A Rare Treatable Cause of Cardiomyopathy: Primary Carnitine Deficiency.

Introduction: Primary carnitine deficiency (PCD) is a rare autosomal recessive disorder caused by loss of function mutations in the solute carrier family 22 member 5 (SLC22A5) gene that encodes a high-affinity sodium-ion-dependent organic cation transporter protein (OCTN2). Carnitine deficiency can result in acute metabolic decompensation or, in a more insidious presentation, cardiomyopathy. Cardiomyopathy associated with PCD often presents with life-threatening heart failure. This presentation also usually includes skeletal muscle myopathy. Early recognition of this disorder and treatment with carnitine can avoid life-threatening complications related to cardiomyopathy. Case Presentation: Herein, we present a 10-month-old male patient with PCD, which was diagnosed while investigating the etiology of dilated cardiomyopathy and confirmed by molecular genetic analysis. Conclusion: Homozygous c.254_265 insGGCTCGCCACC (p.I89Gfs) pathogenic variant of the SLC22A5 gene was detected. With oral L-carnitine supplementation, the free carnitine level increased up to 14 µmol/L and the symptoms disappeared. LVEF increased by 45-70%. We would like to emphasize that this problem is a combination of the metabolic decompensation and the cardiac phenotypes, which are usually separated to either phenotype.

Examining the impact of a 9-component bundle and the INICC multidimensional approach on catheter-associated urinary tract infection rates in 32 countries across Asia, Eastern Europe, Latin America, and the Middle East.

BACKGROUND: Catheter-Associated Urinary Tract Infections (CAUTIs) frequently occur in the intensive care unit (ICU) and are correlated with a significant burden. METHODS: We implemented a strategy involving a 9-element bundle, education, surveillance of CAUTI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CAUTI rates and performance feedback. This was executed in 299 ICUs across 32 low- and middle-income countries. The dependent variable was CAUTI per 1,000 UC days, assessed at baseline and throughout the intervention, in the second month, third month, 4 to 15 months, 16 to 27 months, and 28 to 39 months. Comparisons were made using a 2-sample t test, and the exposure-outcome relationship was explored using a generalized linear mixed model with a Poisson distribution. RESULTS: Over the course of 978,364 patient days, 150,258 patients utilized 652,053 UC-days. The rates of CAUTI per 1,000 UC days were measured. The rates decreased from 14.89 during the baseline period to 5.51 in the second month (risk ratio [RR] = 0.37; 95% confidence interval [CI] = 0.34-0.39; P < .001), 3.79 in the third month (RR = 0.25; 95% CI = 0.23-0.28; P < .001), 2.98 in the 4 to 15 months (RR = 0.21; 95% CI = 0.18-0.22; P < .001), 1.86 in the 16 to 27 months (RR = 0.12; 95% CI = 0.11-0.14; P < .001), and 1.71 in the 28 to 39 months (RR = 0.11; 95% CI = 0.09-0.13; P < .001). CONCLUSIONS: Our intervention, without substantial costs or additional staffing, achieved an 89% reduction in CAUTI incidence in ICUs across 32 countries, demonstrating feasibility in ICUs of low- and middle-income countries.

New cases of recently described Thauvin-Robinet-Faivre syndrome with a novel homozygous FIBP gene variant.

Thauvin-Robinet-Faivre syndrome (#617107) is a rare autosomal recessive overgrowth syndrome characterized by intellectual disability, facial dysmorphism, macrocephaly, and variable congenital malformations. It is caused by homozygous or compound heterozygous FIBP gene mutations. The FIBP gene is located on the 11q13.1 region and codes the acidic fibroblast growth factor intracellular binding protein, which is involved in the fibroblast growth factor (FGF) signaling pathway. FGF signaling is required for neurogenesis and neuronal precursor proliferation. The FGF controls cell proliferation, differentiation, and migration in embryonic development and in adult life. Overgrowth syndromes consist of a wide spectrum disorders characterized by prenatal and postnatal excess growth in weight and length, often associated malformations, intellectual disability, and neoplastic predisposition. Embryonic tumors are especially common in these syndromes. Thauvin-Robinet-Faivre syndrome is a recently described overgrowth syndrome with typical facial dysmorphic and clinical features. To date, only four patients have been reported with this disorder. Herein, two new cases of Thauvin-Robinet-Faivre syndrome are reported with overgrowth, intellectual disability, typical dysmorphic signs in one dysplastic kidney, and a novel homozygous FIBP gene variant. Exome sequencing analysis showed that both affected siblings share the same homozygous c. 412-3_415dupCAGTTTG FIBP gene variant. Reporting two new cases with this rare autosomal recessive overgrowth syndrome with a novel FIBP gene variant will support and expand the clinical spectrum of Thauvin-Robinet-Faivre syndrome. Also discussed will be the function of FIBP in tumorigenesis and the possible renal tumor susceptibility in heterozygous carriers will be emphasized.

SCYL1 deficiency: A rare entity with challenging neurological manifestations after liver transplantation.

BACKGROUND: Pediatric acute liver failure (PALF) with undetermined etiology is associated with higher liver transplantation and lower spontaneous recovery (transplant-free) rates. The diagnostic odyssey in PALF cases hinders appropriate management and follow-up after liver transplantation. Advances in whole exome sequencing analysis have already been successful at identifying new genetic causes of PALF. CASE PRESENTATION: We report a 17-year-old girl who underwent liver transplantation at the age of 7 months due to acute liver failure and presented later with abnormal neurological manifestations, that is, gait disturbances, dysarthria, and mental retardation that led us to the diagnosis of SCYL1 deficiency. CONCLUSION: PALF cases should be screened for possible underlying genetic disorders. Genetic studies and reanalysis of whole-genome sequencing data may help identify new cases and clarify the genotype-phenotype correlation. SCYL1 deficiency should be suspected in PALF patients who develop neurological involvement after LT. Early diagnosis is vital for proper management of ALF crises in SCYL1 deficiency patients. Despite the reported favorable outcomes of ALF crises in SCYL1 deficiency, liver transplantation decision should be discussed on a case-by-case basis.

A Disseminated Echinococcosis Patient with Five Years Survival from Turkey: A Case Report.

Echinococcosis is a parasitic disease characterized by cysts in especially liver and lung. We report a long-term survival of a 44-year-old female patient with disseminated echinococcal disease involving the brain, lung, liver, spleen, kidney, mediastinum, thyroid gland, parotid gland, pancreas, peritoneum, rectus muscle, pararenal area, left thigh, skin and breast tissue from Turkey in 2016.

Autosomal recessive otospondylo-mega-epiphyseal dysplasia: comprehensive clinical review of a pediatric cohort.

Autosomal recessive otospondylo-mega-epiphyseal dysplasia (OSMEDB) is characterized by short stature with short limbs, dysmorphic facial features, and hearing loss, which is caused by biallelic, loss-of-function, variants in the COL11A2 gene. Geno-phenotypic data from the medical records of eight affected individuals from five unrelated families was abstracted, recorded in an Excel spreadsheet and analyzed using simple frequency analysis. Either short femora or short extremities with or without other ultrasonographic abnormalities were demonstrated in five patients antenatally. The mean height was -2.29 SDS. Pectus deformity, including either chest asymmetry or pectus excavatum, was present in five patients. Bilateral hearing loss was verified in all patients. Severe speech delay and learning disabilities were present in two patients whose deafness was realized after the age of 12 months. Four novel loss-of-function variants in COL11A2 were found in this cohort. We present novel geno-phenotypic findings in a pediatric cohort with OSMEDB. The age of manifestation of short stature was variable, ranging from birth to middle childhood, and the severity of short stature varied even within the same family. Hearing loss may not be evident in the neonatal period and manifest later in OSMEDB. Intermittent hearing tests should be performed for early intervention of neurolinguistic delay and learning disabilities.

Bisphosphonate treatment at spondylo-ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature.

Spondylo-ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo-ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles. Previous reports of bisphosphonate treatment response were variable, whereas a long-term follow-up with bisphosphonate treatment in this case resulted in normalization of vertebral structures. Reporting such cases helps to determine the appropriate genotype-phenotype correlation in patients with XYLT2-related pathogenesis.

Surveillance of hemodialysis related infections: a prospective multicenter study.

As in many countries, there is neither a surveillance system nor a study to reveal the hemodialysis (HD) related infection rates in Turkey. We aimed to investigate the infection rate among HD outpatients and implement CDC's surveillance system. A multicenter prospective surveillance study is performed to investigate the infection rate among HD patients. CDC National Healthcare Safety Network (NHSN) dialysis event (DE) protocol is adopted for definitions and reporting. During April 2016-April 2018, 9 centers reported data. A total of 199 DEs reported in 10,035 patient-months, and the overall DE rate was 1.98 per 100 patient-months. Risk of blood culture positivity is found to be 17.6 times higher when hemodialysis was through a tunneled catheter than through an arteriovenous fistula. DE rate was significantly lower in patients educated about the care of their vascular access site. Staphylococcus aureus was the most causative microorganism among mortal patients. Outcomes of DEs were hospitalization (73%), loss of vascular access (18.2%), and death (7.7%). This first surveillance study revealed the baseline status of HD related infections in Turkey and showed that CDC National Healthcare Safety Network (NHSN) DE surveillance system can be easily implemented even in a high workload dialysis unit and be adopted as a nationwide DE surveillance program.

Efficacy of flecainide in bidirectional ventricular tachycardia and tachycardia-induced cardiomyopathy with Andersen-Tawil syndrome.

Andersen-Tawil syndrome is a rare autosomal dominant genetic or sporadic disorder characterized by periodic paralysis, ventricular arrhythmias and dysmorphic features. Ventricular arrhythmias can include frequent premature ventricular complex, polymorphic ventricular tachycardia, and less frequently bidirectional ventricular tachycardia. Left ventricle function has been reported in only a few individual cases of Andersen-Tawil syndrome. A 14-year-old female patient was referred to our clinic from another center with documented arrhythmia and left ventricular systolic dysfunction. Andersen-Tawil syndrome was suspected and the diagnosis was confirmed after detection of a previously unreported mutation in children. We report the successful use of flecainide in bidirectional ventricular tachycardia and tachycardia-induced cardiomyopathy in a case of Andersen-Tawil syndrome associated with a novel mutation.

Assessment of Pulmonary Arterial Hemodynamic and Vascular Changes by Pulmonary Pulse Transit Time in Patients with Human Immunodeficiency Virus Infection.

INTRODUCTION: Pulmonary arterial hypertension and human immunodeficiency virus (HIV) infection is a well-known association. Pulmonary pulse transit time (pPTT) is a recent echocardiographic marker that might be used for evaluation of pulmonary arterial stiffness (PAS) in patients with HIV infection. We aimed to investigate whether pPTT elevated in patients with HIV infection compared to healthy controls and its association with echocardiographic indices of right ventricular functions. MATERIALS AND METHODS: Fifty HIV (+) patients from infectious disease outpatient clinics and fifty age- and sex-matched HIV (-) healthy volunteers were enrolled in this study. pPTT was measured from pulmonary vein flow velocity as the time interval between the R-wave in the electrocardiography and corresponding peak late systolic was then calculated as the mean from two separate pw-Doppler measurements. RESULTS: pPTT, tricuspid annular peak systolic excursion (TAPSE) and right ventricle fractional area change (FAC) were significantly lower in patients with HIV than control patients (177.1 ± 34.9 vs. 215.7 ± 35.7 msn, P < 0.001; 2.33 ± 0.28 vs. 2.19 ± 0.22, P = 0.039; 45 [4.25] vs. 41.1 [4.0], P = 0.032, respectively). pPTT was positively correlated with FAC, TAPSE and cluster of differentiation 4 count (r = 0.210; P = 0.036, r = 0.256; P = 0.041, r = 0.304; P = 0.044, respectively). CONCLUSION: Our study showed that pPTT, TAPSE, and right ventricle FAC levels were lower in patients with HIV infection. pPTT is an important predictor in patients with HIV expected to develop pulmonary vascular pathology.

Acromesomelic dysplasia-Maroteaux type, nine patients with two novel NPR2 variants.

OBJECTIVES: Acromesomelic dysplasia, type Maroteaux, is an autosomal recessive skeletal dysplasia caused by biallelic loss of function variations of NPR2, which encodes a cartilage regulator C-type natriuretic peptide receptor B. NPR2 variations impair skeletal growth. It is a rare type of dwarfism characterized by shortening of the middle and distal segments of the limbs with spondylar dysplasia. METHODS: We performed detailed clinical and radiological evaluation and sequence analysis for NPR2. RESULTS: Herein, we report nine patients from eight families with two novel NPR2 pathogenic variants. CONCLUSIONS: This study describes typical clinical phenotypes of Maroteaux type acromesomelic dysplasia, and enriches the variant spectrum of NPR2 by reporting one nonsense and one missense novel variant. We emphasize the importance of detailed clinical evaluation before genetic testing in diagnosing rare skeletal disorders.

Role of rapid antibody and ELISA tests in the evaluation of serological response in patients with SARS-CoV-2 PCR positivity.

From 7 to 8 days after the onset of symptoms in COVID-19 infection, the sensitivity of serological tests was found to be higher than that of nucleic acid tests. The aims of this study were to investigate antibody levels in patients with SARS-CoV-2 infection, to examine the relationship between antibody levels and virus load, and to evaluate the performance of 2 different commercial kits. A total of 103 patients with confirmed SARS-CoV-2 infection were included in the study. Antibodies against SARS-CoV-2 in serum samples taken from patients were investigated simultaneously with anti-SARS-CoV-2 IgG and IgA ELISAs (Euroimmun) and COVID-19 (SARS-CoV-2) IgG/IgM (Deep Blue) kits. No positivity was detected with any of the test kits in 18 (17.4%) of the 103 samples. In symptomatic patients, 100% of IgM and IgA tests were found to be positive in the group sampled after 10 days, while 100% of IgG tests were found positive after 20 days. The sensitivity of the Deep Blue COVID-19 IgG antibody kit was calculated as 81.48% and the specificity was 97.96%. While there was no statistically significant difference between the PCR CT and ELISA OD values, a positive correlation was found between the ELISA OD values and the days since the date of symptom initiation. The sensitivity and specificity of the rapid antibody test used in this study were found to be quite high. In conditions where ELISA tests cannot be applied, it is thought that it can give an idea in terms of the presence of antibodies as a simple and fast test. Although ELISA tests are valuable in the diagnosis of COVID-19 during the acute period, they are tests that can be used safely in the diagnosis of previous infections and seroepidemiological studies.

Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome.

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article.

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome.

PURPOSE: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin-Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. METHODS: Clinicians entered clinical data in an extensive web-based survey. RESULTS: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. CONCLUSION: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features.

Risk factors for linezolid-associated thrombocytopenia and negative effect of carbapenem combination.

INTRODUCTION: Linezolid is a synthetic antimicrobial agent with a broad spectrum of activity against virtually all Gram-positive bacteria. Although linezolid is generally well tolerated, the prolonged use of linezolid can lead to myelosuppression, including neutropenia, thrombocytopenia, and anemia. The aim of this study was investigating the risk factors for thrombocytopenia in patients who received linezolid therapy. METHODOLOGY: This retrospective study was performed on patients who received linezolid therapy between July 2007 and December 2017. Thrombocytopenia was defined as either a platelets count of < 100×109/L or a 25% reduction from the baseline platelet count. RESULTS: A total of 371 patients, (198 (53%) male and 173(47%) female were included into the study. Mean duration of therapy was 12.81 ± 5.19 days. Linezolid-induced thrombocytopenia was detected in a total of 111 patients. Using the univariate analysis advanced sex, serum urea concentration, baseline platelet level and low eGFR value were found to be risk factors for linezolid associated thrombocytopenia (p < 0.05). According to a multivariate analysis, patients undergoing carbapenem treatment combination therapy (p = 0.003) and with a baseline platelet level of < 200×109/L (p = 0.00) were found to have a high risk of developing thrombocytopenia. CONCLUSIONS: Several factors may influence of linezolid associated thrombocytopenia. Platelet count should be monitored during therapy and thrombocytopenia should be kept in mind in patients with baseline platelet level of < 200×109/L, low eGFR, linezolid-carbapenem combination therapy.

First cardiac manifestation of hypotonia-cystinuria syndrome.

Hypotonia-cystinuria syndrome is a very rare autosomal recessive contiguous gene deletion syndrome of PREPL and SLC3A1 at 2p21 with neuromuscular and neuroendocrinologic presentation. We report a two-year-six-month-old affected female infant and her five-month-old affected brother with a novel homozygous deletion in SLC3A1 and PREPL gene. Both of siblings had mild facial dysmorphism, hypotonia, feeding problems, failure to thrive, developmental delay. She also had dilated cardiomyopathy which differ from other reported patients. Therefore cardiomyopathy may also be considered one of the features of hypotonia-cystinuria syndrome. With this case report, we present cardiac manifestation of hypotonia-cystinuria syndrome for the first time. Because of two siblings had hyperechogenic bowel in prenatal sonography, it might be a prenatal marker for HCS.

Evaluation of the increase in invasive device associated infections in cardiovascular surgical intensive care unit.

INTRODUCTION: Infections related to the use of invasive instruments leads to the risk of treatment difficulties, prolonged hospitalization, increased health care costs, and increased mortality and morbidity rates. The present study examines the results of an infection surveillance study that showed an increased incidence of infections related to the use of invasive instruments in the cardiovascular surgery intensive care unit of the Ankara Training and Research Hospital and mitigating measures were taken following the surveillance program. METHODOLOGY: Compared with previous surveillance data, an increase was observed in the incidence of infections related to the use of invasive instruments in cardiovascular surgery intensive care unit (CVS-ICU) during the first six months of 2014. A research team was formed comprising one infectious diseases and microbiology specialist, one cardiovascular surgeon, and two infection-control nurses. Patient data was collected. The compliance of the surgeons, nurses, and other health care professionals to the infection control measures was evaluated. RESULTS: The rate of ventilator-associated pneumonia was 8.20% and the rate of catheter-associated urinary tract infection was 4.47% in the CVS-ICU. There were missing or inadvertent practices regarding antibiotic prophylaxis, asepsis and antisepsis and isolation measures in patient preparation and patient care before and after the operations. The rate of inappropriate antibiotic as prolonged use was 72%. CONCLUSIONS: It is one of the basic tasks to take appropriate measures to prevent outbreaks of hospital infections. It is possible to prevent an outbreak of hospital infections only by the accurate analysis of data and establishing strict infection control procedures.