergency retroperitoneal laparoscopic partial nephrectomy (LPN) for ruptured renal angiomyolipoma (AML) and summarize our single-center initial experience.MethodsWe performed a retrospective analysis of 15 patients pathologically confirmed renal AML treated with emergency retroperitoneal LPN between January 2016 and May 2019. The patient demographics, operation time, blood loss, transfusion requirements, complications and other surgical parameters were analyzed. Follow-up was performed by serum creatinine and imaging modalities.ResultsFifteen patients were performed with emergency LPN with the median age 41.6 years. The mean size of the renal AMLs was 7.8 cm. The mean size of the retroperitoneal hematomas was 8.5 cm. All the emergency surgeries were performed successfully without any conversion to nephrectomy or open surgery. The mean operative time was 101 min. The mean warm ischemia time was 28 min. The mean estimated blood loss was 311 ml. Five patients required intraoperative blood transfusion (33.3%, 5/15). The mean transfused RBC was 4 U (range 2-6 U), and the mean transfused plasma was 200 ml (range 200-400 ml). The mean drainage duration was 3 days (range 2–5 days). The mean postoperative hospitalization was 4.7 days. No patients experienced intraoperative complications. The mean serum creatine was slightly higher after surgery (53.1 vs. 55.9 μmol/L). One patient had postoperative perirenal fluid collection. No patients needed dialysis. No recurrence was observed in the patients at the median follow-up of 24.1 months.ConclusionsOur initial experience shows that the emergency retroperitoneal LPN is a safe, minimally invasive procedure for emergency patients with ruptured renal AMLs. It could be considered as an effective alternative to renal artery embolization in selected emergency patients.

The Evaluation of Benign Acute Childhood Myositis by Ultrasound Elastography

Objective: Herein, we aimed to determine the diagnostic contribution of ultrasound elastography (UE) technique to the assessment of muscle stiffness in pediatric patients with myositis.&#x0D; Material and Methods: This study enrolled 16 patients who presented to our hospital’s Pediatric Neurology Outpatient Clinic with the complaint of inability to walk and who had a clinical presentation of benign acute childhood myositis (BACM). The patients were referred to the Radiology Department to undergo muscle ultrasonography (USG), where they underwent UE of the gastrocnemius muscle (GCM).&#x0D; Results: Children with myositis and healthy children are similar age (7.06 ± 1.52 year (5–11) vs. 7.00 ± 1.59 year (5–11) year) (P: 0.908) and body mass index (BMI) (20.04 ± 1.58 (18.6–24.2) vs. 22.08 ± 1.43 (19.9–24.4) (P: 0.946). The mean serum creatine kinase (CK) was measured as 1520.3 ± 1163.6 U/L (min: 456, max:4100) in children with myositis. In the children with myositis, the thickness of the medial and lateral GCM increased compared with that in control group (medial; 18.15 ± 3.02 mm vs 13.10 ± 2.26 mm, p&lt;0.001, lateral; 13.51 ± 3.07 mm vs 9.34 ± 1.86 mm, p&lt;0.001). The medial and lateral GCM ratio in group 1 was slight bigger than that in group 2 (medial; 1.10 ± 0.37 vs 1.00 ± 0.34, p: 0.274, lateral; 1.22 ± 0.44 vs 1.10 ± 0.29, p: 0.243). GCM strain values were mildly elevated in patients with myositis compared to controls.&#x0D; Conclusion: In the children with myositis, the thickness of the medial and lateral GCM increased compared with that in control group. GCM strain ratio values were slightly higher in myositis patients compared to the control group. We think that the increase in muscle thickness values is mainly secondary to the edema seen in myositis. In addition, UE is a clinically applicable quantitative analysis for changes in myositis.

P.258 - Clinical, radiological, and genetic survey of patients with muscle–eye–brain disease caused by mutations in POMGNT1

BACKGROUND: To evaluate clinical, genetic, and radiologic features of our patients with muscle-eye-brain disease. METHODS: The data of patients who were diagnosed with muscle-eye-brain disease from a cohort of patients with congenital muscular dystrophy in the Division of Pediatric Neurology of Dokuz Eylul University School of Medicine and Gaziantep Children’s Hospital between 2005 and 2013 were analyzed retrospectively. RESULTS: From a cohort of 34 patients with congenital muscular dystrophy, 12 patients from 10 families were diagnosed with muscle-eyebrain disease. The mean age of the patients was 9 � 5.5 years (2-19 years). Mean serum creatine kinase value was 2485.80 � 1308.54 IU/L (700-4267 IU/L). All patients presented with muscular hypotonia at birth followed by varying degrees of spasticity and exaggerated deep tendon reflexes in later stages of life. Three patients were able to walk. The most common ophthalmologic and radiologic abnormalities were cataracts, retinal detachment, periventricular white matter abnormalities, ventriculomegaly, pontocerebellar hypoplasia, and multiple cerebellar cysts. All of the patients had mutations in the POMGNT1 gene. The most common mutation detected in 66% of patients was c.1814 G > A (p.R605H). Two novel mutations were identified. CONCLUSIONS: We suggest that muscle-eye-brain disease is a relatively common muscular dystrophy in Turkey. It should be suspected in patients with muscular hypotonia, increased creatine kinase, and structural eye and brain abnormalities. The c.1814 G > A mutation in exon 21 of the POMGNT1 gene is apparently a common mutation in the Turkish population. Individuals with this mutation show classical features of muscle-eye-brain disease, but others may exhibit a milder phenotype and retain the ability to walk independently. Congenital muscular dystrophy patients from Turkey carrying the clinical and radiologic features of muscle-eye-brain disease should be evaluated for mutations in POMGNT1 gene.

Magnetic resonance imaging changes of thigh muscles in myopathy with antibodies to signal recognition particle.

The aim of this study was to evaluate muscle MRI changes and the role of MRI in monitoring therapy in patients with myopathy associated with antibodies to signal recognition particle (anti-SRP myopathy). We identified 12 patients with anti-SRP myopathy [6 females and 6 males; mean age of onset 38.5 years (s.d. 12.4), mean duration 22.8 months (s.d. 20.6). The main symptoms were proximal limb muscle weakness. Mean serum creatine kinase levels were moderately increased. Muscle biopsies revealed necrotizing myopathy in all patients, with obvious connective tissue proliferation in five patients and a single focus of lymphocytic infiltration in the endomysium in one. The myositis disease activity assessment (MYOACT) visual analogue scales scores were assessed. Muscle MRI was performed through the thighs. All patients were treated with corticosteroids and other immunosuppressive drugs. MRI revealed fatty infiltration and oedema in the thigh muscles of all 12 patients. Prominent fatty infiltration was present in 4 of the 12 patients. The hamstrings and adductor magnus were the most severely infiltrated and the quadriceps femoris the least. Obvious oedema was observed in 10 of the 12 patients, the most severely affected muscles being the vastus lateralis, rectus femoris, biceps femoris and adductor magnus, with relative sparing of the vastus intermedius. The degree of oedema was not correlated with creatine kinase levels or MYOACT scores. The four patients with striking fatty infiltration were refractory to therapy. MRI of the thigh muscles shows a distinct pattern of oedema and fatty infiltration and can be used to monitor the treatment of patients with anti-SRP myopathy.

G.P.74: Anti-Signal Recognition Particle associated myopathy in a multiethnic Malaysian population

Anti-Signal Recognition Particle (SRP) myopathy is a complement dependent antibody-mediated necrotising myopathy which is often clinically more severe and require longer and more aggressive immunosuppressive treatment. We describe a series of Malaysian patients with anti-SRP myopathy. Of 30 patients with idiopathic inflammatory myopathy, seen prospectively at the University of Malaya Medical Centre, Kuala Lumpur between 2012 and 2014, eight (26.7%) had positive anti-SRP antibodies. All patients were female, of whom four were ethnic Malays and four, ethnic Chinese. Their mean age of disease onset was 37years (range 24–60years). All presented with progressive severe proximal muscle weakness. Mean serum creatine kinase at presentation was 4994u/L (range 385–14,000iu/L). Muscle histopathology showed muscle fibre necrosis with variable regenerative features. Inflammation ranged from minimal to severe infiltration of lymphocytes in seven patients and in one patient, there was marked variation of fibre size with interstitial fibrosis, morphological features similar to that of muscular dystrophy. All patients responded only partially to corticosteroids and other immunosuppressive agents including methotrexate, mycophenolate mofetil, azathioprine and IVIG. Rituximab was given to one patient but with minimal improvement. Other associated autoantibodies found included anti Ro-52 in 50% and anti PM-Scl75 and anti PL-12 in 25% respectively. None had associated interstitial lung disease nor underlying malignancy. In prospective series inflammatory myopathy patients seen at a tertiary Malaysian hospital, anti-SRP myopathy was seen a quarter of the patients. The clinical picture was similar to anti-SRP myopathy reported from other populations.

Microendoscopy-Assisted Muscle-Preserving Interlaminar Decompression for Lumbar Spinal Stenosis

A retrospective review of data collected prospectively on patients who underwent microendoscopy-assisted muscle-preserving interlaminar decompression (MILD) for lumbar spinal stenosis. To evaluate the clinical results including surgical invasiveness and reduction rate of facet joint with a follow-up of more than 3 years. Hatta et al reported microscopic posterior decompression procedure, MILD for lumbar spinal stenosis with reference to the cervical central approach put forth by Shiraishi. Mikami et al applied spinal microendoscopy to MILD procedure (microendoscopy-assisted MILD). One hundred five consecutive patients, who underwent microendoscopy-assisted MILD, participated in this study. Operative time, blood loss, visual analogue scale (VAS), serum creatine kinase and C-reactive protein, surgical complications, reduction rate of the facet joint, Japanese Orthopaedic Association score, and Short-Form 36 were evaluated. The operative time was 99.3 minutes and the intraoperative bleeding was 15.7 mL on average. The mean VAS score to assess surgical site pain was 20.6 mm on postoperative day 1. The mean serum creatine kinase on postoperative day 1 and C-reactive protein on postoperative day 3 were 145.4 IU/L and 2.7 mg/dL, respectively. Surgical complications were identified in 2 cases, cauda equina injury and dural tear. The mean reduction rate of the facet joint was 3%. The follow-up rate was 83.3% and the mean follow-up period was 52.7 months. The Japanese Orthopaedic Association score improved significantly from 14.8 to 23.7 points on average. Significant improvements in Short-Form 36 were observed in all subscales except in General Health. Revision surgical procedures were performed in 8 cases at the operated level including 4 of juxtafacet cyst, 3 of disc herniation, and 1 of insufficient decompression. Microendoscopy-assisted MILD is a minimally invasive procedure and favorable clinical results can be expected for lumbar spinal stenosis. 4.

Clinical, Radiological, and Genetic Survey of Patients With Muscle-Eye-Brain Disease Caused by Mutations in POMGNT1

BackgroundTo evaluate clinical, genetic, and radiologic features of our patients with muscle-eye-brain disease. MethodsThe data of patients who were diagnosed with muscle-eye-brain disease from a cohort of patients with congenital muscular dystrophy in the Division of Pediatric Neurology of Dokuz Eylül University School of Medicine and Gaziantep Children's Hospital between 2005 and 2013 were analyzed retrospectively. ResultsFrom a cohort of 34 patients with congenital muscular dystrophy, 12 patients from 10 families were diagnosed with muscle-eye-brain disease. The mean age of the patients was 9 ± 5.5 years (2-19 years). Mean serum creatine kinase value was 2485.80 ± 1308.54 IU/L (700-4267 IU/L). All patients presented with muscular hypotonia at birth followed by varying degrees of spasticity and exaggerated deep tendon reflexes in later stages of life. Three patients were able to walk. The most common ophthalmologic and radiologic abnormalities were cataracts, retinal detachment, periventricular white matter abnormalities, ventriculomegaly, pontocerebellar hypoplasia, and multiple cerebellar cysts. All of the patients had mutations in the POMGNT1 gene. The most common mutation detected in 66% of patients was c.1814 G > A (p.R605H). Two novel mutations were identified. ConclusionsWe suggest that muscle-eye-brain disease is a relatively common muscular dystrophy in Turkey. It should be suspected in patients with muscular hypotonia, increased creatine kinase, and structural eye and brain abnormalities. The c.1814 G > A mutation in exon 21 of the POMGNT1 gene is apparently a common mutation in the Turkish population. Individuals with this mutation show classical features of muscle-eye-brain disease, but others may exhibit a milder phenotype and retain the ability to walk independently. Congenital muscular dystrophy patients from Turkey carrying the clinical and radiologic features of muscle-eye-brain disease should be evaluated for mutations in POMGNT1 gene.

Long-term Engraftment of Multipotent Mesenchymal Stromal Cells That Differentiate to Form Myogenic Cells in Dogs With Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an incurable genetic disease with early mortality. Multipotent mesenchymal stromal cells (MSCs) are of interest because of their ability to differentiate to form myogenic cells in situ. In the present study, methods were developed to expand cultures of MSCs and to promote the myogenic differentiation of these cells, which were then used in a new approach for the treatment of DMD. MSC cultures enriched in CD271(+) cells grew better than CD271-depleted cultures. The transduction of CD271(+) MSCs with MyoD caused myogenic differentiation in vitro and the formation of myotubes expressing late myogenic markers. CD271(+) MSCs in the myogenic cell lineage transplanted into dog leukocyte antigen (DLA)-identical dogs formed clusters of muscle-like tissue. Intra-arterial injection of the CD271(+) MSCs resulted in engraftment at the site of the cardiotoxin (CTX)-injured muscle. Dogs affected by X-linked muscular dystrophy in Japan (CXMD(J)) treated with an intramuscular injection of CD271(+) MSCs similarly developed muscle-like tissue within 8-12 weeks in the absence of immunosuppression. In the newly formed tissues, developmental myosin heavy chain (dMyHC) and dystrophin were upregulated. These findings demonstrate that a cell transplantation strategy using CD271(+) MSCs may offer a promising treatment approach for patients with DMD.

Therapeutic effect of fucoidan‐stimulated endothelial colony‐forming cells in peripheral ischemia

Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony-forming cells (ECFC) to adopt an angiogenic phenotype in vitro. We evaluated the effect of fucoidan on vasculogenesis induced by ECFC in vivo. We used a murine hindlimb ischemia model to probe the synergic role of fucoidan-treatment and ECFC infusion during tissue repair. We found that exposure of ECFC to fucoidan prior to their intravenous injection improved residual muscle blood flow and increased collateral vessel formation. Necrosis of ischemic tissue was significantly reduced on day 14, to 12.1% of the gastronecmius cross-sectional surface area compared with 40.1% in animals injected with untreated-ECFC. ECFC stimulation with fucoidan caused a rapid increase in cell adhesion to activated endothelium in flow conditions, and enhanced transendothelial extravasation. Fucoidan-stimulated ECFC were resistant to shear stresses of up to 21 dyn cm(-2). Direct binding assays showed strong interaction of fucoidan with displaceable binding sites on the ECFC membrane. Bolus intramuscular administration of fucoidan 1 day after surgery reduces rhabdomyolysis. Mice injected with fucoidan (15 mg kg(-1)) had significantly lower mean serum creatine phosphokinase (CPK) activity than control animals. This CPK reduction was correlated with muscle preservation against necrosis (P < 0.001). Fucoidan greatly increases ECFC-mediated angiogenesis in vivo. Its angiogenic effect would be due in part to its transportation to the ischemic site and its release after displacement by proteoglycans present in the extracellular matrix. The use of ECFC and fucoidan together, will be an efficient angiogenesis strategy to provide therapeutic neovascularization.

Clinical features and recovery patterns of acquired non-thyrotoxic hypokalemic paralysis

Objective To report the clinical features and recovery patterns of patients with non-thyrotoxic acquired hypokalemic paralysis. Methods The clinical and laboratory records of 11 consecutive patients with acquired non-thyrotoxic hypokalemic paralysis were reviewed and compared with those of 3 patients with thyrotoxic periodic paralysis (TPP). The causes of potassium wasting were diarrhea (n = 4), alcohol abuse (n = 2), pseudoaldosteronism (n = 2), primary aldosteronism (n = 1), distal renal tubular acidosis associated with Sjögren's syndrome (n = 1) and an unknown cause (n = 1). Results Three of the 11 patients had prominently asymmetric limb weakness, and 2 had predominant upper limb weakness. On admission, mean serum potassium and creatine kinase (CK) levels of patients with acquired hypokalemic paralysis on admission were 1.8 mEq/L and 4,075 U/mL, respectively, and the mean duration between admission and independent walking was 6.8 days (range, 2–31 days). Despite clinical recovery, 10 patients still presented with increased CK levels after several days (mean of maximum levels, 10,519 U/mL). In addition, normalization of serum potassium levels in patients with acquired hypokalemic paralysis patients was much slower compared to that in patients with TPP. One patient with acquired hypokalemic paralysis developed ventricular fibrillation, whereas all 3 patients with TPP had symmetric proximal and lower limb-dominant weakness and exhibited complete recovery from paralysis as well as normalized serum potassium levels within 24 h. Conclusions In patients with acquired non-thyrotoxic hypokalemic paralysis, asymmetric or upper limb-dominant weakness of the extremities is observed. Despite clinical improvement after treatment, normalization of serum potassium and CK levels is often delayed, and therefore, careful monitoring for cardiac and renal complications is required.

Reduced postoperative wound pain after lumbar spinous process–splitting laminectomy for lumbar canal stenosis: a randomized controlled study

to reduce intraoperative damage to the posterior supporting structures of the lumbar spine during decompressive surgery for lumbar canal stenosis (LCS), lumbar spinous process-splitting laminectomy (LSPSL or split laminectomy) was developed. This prospective, randomized, controlled study was conducted to clarify whether the split laminectomy decreases acute postoperative wound pain compared with conventional laminectomy. forty-one patients with LCS were enrolled in this study. The patients were randomly assigned to either the LSPSL group (22 patients) or the conventional laminectomy group (19 patients). Questionnaires regarding wound pain (intensity, depth, and duration) and activities of daily living (ADL) were administered at postoperative days (PODs) 3 and 7. Additionally, the authors evaluated the pre- and postoperative serum levels of C-reactive protein and creatine phosphokinase, the amount of pain analgesics used during a 3-day postoperative period, and the muscle atrophy rate measured on 1-month postsurgical MR images. data obtained in patients in the LSPSL group and in 16 patients in the conventional laminectomy group were analyzed. The mean visual analog scale for wound pain on POD 7 was significantly lower in the LSPSL group (16 ± 17 mm vs 34 ± 31 mm, respectively; p = 0.04). The mean depth-of-pain scores on POD 7 were significantly lower in the LSPSL group than in the conventional group (0.9 ± 0.6 vs 1.7 ± 0.8, respectively; p = 0.013). On POD 3, the mean serum creatine phosphokinase level was significantly lower in the LSPSL group (126 ± 93 U/L) than in the other group (207 ± 150 U/L) (p = 0.02); on POD 7, the mean serum C-reactive protein level was significantly lower in the LSPSL group (1.1 ± 0.6 mg/dl) than in the conventional laminectomy group (1.9 ± 1.5 mg/dl) (p = 0.04). The number of pain analgesics taken during the 3-day postoperative period was lower in the LSPSL group than in the conventional laminectomy group (1.7 ± 1.3 tablets vs 2.3 ± 2.4 tablets, respectively; p = 0.22). The mean muscle atrophy rate was also significantly lower in the LSPSL group (24% ± 15% vs 43% ± 22%; p = 0.004). lumbar spinous process-splitting laminectomy for the treatment of LCS reduced acute postoperative wound pain and prevented postoperative muscle atrophy compared with conventional laminectomy, possibly because of minimized damage to the paraspinal muscles.

YPSP01-10 - Blood cholesterol and serum creatine kinase levels in violent psychiatric patients

ObjectivesIndividuals with severe mental illness display significantly higher rates of violence than general population. In previous reports, violent behavior was found associated with mean serum creatine kinase activity (MSCK) and with reduced levels of total blood cholesterol (LTBC). The aim of study was to assess an association between MSCK and LTBC in two groups of male violent forensic psychiatric offenders.MethodsThe study population was 256 offenders from the closed ward, of whom 214 were schizophrenia patients and 42 were patients with personality disorders. The prevalence of murderers was 21.7% in the schizophrenia group and 21.3% in the group with personality disorders.ResultsSchizophrenia patients had significantly higher MSCK and LDH levels then subjects with personality disorders. There were no significant between-groups differences on other biological parameters. No significant differences on these parameters were found between murderers and nonmurderers in both groups. In the overall sample, significant negative correlation was found between MSCK activity and total cholesterol levels. Similar correlation pattern was found in the schizophrenia group, but not in subjects with personality disorders.ConclusionsThe results show for the first time identifiable MSCK/LTBC pattern in violent schizophrenia patients but not in subjects with personality disorders. It is possible that different character of association between MSCK and LTBC in two groups of violent forensic psychiatric offenders (schizophrenia patients vs. subjects with personality disorders) reflects different biological origins of violent behavior. Further investigation of described MSCK/LTBC pattern in larger population of forensic and non-forensic, psychiatric and non-psychiatric subjects, is warranted.