Variants in HNRNPDL and SETX Not Necessarily Indicate Familial Amyotrophic Lateral Sclerosis or Limb Girdle Muscular Dystrophy 1G in Acute Muscular Respiratory Failure.

Genetic work-up is useful for the identification of a primary myopathy. However, even sophisticated genetic methods may fail to detect the underlying cause of myopathy as in the following case. The patient is a 52-year-old female with a history of epilepsy, arterial hypertension, atrial flutter requiring cardioversion, ablation, and anticoagulation, coronary heart disease, hyperlipidemia, and hyper-CKemia. At age 52 years, she was referred for heart failure due to ischemic cardiomyopathy requiring appropriate medication and implantation of an ICD. During hospitalization she developed acute muscular respiratory failure requiring mechanical ventilation. Genetic panels for myopathy, neuropathy, and cardiomyopathy revealed variants of unknown significance in the HNRNPDL and SETX genes respectively. Clinical presentation and muscle biopsy, however, suggested metabolic myopathy. Acute muscular respiratory failure may require traditional diagnostic work-up for primary myopathy and long-term invasive and non-invasive ventilation. Panel investigations not necessarily lead to a conclusive diagnosis. The multisystem nature of the condition rather suggests a metabolic defect than LGMD-1G or fALS as genetic findings suggested.

Indications for and outcome in patients with the wearable cardioverter-defibrillator in a nurse-based training programme: results of the Austrian WCD Registry.

BACKGROUND: The wearable cardioverter-defibrillator is a treatment option for patients at temporarily high risk of sudden cardiac death or in whom implantation of a cardioverter-defibrillator is temporarily not possible. OBJECTIVES: The aim of this study was to provide real-world data on patients receiving this therapy in a nurse-based wearable cardioverter-defibrillator training programme. METHODS: A registry including all patients prescribed with a wearable cardioverter-defibrillator in Austria between 2010 and 2016. Overall, 448 patients received a wearable cardioverter-defibrillator in 48 centres. Patients received structured nurse-based wearable cardioverter-defibrillator educational initial training followed by remote monitoring. RESULTS: Main indications were: severe non-ischaemic cardiomyopathy (21%); recent myocardial infarction and percutaneous coronary intervention (20%); and stable coronary artery disease with percutaneous coronary intervention/coronary artery bypass grafting (14%). Eleven patients (2.5%) received 22 appropriate wearable cardioverter-defibrillator shocks. Two patients (0.4%) received three inappropriate shocks. The risk of sudden cardiac death varied between different aetiologies. Eight out of 11 (73%) patients received their first wearable cardioverter-defibrillator shock within 30 days. The main reasons for termination of the wearable cardioverter-defibrillator therapy were implantable cardioverter-defibrillator implantation (55.5%) and improvement of left ventricular ejection fraction to more than 35% (33%). CONCLUSION: The wearable cardioverter-defibrillator is an effective and safe treatment option in patients at either transiently elevated risk of ventricular tachycardia/ventricular fibrillation or mandated postponed implantable cardioverter-defibrillator implantation, with a 2.5% shock rate over a median 54 days wearable cardioverter-defibrillator treatment period. However, both the wearable cardioverter-defibrillator shock rate and implantable cardioverter-defibrillator implantation rate vary widely depending on the wearable cardioverter-defibrillator indication. Nurse-based wearable cardioverter-defibrillator training is associated with high patient adherence, with a median wearing duration per day of 23.5 (1-24) hours.

Phenytoin-induced choreoathetosis after serial seizures due to traumatic brain injury and chronic alcoholism.

Intravenous phenytoin (PHT) for suspected seizures may trigger severe choreoathetosis. Discontinuation of PHT results in immediate and complete resolution of hyperkinesias. Co-medication with valproic acid, levetiracetam, tranquilisers, and anesthetics or alcohol presumably do not modify this adverse effect of PHT. Choreoathetosis can be easily misinterpreted as seizures.

Takotsubo as Initial Manifestation of Non-Myopathic Cardiomyopathy Due to the Titin Variant c.1489G > T.

Background: Whether patients with subclinical cardiomyopathy (CMP) are more prone to experience Takotsubo syndrome (TTS) than patients without CMP, is unknown. We present a patient with TTS as the initial manifestation of a hitherto unrecognized genetic CMP. Method: case report. Results: At age 55 after the unexpected death of her father, a now 61-year-old female had developed precordial pressure. Work-up revealed moderately reduced systolic function, dyskinesia of the interventricular septum, and indications for a TTS. Coronary angiography was normal but ventriculography showed TTS. Cardiac MRI confirmed reduced systolic function and TTS. TTS resolved without treatment and sequelae. At age 57 atrial fibrillation was recorded. After deterioration of systolic function at age 59 dilated CMP was diagnosed. Despite application of levosimendan, sacubitril, valsartan, and ivabradine, complete remission could not be achieved. Upon genetic work-up by means of a gene panel, the heterozygous mutation c.1489G > T (p. E497X) in exon 9 of the titin gene was detected and made responsible for the phenotype. Neurological work-up precluded involvement of the skeletal muscles. The further course was complicated by ventricular arrhythmias, requiring implantation of an implantable cardioverter defibrillator (ICD). CONCLUSIONS: previously subclinical CMP may initially manifest as TTS. Since patients with titin CMP are at risk of developing ventricular arrhythmias and thus to experience sudden cardiac death, appropriate anti-arrhythmic therapy needs to be established.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography May Exclude Malignancy in Sonographically Suspicious and Scintigraphically Hypofunctional Thyroid Nodules and Reduce Unnecessary Thyroid Surgeries.

BACKGROUND: The aim of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful in the further characterization of sonographically suspicious and scintigraphically hypofunctional thyroid nodules. METHODS: Sixty-five patients with sonographically suspicious thyroid nodules that were hypofunctional on 99m-Tc-pertechnetate scintigraphy (diameter >1 cm) were retrospectively analyzed. All patients underwent evaluation with FDG-PET/CT. Thyroid nodules were sonographically categorized by Thyroid Image Reporting and Data System (TIRADS) criteria. FDG uptake in the thyroid nodules was visually compared to the remainder of the thyroid tissue and categorized as pathological or non-pathological. In cases of pathologically increased uptake, maximum standardized uptake values (SUVmax) of the suspicious nodule and the perinodular thyroid tissue were determined. Depending on the results of the FDG-PET/CT, patients underwent thyroid surgery (pathological FDG uptake) or follow-up examinations (non-pathological FDG uptake). The endpoints for comparison with the FDG uptake were either histological results or sonographic follow-up examinations of at least five years. RESULTS: In 18/65 (28%) patients, PET/CT showed visually pathological FDG uptake in the suspicious thyroid nodules (SUVmax 7.1 ± 4.6). Of these nodules, 3/18 (17%) were sonographically categorized as TIRADS 4a, 11/18 (61%) nodules as TIRADS 4b, 3/18 (17%) nodules as TIRADS 4c, and 1/18 (6%) nodule as TIRADS 5. The other nodules without pathological FDG uptake were categorized as TIRADS 4a in 24/47 (51%) patients, as TIRADS 4b in 18/47 (38%), and as TIRADS 4c in 5/47 (11%) patients. Twenty-three patients (18 FDG positive, 5 FDG negative) underwent surgery. The other patients underwent follow-up examinations with stability on observation over at least five years as a surrogate endpoint. Taking into consideration that FDG-PET/CT was rated as true negative in 42/47 patients with stability on sonographic follow-up, sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET/CT in detecting malignancy in the suspicious thyroid nodules were 100%, 87%, 61%, and 100%, respectively. CONCLUSION: FDG-PET/CT allows stratification of patients with sonographically suspicious and scintigraphically hypofunctional thyroid nodules with a positive predictive value of 61% and negative predictive value of 100%. The absence of visually pathological FDG uptake in suspicious thyroid nodules may be useful for avoiding unnecessary thyroid surgery.

Aborted sudden cardiac death and a mother with suspected metabolic myopathy.

Aborted sudden cardiac death (SCD) has not been reported as initial manifestation of cardiac involvement in metabolic myopathy (MM). A 20-year-old female with a previous history of three syncopes, hyperhidrosis, and recurrent tick bites experienced aborted SCD. Her mother presented with MM, and a history of pituitary adenoma, nephroptosis, arterial hypertension, depression, migraine, goiter, pancreatitis, osteoporosis, hyperhidrosis, multiple muscle ruptures, and hyperlipidemia. After a few days of disorientation and amnesia, the young female recovered completely. Clinical neurological examination was noticeable for partial ophthalmoparesis and mild hyperprolactinemia. She received an implantable cardioverter defibrillator, which did not discharge so far. Recurrent syncopes and aborted SCD may be the initial manifestation of MM with multiple organ involvement. The family history is important in cases with aborted SCD to guide the diagnostic work-up. Phenotypic heterogeneity between the family members may be an indicator of MM.

Implantable loop-recorders in myopathic and non-myopathic patients with left ventricular hypertrabeculation/noncompaction.

BACKGROUND: Left ventricular noncompaction is associated with arrhythmias. The indication for implantation of devices for primary prophylaxis of sudden cardiac death in noncompaction is controversial, especially for patients without severe systolic dysfunction. The use of implantable loop-recorders to detect arrhythmias has not been reported so far. METHODS: A retrospective analysis of indications and results of implantation of loop-recorders in patients with left ventricular noncompaction. RESULTS: Loop-recorders were implanted in 3 patients with noncompaction and moderately or preserved left ventricular systolic function. The recorders revealed pauses N3 s, leading to pacemaker implantation in one patient, and tachycardia leading to radiofrequency ablation in another patient. In the third patient, no arrhythmias have so far been detected. CONCLUSION: From our limited experience we consider monitoring by a loop-recorder as a useful tool to detect arrhythmias in noncompaction-patients.

Arrhythmia-related workup in hereditary myopathies.

BACKGROUND: Arrhythmias determine life expectancy in patients with hereditary myopathies. AIMS: The aim of this study was to summarize recent advances in the diagnosis and management of arrhythmias in hereditary myopathies. METHODS: Literature search via PubMed and inclusion of own experiences were performed. RESULTS: All types of arrhythmias can be found in patients with hereditary myopathies, but some are more prevalent than others. Arrhythmias reported in myopathies include atrial fibrillation, atrial flutter, sick-sinus syndrome, preexcitation syndromes, atrioventricular conduction delay, intraventricular conduction delay, and ventricular tachycardia. Sudden cardiac death is a common finding in certain myopathies, and patients at risk for ventricular arrhythmias and sudden cardiac death should be identified early enough to implant a cardioverter-defibrillator to prevent a fatal outcome. Myopathies associated with a high risk for arrhythmias include laminopathies, Emery-Dreifuss muscular dystrophy, myotonic dystrophy I, mitochondrial myopathies, fatty-acid oxidation defects, and dystrophinopathies. To detect arrhythmias with high risk for sudden cardiac death, patients require close follow-up investigations or an implantable loop recorder. Documentation of severe arrhythmias requires immediate treatment according to established guidelines. CONCLUSIONS: Patients with certain hereditary myopathies carry an increased risk for developing severe supraventricular or ventricular arrhythmias and for dying of sudden cardiac death. Close follow-up and long-term surveillance of the electrocardiogram may prevent fatal complications of arrhythmias in these patients.

Novel c.367_369del LMNA mutation manifesting as severe arrhythmias, dilated cardiomyopathy, and myopathy.

OBJECTIVE: The 3-bp deletion in exon 2 of the Lamin A/C (LMNA) gene has not been described in association with dilated cardiomyopathy, which is characterized by progressive heart failure, atrioventricular (AV) block, tachyarrhythmias, and variable skeletal muscle involvement. CASE REPORT: In a 43-year-old woman with a long-term history of palpitations and newly diagnosed AV blocks I and II, ventricular ectopic beats, inducible nonsustained ventricular tachycardias (VTs), cardiac arrest, and successful resuscitation, an implantable cardioverter defibrillator was successfully implanted. Her family history was positive for sudden cardiac death (her father and sister), dyspnea and heart failure (her grandmother and sister), palpitations (her brother), and elevated levels of creatine-kinase (CK) (her sister). Two cousins had died of nonspecific muscular dystrophy at ages 10 years and 11 years. Upon neurological investigations revealing sore neck muscles, reduced tendon reflexes, and detached, spot-like white matter lesions bilaterally, a neuromuscular disorder was suspected. The direct sequencing of all exons and flanking intronic regions of the LMNA gene detected the heterozygote 3-bp deletion (AAG) c.367_369del in exon 2 of the gene. This mutation resulted in the deletion of a lysine at position 123 (p.lys123del) in the lamin A/C protein. CONCLUSIONS: The novel 3-bp deletion in exon 2 of the LMNA gene may phenotypically manifest as dilated cardiomyopathy, heart failure, severe tachyarrhythmias, and muscular dystrophy. Sudden cardiac death from ventricular fibrillation may be prevented in LMNA mutation carriers if the diagnosis is established early enough to implant a cardioverter defibrillator.

Diagnostic yield of ink-jet prints from digital radiographs for the assessment of approximal carious lesions: ROC-analysis.

AIMS: To investigate the diagnostic quality of different quality, individually calibrated ink-jet printers for the very challenging dental radiographic task of approximal carious lesion detection. MATERIALS AND METHODS: A test-pattern evaluating resolution, contrast and homogeneity of the ink-jet prints was developed. 50 standardized dental radiographs each showing two neighbouring teeth in natural contact were printed on glossy paper with calibrated, randomly selected ink-jet printers (Canon S520 and iP4500, Epson Stylus Photo R2400). Printing size equalled the viewing size on a 17″ cathode-ray-tube monitor daily quality-tested according to German regulations. The true caries status was determined from serial sectioning and microscopic evaluation. 16 experienced observers evaluated the radiographs on a five-point confidence scale on all prints plus the viewing monitor with respect to the visibility of a carious lesion. A non-parametric Receiver-Operating Characteristics (ROC-) analysis was performed explicitly designed for the evaluation of readings stemming from identical samples but different modality. Significant differences are expressed by a critical ratio z exceeding ±2. Diagnostic accuracy was determined by the area (Az) underneath the ROC-curves. RESULTS: Average Az-values ranged between 0.62 (S520 and R2400) and 0.64 (monitor, iP4500), with no significant difference between modalities (P=0.172). Neither significant (range mean z: -0.40 (S520) and -0.11 (iP4500)) nor clinically relevant differences were found between printers and viewing monitor. CONCLUSIONS: Our results for a challenging task in dental radiography indicate that calibrated, off-the-shelf ink-jet printers are able to reproduce (dental) radiographs at quality levels sufficient for radiographic diagnosis in a typical dental working environment.

Seizure as initial manifestation of aortic dissection type a.

BACKGROUND: Seizure as the initial manifestation of aortic dissection is rare. CASE REPORT: An 88-year-old female experienced a first generalized tonic clonic seizure, which was terminated with midazolam. Acute cerebral magnetic resonance imaging and angiography were non-informative. After awaking she complained about cramping pain in the right upper extremity, which was accompanied by involuntary flexion movements of the right upper extremity. Blood pressure was initially normal. Blood gases revealed metabolic acidosis and blood chemical investigations a markedly increased D-dimer. Consecutively blood pressure declined and transthoracic echocardiography showed pericardial effusion. A computed tomography scan of the thorax revealed an aortic dissection type A. The patient died 16 hours after admission after cardiothoracic surgeons had refused surgical treatment. CONCLUSION: This case shows that a generalized tonic-clonic seizure may be the initial manifestation of an aortic dissection type A in the absence of thoracic chest pain and that brachyalgia may not develop earlier than with progression of the dissection.

Deficiency of mannose-binding lectin, myopathy, calcified endomyocardial fibrosis, and left ventricular noncompaction.

In a patient with mannose-binding lectin deficiency and metabolic myopathy with recurrent respiratory infections, left ventricular hypertrabeculation/noncompaction was diagnosed by echocardiography and confirmed at autopsy. In contrast with previously described cases, extensive endocardial calcifications were found, possibly as a result of recurrent endomyocarditis during the recurrent infections.

Quality of individually calibrated customary printers for assessment of typical dental diagnoses on glossy paper prints: a multicenter pilot study.

OBJECTIVE: The objective of this study was to compare dental radiographs printed on glossy paper from calibrated low-cost printers with monitor display. STUDY DESIGN: Three typical intraoral radiographs were selected and a questionnaire was developed with questions assessing accuracy and subjective quality. A test pattern was designed for printer calibration. After calibration, radiographs were printed on glossy paper with 3 ink-jet and 2 thermo-sublimation printers. Sixteen raters evaluated the printed radiographs, 9 of them also on standardized viewing monitors. Subjective ratings were compared, and an ROC-analysis based on expert-consensus monitor readings was performed. RESULTS: Low inter-rater reproducibility (mean Cohen's Kappa monitor: 0.49; printers: 0.44), but high diagnostic accuracy was found for all printers (areas [Az] underneath the ROC curves: 0.725 to 0.884). The overlap between the 95% Az confidence intervals of the mean indicate no significant differences. CONCLUSION: Our preliminary findings indicate that dental radiographs may be evaluated on glossy paper prints of calibrated customary printers.

Left ventricular hypertrabeculation (noncompaction) with prominent calcifications in a patient with mannose-binding lectin deficiency and unclassified myopathy.

OBJECTIVES: The aim of this study was to report the histological findings of a patient with left ventricular hypertrabeculation (LVHT, noncompaction), mannose-binding lectin (MBL) deficiency, and unclassified myopathy in whom also endocardial thickening and calcifications over the compacted and noncompacted layer were found. CASE REPORT: In a 47-year-old man with left bundle-branch block, ventricular runs, and dilative cardiomyopathy with systolic dysfunction since childhood, LVHT was detected at 40 years of age. At the same time, intracardial calcifications were recognized on a thoracic computed tomographic scan. MBL deficiency was identified as the cause of recurrent respiratory infections since childhood at 45 years of age. Easy fatigability, myalgias, ptosis, and warming-up phenomenon were attributed to an unclassified myopathy at 44 years of age. After death from a sepsis with Staphylococcus aureus, autopsy confirmed LVHT and additionally revealed endocardial thickening, endocardial fibrosis, foci of calcifications within the endocardium, and accumulations of degenerated cardiomyocytes within the calcifications. Endocardial fibrosis and calcifications were located over the compacted as well as noncompacted segments. They were attributed to LVHT rather than the MBL deficiency-triggered infections or the preterminal sepsis. CONCLUSIONS: LVHT may be associated with MBL deficiency, unclassified myopathy, and endocardial fibrosis with calcifications over the compacted and noncompacted layer. Endocardial fibrosis with prominent calcifications seems to be a rare manifestation of LVHT.

Disappearance of left ventricular hypertrabeculation/noncompaction after biventricular pacing in a patient with polyneuropathy.

BACKGROUND: Disappearance of left ventricular hypertrabeculation/noncompaction (LVHT) has been reported only in myocarditis. We report disappearance of LVHT after implantation of a biventricular pacemaker in a 68-year-old female. She suffered from symmetrical polyneuropathy and heart failure New York Heart Association Class IV due to dilated cardiomyopathy despite angiotensin-converting enzyme inhibitors, beta-blockers, digitalis, and diuretics. Echocardiographically, she showed an enlarged poorly contracting left ventricle with LVHT involving the lateral and apical wall. METHODS AND RESULTS: In January 2001, a biventricular pacemaker system was implanted. From that time, her condition and left ventricular systolic function improved and the left ventricular size decreased. Surprisingly, LVHT could no longer be detected echocardiographically. CONCLUSIONS: We explain LVHT disappearance as follows: (1) the trabeculations are still existing, but not visible any more because of the better contraction state of the left ventricle; (2) the trabeculations have regressed because they are not needed anymore; and (3) the trabeculations have been falsely diagnosed and were in fact ventricular thrombi, which is quite unlikely because no embolic events occurred. LVHT can disappear if dilatation of the cardiac cavities and severely reduced systolic function regress. The dynamics of LVHT may represent an adaption mechanism of the cardiac function to compensate for a temporary failing myocardium.

Pressure-induced internal redox reaction of Cs2[PdI4].I2, Cs2[PdBr4].I2, and Cs2[PdCl4].I2.

The pressure-induced redox reaction within the system Cs2[Pd2+I4].I2/Cs2[Pd4+I6] was investigated by means of powder X-ray diffraction. Analogous high-pressure X-ray diffraction experiments were performed on the isostructural compounds Cs2[PdX4].I2 (X = Cl, Br). Additionally, the phase transition of Cs2[PdBr4].I2 to Cs2[PdBr4I2] was characterized by means of Raman scattering experiments as well as theoretical calculations based on density functional theory. On the basis of experimentally determined crystal structure data, a pathway for the topology of the redox reactions was developed and outlined.

Fluorescent T7 display phages obtained by translational frameshift.

Lytic phages form a powerful platform for the display of large cDNA libraries and offer the possibility to screen for interactions with almost any substrate. To visualize these interactions directly by fluorescence microscopy, we constructed fluorescent T7 phages by exploiting the flexibility of phages to incorporate modified versions of its capsid protein. By applying translational frameshift sequences, helper plasmids were constructed that expressed a fixed ratio of both wild-type capsid protein (gp10) and capsid protein fused to enhanced yellow fluorescent protein (EYFP). The frameshift sequences were inserted between the 3' end of the capsid gene and the sequence encoding EYFP. Fluorescent fusion proteins are only formed when the ribosome makes a -1 shift in reading frame during translation. Using standard fluorescence microscopy, we could sensitively monitor the enrichment of specific binders in a cDNA library displayed on fluorescent T7 phages. The perspectives of fluorescent display phages in the fast emerging field of single molecule detection and sorting technologies are discussed.