Fatal cardiac perforation and pulmonary embolism of leaked cement after percutaneous vertebroplasty

Percutaneous vertebroplasty consists of percutaneous injection of polymethylmethacrylate (PMMA) via a transpedicular approach for the treatment of collapsed osteoporotic or metastatic vertebrae. Even if percutaneous vertebroplasty is considered to be minimally invasive, threatening complications can occur. Cement leakage is the most common complication of percutaneous vertebroplasty. Rigorous patient selection and individual therapeutic strategy may reduce the occurrence of leakage, in particular the risk of cement entry into the venous system and the spinal canal is the potent major hazard of this technique. Cement pulmonary and cardiac embolism are reported in literature as a cause of unexpected death after percutaneous vertebroplasty. Authors report a fatal case of pulmonary cement embolization occurred after vertebroplasty with haemopericardium, due to the perforation of the right atrium wall from a cement solidified fragment. A complete post mortem examination documented the presence of multiple cement fragments in the pulmonary arteries and transmural perforation of the wall of the right atrium by a whitish needle-like foreign body. Pulmonary microembolization was observed under polarized ligh

Hospital autopsy for prevention of sudden cardiac death

In the past 20 years, cardiovascular mortality has decreased in highincome countries in response to the adoption of preventive measures to reduce the burden of coronary artery disease and heart failure. Despite these encouraging results, cardiovascular diseases are responsible for approximately 17 million deaths every year in the world, approximately 25% of which are sudden cardiac death. The risk of sudden cardiac death is higher in men than in women, and it increases with age due to the higher prevalence of coronary artery disease in older age. Accordingly, the sudden cardiac death rate is estimated to range from 1.40 per 100 000 person-years in women to 6.68 per 100 000 person-years in men. Sudden cardiac death in younger individuals has an estimated incidence of 0.46\u20133.7 events per 100 000 person-years, corresponding to a rough estimate of 1100\u20139000 deaths in Europe and 800\u20136200 deaths in the USA every year. Cardiac diseases associated with sudden cardiac death differ in young vs. older individuals. In the young there is a predominance of channelopathies and cardiomyopathies, myocarditis and substance abuse, while in older populations, chronic degenerative diseases predominate. In younger persons, the cause of sudden cardiac death may be elusive even after autopsy, because conditions such as inherited channelopathies or drug-induced arrhythmias that are devoid of structural abnormalities are epidemiologically relevant in this age group. Identification of the cause of an unexpected death provides the family with partial understanding and rationalization of the unexpected tragedy, which facilitates the coping process and allows an understanding of whether the risk of sudden death may extend to family members. Accordingly, author present their experience with autopsies of unexplained sudden death young victims in which a cardiac origin was suspected and the relevance of a standardized protocol for heart examination and histological sampling, as well as for toxicology and molecular investigation

Impairment of lysosomal activity as a therapeutic modality targeting cancer stem cells of embryonal rhabdomyosarcoma cell line RD.

Rhabdomyosarcoma is the most frequent soft tissue sarcoma in children and adolescents, with a high rate of relapse that dramatically affects the clinical outcome. Multiagent chemotherapy, in combination with surgery and/or radiation therapy, is the treatment of choice. However, the relapse rate is disappointingly high and identification of new therapeutic tools is urgently needed. Under this respect, the selective block of key features of cancer stem cells (CSC) appears particularly promising. In this study, we isolated rhabdomyosarcoma CSC with stem-like features (high expression of NANOG and OCT3/ 4, self-renewal ability, multipotency). Rhabdomyosarcoma CSC showed higher invasive ability and a reduced cytotoxicity to doxorubicin in comparison to native cells, through a mechanism unrelated to the classical multidrug resistance process. This was dependent on a high level of lysosome acidity mediated by a high expression of vacuolar ATPase (V-ATPase). Since it was not associated with other paediatric cancers, like Ewing\u2019s sarcoma and neuroblastoma, V-ATPase higher expression in CSC was rhabdomyosarcoma specific. Inhibition of lysosomal acidification by the V-ATPase inhibitor omeprazole, or by specific siRNA silencing, significantly enhanced doxorubicin cytoxicity. Unexpectedly, lysosomal targeting also blocked cell growth and reduced the invasive potential of rhabdomyosarcoma CSC, even at very low doses of omeprazole (10 and 50 mM, respectively). Based on these observations, we propose lysosome acidity as a valuable target to enhance chemosensitivity of rhabdomyosarcoma CSC, and suggest the use of anti-V-ATPase agents in combination with standard regimens as a promising tool for the eradication of minimal residual disease or the prevention of metastatic disease

Treatment of epilepsy in patients with Alzheimer’s disease

Introduction: Epilepsy is significantly more frequent in AD patients than in age-matched controls, even though the true extent of the phenomenon is not clear yet. Areas covered: In this review, we describe in detail the available data on the pharmacological treatment of epilepsy in patients with AD. We also briefly describe general principles of AEDs use in elderly, as well as the potential cognitive profile of AEDs and safety of concomitant psychotropic drugs in patients with epilepsy and AD. Expertcommentary: As some preclinical data suggest a role of epileptiform discharges in cognitive decline in AD, a prompt diagnosis and treatment of seizures in these patients should be pursued. The few data on the use of AEDs in AD patients suggest that newer AEDs (in particular lamotrigine and levetiracetam) might be good choices. Experimental data even support a potential role of some AEDs in modifying the disease course of AD

Mapping Cortical Degeneration in ALS with Magnetization Transfer Ratio and Voxel-Based Morphometry

Pathological and imaging data indicate that amyotrophic lateral sclerosis (ALS) is a multisystem disease involving several cerebral cortical areas. Advanced quantitative magnetic resonance imaging (MRI) techniques enable to explore in vivo the volume and microstructure of the cerebral cortex in ALS. We studied with a combined voxel-based morphometry (VBM) and magnetization transfer (MT) imaging approach the capability of MRI to identify the cortical areas affected by neurodegeneration in ALS patients. Eighteen ALS patients and 18 age-matched healthy controls were examined on a 1.5T scanner using a high-resolution 3D T1 weighted spoiled gradient recalled sequence with and without MT saturation pulse. A voxel-based analysis (VBA) was adopted in order to automatically compute the regional atrophy and MT ratio (MTr) changes of the entire cerebral cortex. By using a multimodal image analysis MTr was adjusted for local gray matter (GM) atrophy to investigate if MTr changes can be independent of atrophy of the cerebral cortex. VBA revealed several clusters of combined GM atrophy and MTr decrease in motor-related areas and extra-motor frontotemporal cortex. The multimodal image analysis identified areas of isolated MTr decrease in premotor and extra-motor frontotemporal areas. VBM and MTr are capable to detect the distribution of neurodegenerative alterations in the cortical GM of ALS patients, supporting the hypothesis of a multi-systemic involvement in ALS. MT imaging changes exist beyond volume loss in frontotemporal cortices

Acid microenvironment promotes cell survival of human bone sarcoma through the activation of cIAP proteins and NF-κB pathway

Extracellular acidification is a very common cause of stress in tumor microenvironment and of Darwinian pressure. In acid areas of the tumor, most cancer cells are-albeit slowly proliferating-more resistant to cell death than those in well-perfused regions. Tumor acidosis can directly regulate the expression of pro-survival proteins since a low extracellular pH activates the caspase-dependent cell death machinery. This mechanism has never been explored in bone sarcomas. We cultured osteosarcoma and Ewing sarcoma cells under low pH (pH 6.5), and we performed deep-sequencing and protein analysis. Both in in vitro and in vivo models, acidification activity enhanced tumor cells survival. However, we did not observe any change in ERK1 phosphorylation. On the contrary, both at the mRNA and protein level, we found a significant induction of TRAF adaptor proteins and of cIAP proteins (BIRC2 and/or BIRC3). As a consequence, the downstream nuclear transcription factor kappa B (NF-κB) survival pathway was increased. Furthermore, the treatment with the cIAP inhibitor LCL161 reverted the protection from apoptosis under low pH. In vitro results were confirmed both in Ewing sarcoma xenograft and in osteosarcoma patients, since the analysis of tumor tissues demonstrated that the levels of expression of TRAF1 or NF-κB1 significantly correlate with the level of expression of the vacuolar ATPase (V-ATPase), the most important proton pump in eukaryotes. Moreover, in the tissue sections of xenograft model, the nuclear translocation of RelB, a key subunit of the NF-κB transcriptional complex, localized in the tumor region that also corresponded to the acid microenvironment associated with the highest levels of expression of LAMP2 and V-ATPase, in the internal area of the tumor, as revealed by immunohistochemistry. Our data confirm that tumor acid microenvironment activates a stress-regulated switch to promote cell survival of bone sarcoma, and support the hypothesis that this mechanism is mediated by the recruitment of TRAF/cIAP complexes. Altogether, these results suggest that TRAF/cIAP can be considered as a target for anti-cancer therapies

Disolución de rocas carbonatadas: estudio preliminar sobre un proceso de karstificación en los acantilados de Las Grutas, Río Negro

Se tomaron muestras del aguade filtración y de la roca delos acantiladospara realizar análisis químicosy petrográficos,respectivamente.Este estudio, aunque preliminar, demuestra que la roca que constituye la estructura del acantilado se disuelve por efectodel agua circulante en su interior.La recarga del acuífero se produce principalmente por las aguas residuales,cuyo caudal se incrementa en la temporadaestival.Se propone la existencia de un proceso kárstico, caracterizado por la utilización de las aguas residuales por conductos preferentes de la roca del acantilado.Fil: Narvarte, Maite. Universidad Nacional del Comahue. Escuela Superior de Ciencias Marinas. Departamento de Ciencias Marinas; Argentina.Fil: Saad, Juan Francisco. Universidad Nacional del Comahue. Escuela Superior de Ciencias Marinas. Departamento de Ciencias Marinas; Argentina

Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes

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Plasma levels of oxidative stress markers, before and after BoNT/A Treatment, in chronic migraine

The pathophysiological mechanisms of migraine transformation are debated. Modifications of plasma oxidative stress biomarkers have been described in chronic migraine. OnabotulintoxinA (BoNT/A) treatment, approved for chronic migraine prophylaxis, possibly reduces pain neurotransmitters release and oxidative stress products. Aims of our study were to investigate differences in the levels of selected plasmatic oxidative stress biomarkers (Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), Thiolic Groups (SH)) comparing chronic migraineurs (CM) and healthy controls (HC). We also explored possible clinical and biochemical modifications in the CM group after six months of treatment with BoNT/A. At the baseline, we found higher values of AOPP (p < 0.001), and lower values of SH (p < 0.001) and FRAP (p = 0.005) in the CM group. At the six-month follow-up we found a reduction of AOPP (p < 0.001) and an increase of FRAP (p < 0.001) and SH (p = 0.023) within the CM group. BoNT/A treatment improved migraine symptoms in the CM group. We confirmed previous reports of imbalanced antioxidant mechanisms in chronic migraine showing lower antioxidant capacities in patients than controls. BoNT/A improved the levels of plasma oxidative stress biomarkers and confirmed its role as an effective prophylactic treatment for CM. Other studies should investigate the potential antioxidant properties of BoNT/A treatment

COVID-19-Related Myocarditis: Are We There Yet? A Case Report of COVID-19-Related Fulminant Myocarditis

There is increasing evidence of cardiac involvement in COVID-19 cases, with a broad range of clinical manifestations spanning from acute life-threatening conditions such as ventricular dysrhythmias, myocarditis, acute myocardial ischemia and pulmonary thromboembolism to long-term cardiovascular sequelae. In particular, acute myocarditis represents an uncommon but frightening complication of SARS-CoV-2 infection. Even if many reports of SARS CoV-2 myocarditis are present in the literature, the majority of them lacks histological confirmation of cardiac injury. Here, we report a case of a young lady, who died suddenly a few days after testing positive for SARS-CoV-2, whose microscopic and genetics features suggested a direct cardiac involvement compatible with fulminant myocarditis