Feasibility of post mortem cardiac proton density weighted fast field echo imaging in two cases of sudden death

OBJECTIVE The aim of this work is to investigate and compare cardiac proton density (PD) weighted fast field echo (FFE) post-mortem magnetic resonance (PMMR) imaging with standard cardiac PMMR imaging (T1-weighted and T2-weighted turbo spin-echo (TSE)), postmortem CT (PMCT) as well as autopsy. MATERIALS AND METHODS Two human cadavers sequentially underwent cardiac PMCT and PMMR imaging (PD-weighted FFE, T1-weighted and T2-weighted TSE) and autopsy. The cardiac PMMR images were compared to each other as well as to PMCT and autopsy findings. RESULTS For the first case, cardiac PMMR exhibited a focal region of low signal in PD-weighted FFE and T2-weighted TSE images, surrounded by a signal intense rim in the T2-weighted images. T1-weighted TSE and PMCT did not appear to identify any focal abnormality. Macroscopic inspection identified a blood clot; histology confirmed this to be a thrombus with an adhering myocardial infarction. In the second case, a myocardial rupture with heart tamponade was identified in all PMMR images, located at the anterior wall of the left ventricle; PMCT excluded additional ruptures. In PD-weighted FFE and T2-weighted TSE images, it occurred hypo-intense, while resulting in small clustered hyper-intense spots in T1-weighted TSE. Autopsy confirmed the PMMR and PMCT findings. CONCLUSIONS Presented initial results have shown PD-weighted FFE to be a valuable imaging sequence in addition to traditional T2-weighted TSE imaging for blood clots and myocardial haemorrhage with clearer contrast between affected and healthy myocardium.

The Application of Comorbidity Indices to Predict Early Postoperative Outcomes After Laparoscopic Roux-en-Y Gastric Bypass: A Nationwide Comparative Analysis of Over 70,000 Cases

BACKGROUND: Patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) often have substantial comorbidities, which must be taken into account to appropriately assess expected postoperative outcomes. The Charlson/Deyo and Elixhauser indices are widely used comorbidity measures, both of which also have revised algorithms based on enhanced ICD-9-CM coding. It is currently unclear which of the existing comorbidity measures best predicts early postoperative outcomes following LRYGB. METHODS: Using the Nationwide Inpatient Sample, patients 18 years or older undergoing LRYGB for obesity between 2001 and 2008 were identified. Comorbidities were assessed according to the original and enhanced Charlson/Deyo and Elixhauser indices. Using multivariate logistic regression, the following early postoperative outcomes were assessed: overall postoperative complications, length of hospital stay, and conversion to open surgery. Model performance for the four comorbidity indices was assessed and compared using C-statistics and the Akaike's information criterion (AIC). RESULTS: A total of 70,287 patients were included. Mean age was 43.1 years (SD, 10.8), 81.6 % were female and 60.3 % were White. Both the original and enhanced Elixhauser indices modestly outperformed the Charlson/Deyo in predicting the surgical outcomes. All four models had similar C-statistics, but the original Elixhauser index was associated with the smallest AIC for all of the surgical outcomes. CONCLUSIONS: The original Elixhauser index is the best predictor of early postoperative outcomes in our cohort of patients undergoing LRYGB. However, differences between the Charlson/Deyo and Elixhauser indices are modest, and each of these indices provides clinically relevant insight for predicting early postoperative outcomes in this high-risk patient population.

The treatment and outcome of peri-prosthetic infection of the ankle: a single cohort-centre experience of 34 cases

The treatment of peri-prosthetic joint infection (PJI) of the ankle is not standardised. It is not clear whether an algorithm developed for hip and knee PJI can be used in the management of PJI of the ankle. We evaluated the outcome, at two or more years post-operatively, in 34 patients with PJI of the ankle, identified from a cohort of 511 patients who had undergone total ankle replacement. Their median age was 62.1 years (53.3 to 68.2), and 20 patients were women. Infection was exogenous in 28 (82.4%) and haematogenous in six (17.6%); 19 (55.9%) were acute infections and 15 (44.1%) chronic. Staphylococci were the cause of 24 infections (70.6%). Surgery with retention of one or both components was undertaken in 21 patients (61.8%), both components were replaced in ten (29.4%), and arthrodesis was undertaken in three (8.8%). An infection-free outcome with satisfactory function of the ankle was obtained in 23 patients (67.6%). The best rate of cure followed the exchange of both components (9/10, 90%). In the 21 patients in whom one or both components were retained, four had a relapse of the same infecting organism and three had an infection with another organism. Hence the rate of cure was 66.7% (14 of 21). In these 21 patients, we compared the treatment given to an algorithm developed for the treatment of PJI of the knee and hip. In 17 (80.9%) patients, treatment was not according to the algorithm. Most (11 of 17) had only one criterion against retention of one or both components. In all, ten of 11 patients with severe soft-tissue compromise as a single criterion had a relapse-free survival. We propose that the treatment concept for PJI of the ankle requires adaptation of the grading of quality of the soft tissues. Cite this article: Bone Joint J 2014;96-B:772-7.

Accuracy of the withdrawal reflex for localization of the site of cervical disk herniation in dogs: 35 cases (2004-2007)

OBJECTIVE To evaluate the accuracy of neurologic examination versus magnetic resonance imaging (MRI) in localization of cervical disk herniation and evaluate the usefulness of withdrawal reflex testing in dogs. DESIGN Retrospective case series. ANIMALS 35 client-owned dogs with a single-level cervical disk herniation as determined via MRI. PROCEDURES 1 of 2 board-certified neurologists performed a complete neurologic examination in each dog. Clinical signs of a cervical lesion included evidence of neck pain and tetraparesis. The withdrawal reflex was used for neuroanatomic localization (C1-C5 or C6-T2). Agreement between results of neurologic and MRI examinations was determined. RESULTS Agreement between neurologic and MRI diagnoses was 65.8%. In 11 dogs in which the lesion was clinically localized to the C6-T2 segment on the basis of a decreased withdrawal reflex in the forelimbs, MRI revealed an isolated C1-C5 disk lesion. In 1 dog, in which the lesion was suspected to be at the C1-C5 level, MRI revealed a C6-T2 lesion. Cranial cervical lesions were significantly associated with an incorrect neurologic diagnosis regarding site of the lesion. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the withdrawal reflex in dogs with cervical disk herniation is not reliable for determining the affected site and that a decreased withdrawal reflex does not always indicate a lesion from C6 to T2.

Vulnerability to Heatwaves, Floods and Mass Movements in Mountainous Terrain: Test Cases in South Tyrol

South Tyrol is a region that has been often affected by various mountain hazards such as floods, flash floods, debris flows, rock falls, and snow avalanches. Furthermore, areas located in lower altitudes are often influenced by high temperatures and heat waves. Climate change is expected to influence the frequency, magnitude, and spatial extent of these natural phenomena. For this reason, local authorities and other stakeholders are in need of tools that can enable them to reduce the risk posed by these processes. In the present study, a variety of methods are applied at local level in different places in South Tyrol that aim at: (1) the assessment of future losses caused by the occurrence of debris flows by using a vulnerability curve, (2) the assessment of social vulnerability based on the risk awareness of the exposed people to floods, and (3) the assessment of spatial exposure and social vulnerability of the exposed population to heat waves. The results show that, in South Tyrol, the risk to a number of hazards can be reduced by: (1) improving documentation for past events in order to improve existing vulnerability curves and the assessment of future losses, (2) raising citizens' awareness and responsibility to improve coping capacity to floods, and (3) extending heat wave early warning systems to more low-lying areas of South Tyrol.

Fatal contact shot to the chest caused by the gas jet from a muzzle-loading pistol discharging only black powder and no bullet: case study and experimental simulation of the wounding effect.

In modern medico-legal literature, only a small number of publications deal with fatal injuries from black powder guns. Most of them focus on the morphological features such as intense soot soiling, blast tattooing and burn effects in close-range shots or describe the wound ballistics of spherical lead bullets. Another kind of "unusual" and potentially lethal weapons are handguns destined for firing only blank cartridges such as starter and alarm pistols. The dangerousness of these guns is restricted to very close and contact range shots and results from the gas jet produced by the deflagration of the propellant. The present paper reports on a suicide committed with a muzzle-loading percussion pistol cal. 45. An unusually large stellate entrance wound was located in the precordial region, accompanied by an imprint mark from the ramrod and a faint greenish discoloration (apparently due to the formation of sulfhemoglobin). Autopsy revealed an oversized powder cavity, multiple fractures of the anterior thoracic wall as well as ruptures of the heart, the aorta, the left hepatic lobe and the diaphragm. In total, the zone of mechanical destruction had a diameter of approx. 15 cm. As there was no exit wound and no bullet lodged in the body, the injury was caused exclusively by the inrushing combustion gases of the propellant (black powder) comparable with the gas jet of a blank cartridge gun. In contact shots to ballistic gelatine using the suicide's pistol loaded with black powder but no projectile, the formation of a nearly spherical cavity could be demonstrated by means of a high-speed camera. The extent of the temporary cavity after firing with 5 g of black powder roughly corresponded to the zone of destruction found in the suicide's body.

Stability and relapse after orthodontic treatment of deep bite cases-a long-term follow-up study.

The purpose of this long-term follow-up study was twofold-firstly, to assess prevalence of relapse after treatment of deep bite malocclusion and secondly, to identify risk factors that predispose patients with deep bite malocclusion to relapse. Sixty-one former patients with overbite more than 50% incisor overlap before treatment were successfully recalled. Clinical data, morphometrical measurements on plaster casts before treatment, after treatment and at long-term follow-up, as well as cephalometric measurements before and after treatment were collected. The median follow-up period was 11.9 years. Patients were treated by various treatment modalities, and the majority of patients received at least a lower fixed retainer and an upper removable bite plate during retention. Relapse was defined as increase in incisor overlap from below 50% after treatment to equal or more than 50% incisor overlap at long-term follow-up. Ten per cent of the patients showed relapse to equal or larger than 50% incisor overlap, and their amount of overbite increase was low. Among all cases with deep bite at follow-up, gingival contact and palatal impingement were more prevalent in partially corrected noncompliant cases than in relapse cases. In this sample, prevalence and amount of relapse were too low to identify risk factors of relapse.

The modified coronally advanced tunnel combined with an enamel matrix derivative and subepithelial connective tissue graft for the treatment of isolated mandibular Miller Class I and II gingival recessions: a report of 16 cases.

OBJECTIVES To clinically evaluate the healing of mandibular Miller Class I and II isolated gingival recessions treated with the modified coronally advanced tunnel (MCAT) in conjunction with an enamel matrix derivative (EMD) and subepithelial connective tissue graft (SCTG). METHOD AND MATERIALS Sixteen healthy patients (13 women and 3 men) exhibiting one isolated mandibular Miller Class I and II gingival recessions of a depth of ≥ 3 mm, were consecutively treated with the MCAT in conjunction with EMD and SCTG. Treatment outcomes were assessed at baseline and at 12 months postoperatively. The primary outcome variable was complete root coverage (CRC) (eg, 100% root coverage). RESULTS Postoperative pain and discomfort were low and no complications such as postoperative bleeding, allergic reactions, abscesses, or loss of SCTG were observed. At 12 months, statistically significant (P < .0001) root coverage was obtained in all 16 defects. CRC was measured in 12 out of the 16 cases (75%) while in the remaining 4 defects root coverage amounted to 90% (in two cases) and 80% (in two cases), respectively. Mean root coverage was 96.25%. Mean keratinized tissue width increased from 1.98 ± 0.8 mm at baseline to 2.5 ± 0.9 mm (P < .0001) at 12 months, while mean probing depth did not show any statistically significant changes (ie, 1.9 ± 0.3 mm at baseline vs 1.8 ± 0.2 mm at 12 months). CONCLUSION Within their limits, the present results indicate that the described treatment approach may lead to predictable root coverage of isolated mandibular Miller Class I and II gingival recessions.

Cardiovascular changes after administration of aerosolized salbutamol in horses: five cases.

Prevention and treatment of intraoperative hypoxemia in horses is difficult and both efficacy and safety of therapeutic maneuvers have to be taken into account. Inhaled salbutamol has been suggested as treatment of hypoxia in horses during general anesthesia, due to safety and ease of the technique. The present report describes the occurrence of clinically relevant unwanted cardiovascular effects (i.e. tachycardia and blood pressure modifications) in 5 horses undergoing general anesthesia in dorsal recumbency after salbutamol inhalation. Balanced anesthesia based on inhalation of isoflurane in oxygen or oxygen and air and continuous rate infusion (CRI) of lidocaine, romifidine, or combination of lidocaine and guaifenesine and ketamine was provided. Supportive measures were necessary to restore normal cardiovascular function in all horses but no long-term adverse effects were noticed in any of the cases.

Genetic Engineering of Induced Pluripotent Stem Cells and Reprogramming to Motor Neurons to Elucidate Selective Motor Neuron Death in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, fatal within 1 to 5 years after onset of symptoms. About 3 out of 100’000 persons are diagnosed with ALS and there is still no cure available [1, 2]. 95% of all cases occur sporadically and the aetiology remains largely unknown [XXXX]. However, up to now 16 genes were identified to play a role in the development of familial ALS. One of these genes is FUS that encodes for the protein fused in sarcoma/translocated in liposarcoma (FUS/TLS). Mutations in this gene are responsible for some cases of sporadic as well as of inherited ALS [3]. FUS belongs to the family of heterogeneous nuclear ribonucleoproteins and is predicted to be involved in several cellular functions like transcription regulation [4], RNA splicing [5, 6], mRNA transport in neurons [7] and microRNA processing [8]. Aberrant accumulation of mutated FUS has been found in the cytoplasm of motor neurons from ALS patients [9]. The mislocalization of FUS is based on a mutation in the nuclear localization signal of FUS [10]. However, it is still unclear if the cytoplasmic localization of FUS leads to a toxic gain of cytoplasmic function and/or a loss of nuclear function that might be crucial in the course of ALS. The goal of this project is to characterize the impact of ALS-associated FUS mutations on in vitro differentiated motor neurons. To this end, we edit the genome of induced pluripotent stem cells (iPSC) using transcription activator-like effector nucleases (TALENs) [11,12] to create three isogenic cell lines, each carrying an ALS-associated FUS mutation (G156E, R244C and P525L). These iPSC’s will then be differentiated to motor neurons according to a recently establishe protocol (Ref Wichterle) and serve to study alterations in the transcriptome, proteome and metabolome upon the expression of ALS-associated FUS. With this approach, we hope to unravel the molecular mechanism leading to FUS-associated ALS and to provide new insight into the emerging connection between misregulation of RNA metabolism and neurodegeneration, a connection that is currently implied in a variety of additional neurological diseases, including spinocerebellar ataxia 2 (SCA-2), spinal muscular atrophy (SMA), fragile X syndrome, and myotonic dystrophy.

Oral syphilis: a series of 5 cases.

Syphilis is an infectious, usually sexually transmitted, disease caused by Treponema pallidum, subspecies pallidum. Because of the increasing prevalence in Europe during the past few years, dentists could be confronted with patients with oral manifestations of syphilis. Because oral lesions are highly contagious, it is vital to make the correct diagnosis quickly to initiate the proper therapy and to interrupt the chain of infection. We present the cases of 5 patients with syphilis-related oral lesions. These cases are representative because of their clinical presentation, age, and gender distribution and the diagnostic approach. The aim of the present report is to emphasize the importance of the dentist knowing and identifying syphilis in different stages to diagnose the disease and institute treatment at an early stage.

Genetic Engineering of Induced Pluripotent Stem Cells and Reprogramming to Motor Neurons to Elucidate Selective Motor Neuron Death in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, fatal within 1 to 5 years after onset of symptoms. About 3 out of 100’000 persons are diagnosed with ALS and there is still no cure available [1, 2]. 95% of all cases occur sporadically and the aetiology remains largely unknown [3]. However, up to now 16 genes were identified to play a role in the development of familial ALS. One of these genes is FUS that encodes for the protein fused in sarcoma (FUS). Mutations in this gene are responsible for some cases of sporadic as well as of inherited ALS [4]. FUS belongs to the family of heterogeneous nuclear ribonucleoproteins and is predicted to be involved in several cellular functions like transcription regulation, RNA splicing, mRNA transport in neurons and microRNA processing [5] Aberrant accumulation of mutated FUS has been found in the cytoplasm of motor neurons from ALS patients [6]. The mislocalization of FUS is based on a mutation in the nuclear localization signal of FUS [7]. However, it is still unclear if the cytoplasmic localization of FUS leads to a toxic gain of cytoplasmic function and/or a loss of nuclear function that might be crucial in the course of ALS. The goal of this project is to characterize the impact of ALS-associated FUS mutations on in vitro differentiated motor neurons. To this end, we edit the genome of induced pluripotent stem cells (iPSC) using transcription activator-like effector nucleases (TALENs) [8,9] to create three isogenic cell lines, each carrying an ALS-associated FUS mutation (G156E, R244C and P525L). These iPSC’s will then be differentiated to motor neurons according to a recently established protocol [10] and serve to study alterations in the transcriptome, proteome and metabolome upon the expression of ALS-associated FUS. With this approach, we hope to unravel the molecular mechanism leading to FUS-associated ALS and to provide new insight into the emerging connection between misregulation of RNA metabolism and neurodegeneration, a connection that is currently implied in a variety of additional neurological diseases, including spinocerebellar ataxia 2 (SCA-2), spinal muscular atrophy (SMA), fragile X syndrome, and myotonic dystrophy. [1] Cleveland, D.W. et al. (2001) Nat Rev Neurosci 2(11): 806-819 [2] Sathasivam, S. (2010) Singapore Med J 51(5): 367-372 [3] Schymick, J.C. et al. (2007) Hum Mol Genet Vol 16: 233-242 [4] Pratt, A.J. et al. (2012). Degener Neurol Neuromuscul Dis 2012(2): 1-14 [5] Lagier-Tourenne, C. Hum Mol Genet, 2010. 19(R1): p. R46-64 [6] Mochizuki, Y. et al. (2012) J Neurol Sci 323(1-2): 85-92 [7] Dormann, D. et al. (2010) EMBO J 29(16): 2841-2857 [8] Hockemeyer, D. et al. (2011) Nat Biotech 29(8): 731-734 [9] Joung, J.K. and J.D. Sander (2013) Nat Rev Mol Cell Biol 14(1): 49-55 [10]Amoroso, M.W. et al. (2013) J Neurosci 33(2): 574-586.