Arch-first technique via clamshell incision: successful surgical reoperation for aortic arch dissection

We report a case of successful reoperation for aortic arch dissection with use of the "arch-first" technique in a patient who had Marfan syndrome. Extracorporeal circulation was initiated via right subclavian artery cannulation, and the chest was entered through a clamshell incision for the best exposure. When the patient was cooled to 18 degrees C, the perfusion was stopped. After the 1st aortic arch anastomosis to a 30-mm Dacron graft, cerebral perfusion was reestablished via the right subclavian artery. The aortic repair was then completed. The cerebral ischemic time was 18 minutes, the aortic cross-clamp time was 69 minutes, and the total extracorporeal circulation time was 334 minutes. The patient was discharged from the hospital on postoperative day 10 with no neurologic impairment. The arch-first technique shortens the duration of brain ischemia. When combined with a clamshell incision, the technique is particularly helpful for reoperation of the aortic arch and thoracic aorta.     

The rare coexistence of high titer inhibitor development and gastrointestinal stromal tumor in a patient with severe hemophilia: A case report

Hemophilia is a hereditary disease with impaired blood coagulation due to a genetic deficiency of blood coagulation factors. The development of inhibitors further complicates the course of the disease and management. The case is here reported of a haemophilia patient who presented with coexisting development of high titer inhibitor with Gastrointestinal Stromal Tumor (GIST) diagnosis and was admitted with upper gastrointestinal system bleeding. The patient had no prior history of inhibitor presence. During all procedures including surgery, excellent hemostasis was achieved with rFVIIa treatment and no hemorrhagic complication was observed. To the best of our knowledge, this constitutes the first reported case of GIST associated with inhibitor development in a hemophilia A patient.     

Predictive value of SYNTAX score II for clinical outcomes in cardiogenic shock underwent primary percutaneous coronary intervention; a pilot study

SYNTAX Score II (SSII) connects clinical variables with coronary anatomy. We investigated the prognostic value of SSII in patients with ST segment elevated myocardial infarction (STEMI) complicated with cardiogenic shock treated with primary percutaneous coronary intervention (PPCI). In this retrospective analysis, we evaluated the in-hospital prognostic impact of SSII on 492 patients with STEMI complicated with cardiogenic shock treated with PPCI. Patients were stratified by tertiles of SSII, in-hospital clinical outcomes were compared between those groups. In-hospital univariate analysis revealed higher rates of in-hospital death for patients with SSII in tertile 3, as compared to patients with SSII in tertile 1 (OR 17.4, 95% CI 10.0–30.2, p?<?0.001). After adjustment for confounding baseline variables, SSII in tertile 3 was associated with 6.2-fold hazard of in-hospital death (OR 6.2, 95% CI 2.6–14.1, p?<?0.001). SSII in patients with STEMI complicated with cardiogenic shock treated with PPCI provide an independent prognostic marker of in-hospital outcomes. Our data suggests SSII to be a simple, feasible and clinically applicable tool for rapid risk stratification in patients with STEMI complicated with cardiogenic shock treated with PPCI.     

The pleuro-esophageal muscle: a disregarded anatomical structure

A transverse muscular band extending from the left pleura to the esophagus was detected during routine dissection of posterior mediastinum in Anatomy Department of Ege University Medical Faculty. As a result of a detailed review of the literature, we found that this structure is named as the pleuro-esophageal muscle. This muscle was made of smooth fibers, acting as an anchoring structure to the lower part of the esophagus. While the entire esophageal muscle is smooth in the early stage of fetal development, this muscle probably derives as an early separation from the esophagus.     

Treatment Outcomes of Long-Pulsed Nd: YAG Laser for Two Different Subtypes of Rosacea

Background: A variety of lasers have been used for the treatment of rosacea. However, treatment of this condition with long-pulsed neodymium-doped yttrium aluminium garnet laser has not been reported yet. Objective: To assess the efficacy and safety of long-pulsed neodymium-doped yttrium aluminium garnet laser in two different subtypes (erythematotelangiectatic and papulopustular) of rosacea. Methods: A total of 66 patients were enrolled in the study. All of the patients were treated with long-pulsed neodymium-doped yttrium aluminium garnet laser with 3- to 4-week intervals. Rosacea severity score was assessed by using photographs. Improvement in severity was defined as the percentage reduction in severity scores from baseline to the end of treatment. Patients were also asked about their own opinions of improvement at the end of the treatment. Side effects were also documented. Results: Good to excellent improvement was achieved in up to 50 percent of the patients in the erythematotelangiectatic and papulopustular groups. Percent improvement of global severity was significantly greater in the erythematotelangiectatic patients than in the papulopustular patients. The majority of patients from both groups noted a significant improvement of the lesions. Hypopigmented atrophic scars were seen in two patients. Conclusion: The long-pulsed neodymium-doped yttrium aluminium garnet laser is a safe and effective treatment for vascular and inflammatory lesions of rosacea.Rosacea is a chronic inflammatory cutaneous disorder with periods of exacerbations and remissions. Clinical findings are characterized by flushing, erythema, telangiectasia, papules, and pustules. There are four recognized subtypes—erythematotelangiectatic (ETR), papulopustular (PPR), phymatous, and ocular.1 Although angiogenic and sebaceous factors have been implicated in the etiopathology of the disease, it remains unclear. Vascular abnormalities, dermal matrix degeneration, environmental factors, and microorganisms may have a potential role in the development of rosacea.2Rosacea may significantly affect patients’ lives, leading to considerable psychological and social distress over appearance. Therefore, management of this condition is very important. There is no definite cure. Electrosurgery and lasers can be used to decrease vascular lesions.3 Topical and/or oral antibiotics can be used to suppress the inflammatory lesions. Although these methods are moderately successful in controlling symptoms, relapse usually occurs shortly after the cessation of therapy.4,5Many types of lasers and light devices have been increasingly used in the treatment of rosacea. However, the role of long-pulsed neodymium-doped yttrium aluminium garnet (Nd:YAG) laser in this condition has not been well-studied. In this study, the authors assessed the efficacy of long-pulsed Nd:YAG laser in treating patients with two different subtypes (ETR and PPR patients) of rosacea.     

Sex work, drug use, HIV infection, and spread of sexually transmitted infections in Moscow, Russian Federation

Rates of HIV-1 infection are growing rapidly, and the epidemic of sexually transmitted infections is continuing at an alarming rate, in the Russian Federation. We did a cross-sectional study of sexually transmitted infections, HIV infection, and drug use in street youth at a juvenile detention facility, adults at homeless detention centres, and women and men at a remand centre in Moscow. 160 (79%) women at the remand centre were sex workers. 91 (51%) homeless women had syphilis. At least one bacterial sexually transmitted infection was present in 97 (58%) female juvenile detainees, 120 (64%) women at the remand centre, and 133 (75%) homeless women. HIV seroprevalence was high in women at the remand centre (n=7 [4%]), adolescent male detainees (5 [3%]), and homeless women (4 [2%]). In view of the interaction between sexually transmitted infections and HIV infection, these findings of high prevalence of sexually transmitted infections show that these disenfranchised populations have the potential to make a disproportionately high contribution to the explosive growth of the HIV epidemic unless interventions targeting these groups are implemented in the Russian Federation.     

Fear Assessment in Inflammatory Rheumatic diseases (FAIR) questionnaire: a cross-cultural adaptation and validation to the Turkish language

In chronic inflammatory rheumatic diseases (CIRD), it is important to understand patients’ fears towards their disease in order to improve patient-physician dialog, to raise the quality of care offered, and to optimize treatment adherence. In this study, we aimed to translate the Fear Assessment in Inflammatory Rheumatic diseases (FAIR) questionnaire into Turkish and evaluate its psychometric properties in patients with CIRD. One hundred fifteen patients filled the provided socio-demographic information form, FAIR-Tr questionnaire, Hospital Anxiety and Depression Scale (HADS), and Beck’s Hopelessness Scale (BHS). For the analysis of short-term reliability, 50 patients re-filled the FAIR-Tr questionnaire 1 week later. Internal consistency was evaluated with Cronbach’s α coefficient and test-retest reliability was evaluated with intraclass correlation coefficients (ICC). Construct validity analysis was investigated based on the correlation with HADS and BHS. All patients found FAIR-Tr easily understandable and acceptable. FAIR-Tr internal consistency (Cronbach’s α?=?0.93) and test-retest reliability (ICC?=?0.91) were excellent. Psychometric validation was proved upon observing high correlation with HADS (Anxiety, r?=?0.77; Depression, r?=?0.70) and moderate correlation with BHS (r?=?0.65). FAIR-Tr is a questionnaire that has excellent internal consistency and test-retest reliability. The successful correlation with HADS and BHS supported its psychometric validity in terms of evaluating the fear in CIRD cases. We think that FAIR-Tr is a specific scale that can help to evaluate the disease- and treatment-related fears of the Turkish patients with CIRD and may be useful in both routine practice and clinical studies.     

Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited

Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxel-averaged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.The creation of a comprehensive map of the connectional neuroanatomy of the human brain would be a fundamental achievement in neuroscience. However, despite the numerous efforts to date (for a historical review, see ref. 1), creating this map remains a challenge. A major limitation is that the current gold-standard technique for mapping structural connections, which requires the injection of axonal tracers, cannot be used in humans. The introduction of diffusion-weighted MRI (DWI) (2–4) and the subsequent advent of diffusion tensor MRI (DTI) (5) opened the possibility of exploring the structural properties of white matter in the living human brain (6). Local DWI measures are used clinically for the early detection of stroke and for the characterization of neurological disorders such as multiple sclerosis, epilepsy, and brain gliomas, among others (7). In addition, tractography approaches (8–12) that can infer structural brain connectivity based on brain-wide local DWI measurement have been developed (for reviews, see refs. 13 and 14). The success of DWI tractography as a method for studying fiber trajectories has led to a systematic characterization of large white-matter pathways of the living human brain (e.g., ref. 15), and now it is used routinely to provide a structural explanation for aspects of human brain function (16).A major limitation of DWI tractography is that its characterization of axonal pathways is based on indirect information and numerous assumptions. Local white matter orientation profiles are based on the statistical displacement profile (i.e., diffusion propagator) of water molecules in brain tissue on the coarse scale of a voxel, and fiber trajectories are inferred based on the adjacency of similar diffusion profiles. This approach differs fundamentally from conventional tract-tracing approaches in animals, which involve the physical transport of traceable molecules through the cells’ axoplasm over a large distance. Because these molecules occupy positions within the axon, it sometimes is possible to reconstruct the trajectory of individual neurons through the white matter (e.g., ref. 17). Given the inherent coarseness of DWI tractography, it can be argued that the prospect of using this method to reconstruct complex axonal pathways accurately in the human brain, in a manner similar to that used for molecular tracers in animals, is likely to be intrinsically problematic. Indeed, the limitations of DWI tractography techniques have been noted since their inception (8), and the anatomical accuracy of results from tractography based on the tensor model has been shown to be mixed (18). This inaccuracy has been attributed to two main factors. The first relates to the assumptions underlying tractography algorithms. For example, it has long been recognized that a simple tensor model (19) of local diffusion leads to problems in certain white matter regions where fibers cross within individual voxels. As a remedy, high angular resolution diffusion imaging (HARDI) methods (e.g., refs. 20–24) have been developed to enable better characterization of the diffusion displacement profile and to improve the accuracy of tractography. The second factor limiting accuracy stems from the low quality of clinical DWI data because of various sources of noise. Eddy current distortions, subject motion, physiological noise (see ref. 25 for a review), and susceptibility artifacts from echo planar imaging (EPI) (26) all lead to poor local characterization of diffusion and, consequently, to incorrect tractography results. Continuing advances in sequence design, MRI gradient hardware, and postprocessing correction schemes have overcome many of the initial problems (27) and have led to the belief that further acquisition improvements will result in more precise mapping of structural connections in the human brain (28). In fact, the assumption underlying many recent initiatives to map structural brain connectivity from DWI data is that improved image data quality and sophisticated diffusion modeling approaches will result in anatomically accurate maps of white matter connections (29). The goal of the present study is to investigate the validity of this assumption.To achieve this goal, we acquired high angular resolution DWI data from a normal adult rhesus macaque brain, ex vivo, at a spatial resolution of 250 microns (isotropic). This dataset is ideal for exploring the limits of DWI tractography because of its high signal-to-noise ratio (SNR) (for SNR computation, see SI Materials and Methods) and the almost complete absence of experimental confounds and artifacts such as those originating from patient motion, noise, cardiac pulsation, and EPI distortion that are typically encountered in in vivo studies. Using the axonal tracer results from a well-known atlas (17) as reference, we measured the sensitivity (i.e., the ability to detect true connections) and specificity (i.e., the ability to avoid false connections) of several DWI tractography implementations representative of the current state of the art. This approach allowed us to investigate whether sophisticated diffusion modeling techniques, when applied to DWI data of exceptional quality, would yield accurate maps of axonal connections.     

Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease

Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.Essential tremor is one of the most frequent movement disorders in humans (1). It is characterized primarily by postural or kinetic tremor of the arms and hands, but head, legs, voice, and other regions of the body may also be affected (2). The worldwide prevalence is 0.9%, increasing to more than 4% in elderly populations (1). Familial essential tremor is genetically heterogeneous. Genetic linkage studies of multiply affected families revealed three genomic regions segregating with the condition, on chromosomes 3q13 [ETM1; Online Mendelian Inheritance in Man (OMIM) 190300], 2p22-24 (ETM2; OMIM 602134), and 6p23 (ETM3; OMIM 611456) (3–5). No clearly causal mutations have been identified in these regions, although the common variant DRD3 p.S9G in the ETM1 region has been proposed as a risk factor and HS1BP3 p.A265G in the ETM2 region appeared in two multiply affected families (6, 7). Genomewide association studies of essential tremor reported associations with common variants in an intron of LINGO1 and in an intron of SLC1A2 (8–10). Recently, DNAJC13 p.N855S, which had been identified in Parkinson disease patients, was also found in two unrelated patients with essential tremor (11). Nonsense mutation p.Q290X in the RNA-binding protein FUS was identified by whole exome sequencing in a large family with essential tremor (ETM4; OMIM 614782) (12). Screening other subjects with essential tremor for FUS revealed two rare missense variants, suggesting that mutations in FUS explain a subset of cases with the condition (13, 14).In this study, we examined a six-generation family segregating essential tremor, and in multiple relatives, essential tremor as a feature of Parkinson disease. We carried out whole exome sequencing of genomic DNA from three severely affected family members and subsequent pedigree analysis to identify the genetic basis of essential tremor and Parkinson disease in the family.