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Introduction Triple-negative breast cancer (TNBC) is associated with lack of expression of estrogen and progesterone receptors and HER2 and is the subgroup of breast cancers with the worst prognosis. Osteopontin is a phosphorylated glycoprotein whose overexpression may occur in pathological states such as cancers. The main purpose of our study was to evaluate the immunohistochemical expression of osteopontin in connection with the analysis of recognized clinical and pathological prognostic factors in primary sites of TNBC with and without lymph node metastases. Material and methods The immunohistochemical evaluation of osteopontin expression in 35 women with TNBC, chosen from a group of 726 patients, was performed. The material came from the excisional biopsies of primary breast cancers and total mastectomies. Results All patients showed expression of osteopontin, in most cases the expression of osteopontin rated at [+] (57.1%) and [++] (42.9%). Our study analyzed the relationship between the expression of osteopontin and traditional prognostic markers, such as the tumor grade, size, and lymph node involvement. We found a strong relationship only between the expression of osteopontin and the presence of lymph node metastases (p ≤ 0.0001). 93% of patients for whom the expression of osteopontin was determined at [++] had metastasis to lymph nodes and, for comparison, only 15% of women for whom the expression of osteopontin was rated at [+] showed the presence of metastases in the lymphatic nodes. Conclusions There is a correlation between osteopontin expression and the presence of lymph node metastases in TNBC, suggesting that osteopontin plays an important role in the invasiveness of TNBC.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. With the rapid development of radiographic and surgical techniques, resectability decisions are made by a multidisciplinary team. Upfront surgery (Up-S) can improve the survival of patients with potentially resectable disease with the support of adjuvant therapy (AT). However, early recurrences are quite common due to the often-undetectable micrometastases occurring before surgery. Adopted by international consensus in 2017, the standardization of the definitions of resectable PDAC (R-PDAC) and borderline resectable PDAC (BR-PDAC) disease was necessary to enable accurate interpretation of study results and define which patients could benefit from neoadjuvant therapy (NAT). NAT is expected to improve the resection rate with a negative margin to provide significant local control and eliminate micrometastases to prolong survival. Providing information about optimal sequential multimodal NAT seems to be key for future studies. This article presents a multidisciplinary concept for the therapeutic management of patients with R-PDAC and BR-PDAC based on current knowledge and our own experience.

Purpose: Cancer cells, despite stemming from the own cells of their host, usually elicit an immune response. This response usually enables elimination of cancer at its earliest stages. However, some tumors develop mechanisms of escaping immune destruction and even profiting from tumor-derived inflammation., Methods: We summarized the roles of different immune cell populations in various processes associated with cancer progression and possible methods of reshaping tumor-associated inflammation to increase the efficacy of cancer therapy., Results: Changes in various signaling pathways result in attraction of immunosuppressive, pro-tumorigenic cells, such as myeloid-derived suppressor cells, tumor-associated macrophages, and neutrophils, while at the same time suppressing the activity of lymphocytes, which have the potential of destroying cancer cells. These changes promote tumor progression by increasing angiogenesis and growth, accelerating metastasis, and impairing drug delivery to the tumor site., Conclusion: Due to its multi-faceted role in cancer, tumor-associated inflammation can serve as a valuable therapy target. By increasing it, whether through decreasing overall immunosuppression with immune checkpoint inhibitor therapy or through more specific methods, such as cancer vaccines, oncolytic viruses, or chimeric antigen receptor T cells, cancer-derived immunosuppression can be overcome, resulting in immune system destroying cancer cells. Even changes occurring in the microbiota can influence the shape of antitumor response, which could provide new attractive diagnostic or therapeutic methods. Interestingly, also decreasing the distorted tumor-associated inflammation with non-steroidal anti-inflammatory drugs can lead to positive outcomes., (© 2022. The Author(s).)

Pancreatic cancer (PC) is the seventh leading cause of cancer death across the world. Poor prognosis of PC is associated with several factors, such as diagnosis at an advanced stage, early distant metastases, and remarkable resistance to most conventional treatment options. The pathogenesis of PC seems to be significantly more complicated than originally assumed, and findings in other solid tumours cannot be extrapolated to this malignancy. To develop effective treatment schemes prolonging patient survival, a multidirectional approach encompassing different aspects of the cancer is needed. Particular directions have been established; however, further studies bringing them all together and connecting the strengths of each therapy are needed. This review summarises the current literature and provides an overview of new or emerging therapeutic strategies for the more effective management of metastatic PC.

The most common tumour of the pancreas is ductal adenocarcinoma (PDAC). It remains one of the most lethal non-neuroendocrine solid tumours despite the use of a multi-approach strategy. Other, less-common neoplasms, which are responsible for 15% of pancreatic lesions, differ in treatment and prognosis. Due to the low incidence rate, there is a lack of information about the rarest pancreatic tumours. In this review, we described six rare pancreatic tumours: intraductal papillary mucinous neoplasm (IPMN), mucinous cystadenoma (MCN), serous cystic neoplasm (SCN), acinar cell carcinoma (ACC), solid pseudopapillary neoplasm (SPN) and pancreatoblastoma (PB). We distinguished their epidemiology, clinical and gross features, covered the newest reports about courses of treatment and systematised differential diagnoses. Although the most common pancreatic tumour, PDAC, has the highest malignant potential, it is still essential to properly classify and differentiate less-common lesions. It is vital to continue the search for new biomarkers, genetic mutations and the development of more specific biochemical tests for determining malignancy in rare pancreatic neoplasms.

Pancreatic cancer is the malignant disease with the highest mortality rate, and it ranks third in the world after lung and colon cancer. Identified factors that increase the risk of developing pancreatic cancer include chronic pancreatitis, radiation therapy to the pancreatic area due to another cancer, diabetes mellitus, obesity, smoking, and age. The objective of this study was to present the current state of knowledge on the quality of life of patients diagnosed with pancreatic cancer, factors that determine QoL, and ways of coping with the disease. The low curability and low survival rates of pancreatic cancer significantly affect the quality of life of patients, often in the form of significant deterioration, especially in terms of mental changes, cognitive functions, and coping with the disease. Cognitive decline with comorbid depression is also typical for patients with this type of cancer. Research has shown that the health-related quality of life of patients with pancreatic cancer is low, so further research is needed to improve the situation in this area.

Background: pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related deaths with increasing incidence and link to the onset of diabetes mellitus (DM). The aim of this study is to describe the prevalence of DM among patients with the diagnosis of PDAC, analyse the association between the occurrence of DM and clinicopathological factors, and detect variables influencing overall survival., Methods: a retrospective analysis of medical records was performed. The patients were divided into non-DM ( n = 101) and DM ( n = 74) groups. Statistical analysis with the usage of appropriate tests was conducted., Results: Patients in the groups of DM and NODM had significantly longer median OS than the non-DM group. Nodal involvement, tumour location, level of CEA, CRP and CRP/lymphocytes ratio were significantly associated with OS among patients with any type of DM. Neutropenia was less frequently observed in the DM group., Conclusions: DM is prevalent among patients with pancreatic cancer. In our study, patients with DM receiving palliative chemotherapy had significantly higher median OS than those without DM. The increased comprehension of the mechanisms of the relationship between DM and pancreatic cancer needs further research, which might provide avenues for the development of novel preventive and therapeutic strategies.

BRCA1-mutated breast cancer (BC) is responsible for approximately 25% of hereditary breast cancer cases. BRCA1 is a tumor suppressor protein regulating the cell cycle and DNA repair; therefore its dysfunctions play a significant role in carcinogenesis. BRCA1-mutated BC is associated with basal-like phenotype, lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in addition to frequent TP53 mutations and poor prognosis. Currently used criteria for genetic evaluation of BC for the risk of hereditary mutations are based on patients' age and family history, and therefore are prone to be imprecise or incomplete. This review discusses recently developed sets of immunohistochemical markers, promising independent markers (nestin, ALDH1, FOXO3, claudins, topoisomerase 1, EGFR) and their potential to be incorporated into clinical practice as a support tool in oncological counseling. This approach could be applied as a screening method for cost-effective selection of cases requiring genetic testing or adapted in pathology laboratories with limited access to molecular techniques. Although not all of the described predictor models have been validated yet, they could further improve the performance of BRCA1 screening methods in BC in the near future via increasing the accuracy of criteria for further genetic evaluation.

We analyzed the operative measures that may be used to reduce the likelihood of sagittal syndesmotic malreduction. Hence, we propose a simple technical tip to avoid sagittal plane malreduction of the fibula within the syndesmosis in ankle fractures. Supporting the leg under the heel should be avoided when performing syndesmotic reduction for unstable malleolar fractures, and support under the calf should be used instead. Our observations have been confirmed in 6 cadaver specimens. We observed that there was a significant anterior subluxation of the fibula when the leg was supported under the heel. No significant difference between the intact and unstable state was present when the leg was supported under the calf. In conclusion, during syndesmotic reduction and fixation in supine position, supporting the foot under the heel should be avoided.

Introduction: The genetic Lauge-Hansen classification has been traditionally used for reconstruction of the mechanism of ankle injury. The ability of the Lauge-Hansen classification to predict actual mechanism of the injury has been questioned in recent studies, leaving a void in medicolegal reasoning. The aim of this study is to identify morphologic features of malleolar fractures on plain X-rays that may be used to reveal the fracture mechanism., Material and Methods: Radiographs of 78 patients with acute malleolar fractures were analyzed and compared with fracture mechanisms reported by these patients., Results: A modified Pankovich classification of medial malleolus fractures and the presence of a posterior malleolus fracture were able to significantly predict the mechanism of fracture reported by the patient (p<0.05). Lateral fracture morphology was not useful for predicting the fracture mechanism except for infrasyndesmotic fractures pointing to a supination mechanism., Conclusion: A supination mechanism of the fracture can be predicted by observing pure ligamentous or chip-avulsion deltoid injury. The presence of an anterior colliculus fracture of the medial malleolus is correlated with a pronation mechanism. A fracture of the posterior malleolus correlates with pronation while an intact posterior malleolus correlateds with supination as a fracture mechanism. Absolute determination of fracture mechanism from the X-ray morphology of the fracture is impossible in the majority of cases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The genetic Lauge-Hansen classification is used for reconstruction of the mechanism of ankle injury. In this study, we addressed the question of agreement between the mechanism of the fracture as postulated by the Lauge-Hansen classification and mechanism reported by the patient in rotational ankle fractures., Material and Methods: Radiographs of 78 patients with acute malleolar fractures were analyzed and compared with fracture mechanisms reported by these patients., Results: The patient reported mechanisms were in concordance with the mechanism deducted from the X-rays in 49% of cases. Only 17% of patients who recalled a pronation trauma actually had radiographs classified as pronation fractures while 76% of patients who recalled a supination trauma were also radiographically classified as having sustained supination type fractures., Conclusion: The Lauge-Hansen classification should be used with caution for determining the actual mechanism of injury as it was able to predict the patient reported fracture mechanism in less than 50% of cases. A substantial percentage of fractures appearing radiographically as supination type injuries may have been actually produced by a pronation fracture mechanism., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Objectives: Pathological alterations of glutamatergic systems were observed in neurodegenerative and psychiatric disorders. There is some evidence that this system may be involved in the genetic vulnerability to suicide. The aim of the present study was to analyze possible relationship between the GRIN2B polymorphism and suicidal behavior. We hypothesized that this genetic factor may be associated with suicide attempts in alcohol-dependent patients and with death by suicide., Methods: To analyze the relationship between GRIN2B and suicide attempts, the selected rs2268115 polymorphism was genotyped in a sample of 345 alcohol-dependent individuals stratified by the history of suicide attempts. The second part of the study concerning suicide was based on a sample of 510 suicide victims and 450 controls., Results: The frequency of rs2268115 G allele among alcohol-dependent patients with the history of suicide attempts was significantly higher than among non-suicidal alcohol-dependent individuals (OR = 1.45, p = .033). This association was more significant when analyzing alcohol-dependent patients only without co-occurring drug dependence (OR = 1.62, p = .021). The analyzed GRIN2B polymorphism was associated with a twofold increase in odds of a suicide attempt (OR = 2.01, p = .004). No relationships between rs2268115 and death by suicide were identified., Discussion and Conclusions: Our results suggest that glutamatergic system influence susceptibility to suicide attempts in alcohol-dependent individuals. Suicidal behavior and alcohol dependence may share a common etiology related to the glutamatergic system., Scientific Significance: The major contribution of the present study is a novel finding of the possible association between GRIN2B rs2268115 polymorphism and suicide attempts in alcohol-dependent individuals. (Am J Addict 2017;26:595-601)., (© 2017 American Academy of Addiction Psychiatry.)

Cyanides are infamous for their highly poisonous properties. Accidental cyanide poisoning occurs frequently, but occasionally, intentional poisonings also occur. Inhalation of fumes generated by fire may also cause cyanide poisoning. There are many limitations in direct analysis of cyanide. 2-Aminothiazoline-4-carboxylic acid (ATCA), a cyanide metabolite, seems to be the only surrogate that is being used in the detection of cyanide because of its stability and its cyanide-dependent quality in a biological matrix. Unfortunately, toxicokinetic studies on diverse animal models suggest significant interspecies differences; therefore, the attempt to extrapolate animal models to human models may be unsuccessful. The aim of the present study was to evaluate the use of ATCA as a forensic marker of cyanide exposure. For this purpose, post-mortem materials (blood and organs) from fire victims (n = 32) and cyanide-poisoned persons (n = 3) were collected. The distribution of ATCA in organs and its thermal stability were evaluated. The variability of cyanides in a putrid sample and in the context of their long-term and higher temperature stability was established. The presence of ATCA was detected by using an LC-MS/MS method and that of cyanide was detected spectrofluorimetrically. This is the first report on the endogenous ATCA concentrations and the determination of ATCA distribution in tissues of fire victims and cyanide-poisoned persons. It was found that blood and heart had the highest ATCA concentrations. ATCA was observed to be thermally stable even at 90 °C. Even though the cyanide concentration was not elevated in putrid samples, it was unstable during long-term storage and at higher temperature, as expected. The relationship between ATCA and cyanides was also observed. Higher ATCA concentrations were related to increased levels of cyanide in blood and organs (less prominent). ATCA seems to be a reliable forensic marker of exposure to lethal doses of cyanide.

Background: Airway management is a crucial skill essential to paramedics and personnel working in Emergency Medical Services and Emergency Departments: Lack of practice, a difficult airway, or a trauma situation may limit the ability of paramedics to perform direct laryngoscopy during cardiopulmonary resuscitation. Videoscope devices are alternatives for airway management in these situations. The ETView VivaSight SL (ETView; ETView Ltd., Misgav, Israel) is a new, single-lumen airway tube with an integrated high-resolution imaging camera. To assess if the ETView VivaSight SL can be a superior alternative to a standard endotracheal tube for intubation in an adult cadaver model, both during and without simulated CPR., Methods: ETView VivaSight SL tube was investigated via an interventional, randomized, crossover, cadaver study. A total of 52 paramedics participated in the intubation of human cadavers in three different scenarios: a normal airway at rest without concomitant chest compression (CC) (scenario A), a normal airway with uninterrupted CC (scenario B) and manual in-line stabilization (scenario C). Time and rate of success for intubation, the glottic view scale, and ease-of-use of ETView vs. sETT intubation were assessed for each emergency scenario., Results: The median time to intubation using ETView vs. sETT was compared for each of the aforementioned scenarios. For scenario A, time to first ventilation was achieved fastest for ETView, 19.5 [IQR, 16.5-22] sec, when compared to that of sETT at 21.5 [IQR, 20-25] sec (p = .013). In scenario B, the time for intubation using ETView was 21 [IQR, 18.5-24.5] sec (p < .001) and sETT was 27 [IQR, 24.5-31.5] sec. Time to first ventilation for scenario C was 23.5 [IQR, 19-25.5] sec for the ETView and 42.5 [IQR, 35-49.5] sec for sETT., Conclusions: In normal airways and situations with continuous chest compressions, the success rate for intubation of cadavers and the time to ventilation were improved with the ETView. The time to glottis view, tube insertion, and cuff block were all found to be shorter with the ETView., Trial Registration: clinicaltrials.gov Identifier: NCT02733536.

Objective: The aim of the trial was to compare the time parameters for intubation with the use of the Macintosh (MAC) laryngoscope and Pentax AWS-S100 videolaryngoscope (AWS; Pentax Corporation, Tokyo, Japan) with and without chest compression (CC) by paramedics during simulated cardiopulmonary resuscitation in a cadaver model., Methods: This was a randomized crossover cadaver trial. Thirty-five paramedics with no experience in videolaryngoscopy participated in the study. They performed intubation in two emergency scenarios: scenario A, normal airway without CC; scenario B, normal airway with continuous CC., Results: The median time to first ventilation with the use of the AWS and the MAC was similar in scenario A: 25 (IQR, 22-27) seconds vs. 24 (IQR, 22.5-26) seconds (P=.072). A statistically significant difference in TTFV between AWS and MAC was noticed in scenario B (P=.011). In scenario A, the first endotracheal intubation (ETI) attempt success rate was achieved in 97.1% with AWS compared with 94.3% with MAC (P=.43). In scenario B, the success rate after the first ETI attempt with the use of the different intubation methods varied and amounted to 88.6% vs. 77.1% for AWS and MAC, respectively (P=.002)., Conclusions: The Pentax AWS offered a superior glottic view as compared with the MAC laryngoscope, which was associated with a higher intubation rate and a shorter intubation time during an uninterrupted CC scenario. However, in the scenario without CC, the results for AWS and MAC were comparable., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: Medical personnel may encounter difficulties in obtaining intravenous (IV) access during cardiac arrest. The 2015 American Heart Association guidelines and the 2015 European Resuscitation Council guidelines for cardiopulmonary resuscitation (CPR) suggest that rescuers establish intraosseous (IO) access if an IV line is not easily obtainable.The aim of the study was to compare the success rates of the IO proximal tibia and proximal humerus head access performed by paramedics using the New Intraosseous access device (NIO; Persys Medical, Houston, TX, USA) in an adult cadaver model during simulated CPR.In an interventional, randomized, crossover, single-center cadaver study, a semi-automatic spring-load driven NIO access device was investigated. In total, 84 paramedics with less than 5-year experience in Emergency Medical Service participated in the study. The trial was performed on 42 adult cadavers. In each cadaver, 2 IO accesses to the humerus head, and 2 IO accesses to the proximal tibia were obtained.The success rate of the first IO attempt was 89.3% (75/84) for tibial access, and 73.8% (62/84) for humeral access (P = 0.017). The procedure times were significantly faster for tibial access [16.8 (interquartile range, IQR, 15.1-19.9] s] than humeral access [26.7 (IQR, 22.1-30.9) s] (P < 0.001).Tibial IO access is easier and faster to put in place than humeral IO access. Humeral IO access can be an alternative method to tibial IO access., Trial Registration: clinicaltrials.gov Identifier: NCT02700867.

Postmortem computed tomography (PMCT) is gaining popularity in forensic medicine. Computed tomography routinely performed in clinical medicine involves intravenous contrast administration. Unfortunately, postmortem examinations are typically limited to uncontrasted CT scans, where blood vessels and their potential injury sites are invisible. One serious problem is the fact that due to the process of decomposition, contrast agents used for vessel visualization in the living cannot be used in cadavers. Therefore, a special contrast agent designed for cadavers has been developed. This contrast agent has a high density and is lipophilic. Its use ensures very good visualization of blood vessels it is, however, associated with high costs and may alter findings of a later histopathological examination. This study presents early experience with the air as negative contrast agent to enhance all blood vessels in the body. The carbon dioxide (CO2) gas has been used as a contrast agent in live individuals with contraindications against the use of iodinated contrast. In corpses with advanced postmortem changes, putrefaction gases also considerably enhance the visibility of blood vessels and organs they fill. There have also been some positive effects with the use of gas in postmortem angiography of coronary vessels. These findings encouraged us to attempt air administration via catheters introduced into the femoral artery or a central venous access site in the superior vena cava. The gas distributed easily throughout the body and surprisingly well contrasted both arteries and veins of various caliber. The presence of the air administered into vessels did not cause any apparent, significant alterations in autopsy findings. Although optimization of the gas administration technique requires further studies, we can already say that this is a promising direction in postmortem angiography., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

2-aminothiazoline-4-carboxylic acid (ATCA) is a hydrogen cyanide metabolite that has been found to be a reliable biomarker of cyanide poisoning, because of its long-term stability in biological material. There are several methods of ATCA determination; however, they are restricted to extraction on mixed mode cation exchange sorbents. To date, there has been no reliable method of ATCA determination in whole blood, the most frequently used material in forensic analysis. This novel method for ATCA determination in post mortem specimen includes protein precipitation, and derivatization of interfering compounds and their later extraction with ethyl acetate. ATCA was quantitatively analyzed via high performance liquid chromatography-tandem mass spectrometry with positive electrospray ionization detection using a hydrophilic interaction liquid chromatography column. The method satisfied all validation criteria and was tested on the real samples with satisfactory results. Therefore, this analytical approach has been proven to be a tool for measuring endogenous levels of ATCA in post mortem specimens. To conclude, a novel, accurate and sensitive method of ATCA determination in post mortem blood was developed. The establishment of the method provides new possibilities in the field of forensic science., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis leads to impaired stress response. FK506-binding protein 51 (FKBP5), which influences HPA axis activity via glucocorticoid receptors, is supposed to play an important role in the regulation of negative feedback and glucocorticoid resistance. Since ineffective stress response mechanisms are considered as a biological background of suicide behavior, we aimed to analyze a possible association between FKBP5 functional polymorphisms and completed suicide., Methods: The selected FKBP5 polymorphisms rs1360780 and rs3800373 were genotyped in a sample of 563 suicide victims and 475 controls., Results: A significant association between the high-induction rs3800373 C allele and completed suicide was detected (OR = 1.36, p = 0.007). In this polymorphism, genotype distribution supported a codominant model of inheritance. The analyzed SNPs were in strong linkage disequilibrium (D' = 0.916 and r2 = 0.826) with the rs1360780 (T)-rs3800373 (C) haplotype apparently responsible for the observed association (OR = 1.34, p = 0.010)., Conclusion: The results of the present study indicate that genetic alterations in FKBP5 may influence vulnerability to suicide., (© 2015 S. Karger AG, Basel.)

Objectives: To expand the anatomical investigations of the G-spot and to assess the G-spot's characteristic histological and immunohistochemical features., Design: An observational study., Setting: International multicentre., Population: Eight consecutive fresh human female cadavers., Methods: Anterior vaginal wall dissections were executed and G-spot microdissections were performed. All specimens were stained with haematoxylin and eosin (H&E). The tissues of two women were selected at random for immunohistochemical staining., Main Outcome Measures: The primary outcome measure was to document the anatomy of the G-spot. The secondary outcome measures were to identify the histology of the G-spot and to determine whether histological samples stained with H&E are sufficient to identify the G-spot., Results: The anatomical existence of the G-spot was identified in all women and was in a diagonal plane. In seven (87.5%) and one (12.5%) of the women the G-spot complex was found on the left or right side, respectively. The G-spot was intimately fused with vessels, creating a complex. A large tangled vein-like vascular structure resembled an arteriovenous malformation and there were a few smaller feeding arteries. A band-like structure protruded from the tail of the G-spot. The size of the G-spot varied. Histologically, the G-spot was determined as a neurovascular complex structure. The neural component contained abundant peripheral nerve bundles and a nerve ganglion. The vascular component comprised large vein-like vessels and smaller feeding arteries. Circular and longitudinal muscles covered the G-complex., Conclusion: The anatomy of the G-spot complex was confirmed. The histology of the G-spot presents as neurovascular tissues with a nerve ganglion. H&E staining is sufficient for the identification of the G-spot complex., (© 2014 Royal College of Obstetricians and Gynaecologists.)

The A allele of rs9939609 in the FTO gene predisposes to increased body mass index (BMI) and obesity. Recently we showed an inverse association between the obesity related A allele of rs9939609 and alcohol dependence which was replicated by others. Since this finding raises a possibility that FTO may be associated with other psychiatric phenotypes, we aimed to examine association of rs9939609 with completed suicide. We genotyped rs9939609 in 912 suicide victims and 733 controls using TaqMan approach. We observed an inverse association between suicide and the rs9939609 A allele (OR = 0.80, P = 0.002, Pcor = 0.006) with genotype distribution suggesting a co-dominant effect. Given the link between alcoholism and suicide under influence of alcohol reported in Polish population, confounding by alcohol addiction was unlikely due to apparently similar effect size among cases who were under influence of ethanol at the time of death (OR = 0.76, P = 0.003, N = 361) and those who were not (OR = 0.80, P = 0.007, N = 469). The search for genotype-phenotype correlations did not show significant results. In conclusion, our study proves that there is an inverse association between rs9939609 polymorphism in FTO gene and completed suicide which is independent from association between FTO and alcohol addiction.

Background: rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide., Methods: We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians., Results: We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR  =  1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019)., Conclusions: In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol.

MTHFR C677T polymorphism (rs1801133) was associated with numerous psychiatric conditions but no prior study investigated whether it predisposes to completed suicide. We typed rs1801133 in 692 suicide victims and 3257 controls representative of a Polish adult population (the WOBASZ cohort). Although we had a power of 0.8 to detect (at alpha 0.05) an allelic OR=1.19, we did not find significant difference among suicides vs. controls in the prevalence of the MTHFR 677T allele (OR=1.02, p=0.759) or the TT genotype (OR=1.01, p=0.926). Since among controls we found an association between TT and depression defined by Beck Depression Inventory (BDI, OR=1.61, p=0.049) we also compared suicides with controls without signs of depression (BDI ≤ 11) but found no association (OR=1.0, p=0.976). Analyses within suicides showed trends (not significant after Bonferroni correction) for correlations between the dose of the T allele and age at death among males and blood ethanol concentration among females, who committed suicide under the influence of alcohol. We conclude that MTHFR C677T polymorphism is not a risk factor for completed suicide. The sex-specific trends for correlations between rs1801133 and age at death, and blood ethanol concentration should be studied further., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: We hypothesized that DNA variants affecting neurodevelopment such as rs4307059 (CDH10/CDH9), rs930752 (NRXN1), rs6265 (BDNF) or rs10868235 (NTRK2) may predispose to completed suicide., Methodology: We used a case-control two-stage approach based on a discovery cohort (557 cases and ∼550 controls) and replication cohort (159 cases and 186 controls). The suicides were ascertained as consecutive cases autopsied at the Department of Forensic Medicine, Medical University of Warsaw, Poland., Results: In the discovery cohort we found an association between suicide and the CC genotype in the rs4307059 polymorphism (OR 1.64, p = 0.012). The trend for an overrepresentation of the CC homozygotes among suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in the pooled cohorts showed that rs4307059 CC was associated with completed suicide (OR 1.71, p = 0.002) also after Bonferroni correction (p(cor.) = 0.024). In an exploratory search for genotype-phenotype correlation we found that males with the rs4307059 CC genotype committed suicide earlier than those with CT/TT genotypes (p = 0.049)., Conclusions: The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort., (Copyright © 2012 S. Karger AG, Basel.)

Background: The pulmonary artery catheter provides most hemodynamic informations, which are necessary for the patient monitoring during liver transplantation. However, its application may be associated with complications., Case Report: Authors present a case of unexpected right ventricular rupture during liver transplantation in a 53-year-old male, with end-stage liver disease secondary to hepatitis C virus and alcohol abuse. The most likely cause of this complication was myocardial scarification of right ventricle during introducer sheath inserting. There was six hours period between vessel cannulation and the first signs of heart failure, which occurred in the final anhepatic phase. Attempts to surgical repair of damaged heart wall failed and the patient died., Conclusions: Based on the present case analysis we suggest to restrict the introduction depth of dilatator and possibly shorten it 2-3 cm by the manufacturer. We should also note that time elapsed from the vessel cannulation to cardiac tamponade first signs does not preclude this procedure as a cause of this fatal complications.

The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in controls (17.5% vs. 8.6%; p = 0.02), particularly in those with a history of repeated suicide attempts (53.3% vs. 8.6%; p < 0.0001). The examined TPH2 polymorphism was found to be associated with suicide. This genetic marker may be particularly important in understanding risk of multiple suicide attempts. Further analyses are needed to confirm these results.

Many authors have questioned the gross anatomy of the septal papillary muscle of the conus known as the papillary muscle complex (PMC) during the past century. An anatomical investigation was conducted to identify the morphology and the topography of the PMC. Our study involved 200 formalin fixed adult human hearts. The PMC was present in 82% of the hearts, while in the remaining 18% of specimens, it was replaced by tendinous chords. The PMC was connected with the septal (59.7%), anterior (20.7%), or both septal and anterior leaflets (19.5%) with single (29.8%) or multiple chordae tendinae (70.1%). The PMC was also found to be present as a single papilla (51.8%), double papilla (32.9%) or triple papilla (15.2%). In addition to the PMC, we observed accessory single septal papillary muscles 42 specimens, double septal papillary muscles 32 specimens and triple septal papillary muscles 26 specimens. In the right ventricular inflow tract, the location of the PMC was consistently found to be in a position below the junction of the anterior and septal leaflets of the tricuspid valve. In the right ventricular outflow tract, we were able to identify 73 specimens in which the PMC was located at the junction formed superiorly by the inferior border of the subpulmonary infundibulum and inferiorly by the superior-lateral border of the septal band, extending into the region of the subpulmonary infundibulum. In the remaining 27%, the PMC was located primarily at the area occupied by the superiolateral border of the septal band without extending to the subpulmonary infundibulum. The present study describes the topography of the PMC according to its surrounding anatomical structures such as the tricuspid valve, subpulmonary infundibulum and septal band of the right ventricle. This anatomical data could have important clinical significance for cardiac surgeons operating in this area.

Aims: Despite the large number of suicides that occur with intoxication, little is known about the unique predictors of suicide after alcohol consumption. The goal of this study was to examine clinical and genetic risk factors for alcohol-related suicide., Methods: Data on 162 suicide victims were obtained from post-mortem examinations, police and prosecution inquiries, autopsy protocols and available medical records. Four single nucleotide polymorphisms in the central serotonin system and the renin-angiotensin system related genes previously found to be associated with suicide, alcohol dependence or depression were genotyped., Results: The strongest predictor of suicide under the influence of alcohol was alcohol dependence (OR = 4.63). Those who did not drink alcohol before suicide were more likely to have a diagnosis of major depressive disorder in their medical record and more often had the TT genotype of the tryptophan hydroxylase 2 gene., Conclusions: Suicide under the influence of alcohol is strongly connected with alcohol dependence. The TPH2 gene may play an important role in suicide vulnerability especially in individuals who did not drink alcohol before suicide.

Background/aims: An association between the II genotype of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and suicide was found among Japanese men. Our purpose was to replicate this finding in Caucasians and explore other putative genotypic associations among suicides., Methods: The ACE genotypes were studied by a 2-stage PCR method in 150 completed suicides and 165 age- and sex-matched controls., Results: We found an increase in the frequency of the ACEI allele among male victims of suicide compared to male controls (odds ratio, OR = 1.69, p < 0.006), female suicides (OR = 2.01, p = 0.006) and pooled controls (OR = 1.77, p = 0.001). Analysis of genotype distribution showed that the codominant model had the best fit (p = 0.7) whereas the recessive model could be rejected (p = 0.04). Among males we found an association between the number of the ACE I allele and the method of suicide: OR = 17.98, p(corrected) = 0.00003, for jumping from a height; OR = 0.36, p(corrected) = 0.048, for hanging. We also observed a trend for a negative effect of the number of copies of the ACE I allele on prevalence of depression (OR = 0.36, p = 0.013) and a trend for an effect on age at death (p = 0.021)., Conclusions: Our results suggest that low ACE activity associated with the I allele is a risk factor for suicide, especially in a subset of males. This may be of concern given the widespread use of drugs lowering ACE activity., (Copyright 2009 S. Karger AG, Basel.)

False tendons (FTs) have been extensively described and recognized by gross anatomic studies. However, in the clinical setting the recognition of FTs is limited to the use of echocardiography. We examined 200 formalin fixed adult hearts, with gross dissections. In addition, 90 of these specimens were also examined with ultrasonographic and endoscopic techniques. Gross examination was able to identify FTs in 128 (62%) specimens. The total number of FTs observed, was 248 and was classified into five types according to their location. In Type I (92, 37.1%) the FT was located between the posteromedial papillary muscle and the ventricular septum. In Type II (55, 22.1%) the FT was located between the two papillary muscles. Type III (41, 16.5%) was classified as an FT between the anterolateral papillary muscle and the ventricular septum. The FT in Type IV (31, 12.5%) was observed to connect between the ventricular septum and the free wall and lastly in Type V (29, 11.6%) the FTs were found to be weblike with three or more points of insertion. When using all three techniques (n = 90), gross dissection and endoscopy were able to identify FTs in 62.2% of specimens while echocardiographic imaging was only able to identify FTs in 27.7% of specimens. Of the 114 FTs detected grossly and endoscopically, echocardiography was only able to identify 46 (40.3%). Therefore, the overall sensitivity of echocardiography for detecting left ventricular FTs was only 40.3%, compared to 100% for endoscopy. Based upon the ability or lack thereof of echocardiography to detect certain topographical patterns, we have created a small series of subtypes for the FTs. Histologically, in 30% of the FTs, conduction tissue fiber was observed to be present, which may implicate them in the appearance of arrhythmias.

The heart is a muscular organ supported by collagenous tissue. The collagenous tissue is condensed in certain areas to form a supporting framework, often called the fibrous skeleton. The so-called tendon of the infundibulum has previously been described as part of this skeleton, but its structure and incidence remain ill defined. The tendon was initially described as a strip of fibrous tissue running between the aortic root and the pulmonary trunk. Since information on its structure is vague, we sought to evaluate its existence in 100 formalin-fixed adult human hearts obtained from subjects ranging in age from 22 to 86 years, in 20 hearts from infants and children aged from 2 months to 6 years at the time of their death and in 10 cattle hearts. We used classical macroscopic anatomical techniques to demonstrate all the possible connections between the sinuses of the aorta and the pulmonary trunk. We then supplemented the macroscopic techniques with serial transverse histological sections taken through the vascular roots, staining the sections with the haematoxylin-eosin, van Gieson, Masson trichrome and orcein staining methods. Fascial bands surrounded by connective tissue were observed in all hearts. In 80 adult hearts and in 16 neonatal hearts we found fascial bands or strips, which connected the aortic and pulmonary roots. Only in two hearts, however, were we able to identify tendon-like structures, and histology revealed that these were formed by tightly packed collagen fibres intermingled with fat, most likely due to advanced age. Thus in those cases where a "tendon" was present it was no more than condensed fascial bands joining together the apposing sinuses of the arterial trunks. In our opinion, therefore, accounts in the literature describing the "tendon of the infundibulum" as a tendinous structure connecting the aortic and pulmonary roots do not accurately represent this anatomical structure.

The retro-oesophageal right subclavian artery is an anatomical abnormality encountered by anatomists and pathologists and, more recently, interventional cardiologists and thoracic surgeons with an incidence of 0.2-2% in the population. We report a case of a retrotracheal right subclavian artery which originated distally along the left aortic arch and coursed between the trachea and the oesophagus. Additionally, the aortic arch gave rise to a common trunk, which subsequently bifurcated to yield to a right vertebral artery and a left thyroidea ima, replacing the left inferior thyroid artery. Consequently the right and the left recurrent laryngeal nerves were found to recur normally. The possible embryonic development of these branching patterns and their clinical significance is discussed.

Myocardial bridging is recognized as an anatomical variation of the human coronary circulation in which an epicardial artery lies in the myocardium for part of its course. Thus, the vessel is 'bridged' by myocardium. The anterior interventricular branch of the left coronary artery has been reported as the most common site of myocardial bridges but other locations have been reported. The purpose of this study was to provide more definitive information on the vessels with myocardial bridges, the length and depth of the bridged segment, and the relationship between the presence of bridges and coronary dominance. Two hundred formalin-fixed human hearts were examined. Myocardial bridges were found in 69 (34.5%) of the hearts with a total of 81 bridges. One bridge was found in 59 of these hearts and multiple bridges were observed in ten (eight with double bridges and two with triple bridges). Bridges were most often found over the anterior interventricular artery (35 hearts). Bridges were also found over the diagonal branch of the left coronary artery (14), over the left marginal branch (five) and over the inferior interventricular branch of the left coronary artery (six). Bridges were also found over the right coronary artery (15 hearts), over the right marginal branch (four) and over the inferior interventricular branch of the right coronary artery (two). The presence of bridges appeared to be related to coronary dominance, especially in the left coronary circulation. Forty-six (66.6%) of the hearts with bridges were left dominant. Forty-two of these had bridges over the left coronary circulation and four over the right coronary circulation. Seventeen hearts (24.6%) were right dominant. Eleven of these had bridges over the right coronary circulation and six over the left coronary circulation. The remaining six hearts were co-dominant with four having bridges over the left coronary circulation and two over the right coronary circulation. The mean length of the bridges was 31 mm and the mean depth was 12 mm. The possible clinical implications of myocardial bridging may vary from protection against atherosclerosis to systolic vessel compression and resultant myocardial ischaemia.

The retroesophageal right subclavian artery is an anatomical abnormality encountered by anatomists and pathologists and recently interventional cardiologists and thoracic surgeons have also come across this phenomenon. We report a case of a retroesophageal right subclavian artery arising from a normally located left aortic arch in a young male autopsied in the Department of Forensic Service of Warsaw Medical University. In addition to the aforementioned anomaly, the presence of a right non-recurrent inferior laryngeal nerve was noticed. The possible embryonic development of these branching patterns and their clinical significance is discussed.

The heart, as we know, is a muscular tissue supported by collagenous structures forming the fibrous skeleton of the heart. A structure by the name of the tendon of infundibulum appeared in the literature with no definite information about its structure or even its existence. The tendon of infundibulum was described as a strip of fibrous tissue structure situated between the aortic root and pulmonary trunk. Our study involved 30, formalin fixed, adult human hearts ranging from 18 to 81 years. Classical macroscopic anatomical methods were applied to observe macroscopically all the connections between the aorto-pulmonary trunk, together with serial transverse histological sections, through roots of the aorta and pulmonary trunk, using eosin-hematoxylin and van Gieson staining. All the hearts seemed to encompass many fascial bands attended by connective tissue. However these fascial bands are not concrete structures and cannot be termed tendons. In our investigation we have been unable to demonstrate macroscopically or histologically any structure which could be significantly approximating to the initial description of the literature. However, as far as we are able to judge, the term tendon of infundibulum has erroneously been introduced into many medical textbooks since the literature cannot still prove its existence.