Incidence, risk factors and potential timing of occurrence of pulmonary embolism in fatal trauma: An autopsy based case-control study on 2705 victims.

BACKGROUND: Pulmonary embolism (PE) following trauma is a potentially preventable but highly lethal complication. We sought to investigate the incidence, risk factors and potential timing of occurrence of post-traumatic PE in a large cohort of trauma fatalities. METHODS: A case-control study on 9266 consecutive trauma fatalities (between 1996 and 2005) from a regional autopsy-based trauma registry. Injuries were classified according to the Abbreviated Injury Scale-1990 edition (AIS-90) and the Injury Severity Score (ISS) was calculated. Hospitalized victims were categorized according to the presence or absence of PE on autopsy. Univariate comparisons and multivariate logistic regression analysis for probabilities of association (odds ratios-OR) were performed. RESULTS: Out of 2705 subjects who met the inclusion criteria, 116 had autopsy findings of PE and constituted the PE group (incidence of 4,3%), while the remaining victims formed the control group. The survival time of the PE group ranged from 0.66 to 104.73 days. Victims in the PE group were older (median age 69.5 vs 59), had lower ISS values (median 16 vs 26) and longer post-injury survival times (median 13.6 vs 5.7 days). Positively associated risk factors were AIS2-5 pelvic ring injuries (OR:2.23) and secondary deaths following an uneventful hospital discharge (OR:3.97), while AIS2-5 head (OR:0.33) and abdominal injuries (OR:0.23) showed a reverse association. CONCLUSIONS: Trauma fatalities with autopsy findings of PE were associated with less severe trauma indicating that PE was likely detrimental to the fatal outcome. Both the early and delayed occurrence of PE was reaffirmed. Prophylactic measures should be initiated promptly and extended post discharge for high risk patients to prevent secondary deaths.

Femoral fractures are an indicator of increased severity of injury for road traffic collision victims: an autopsy-based case-control study on 4895 fatalities.

INTRODUCTION: The course of road traffic collision (RTC) victims with femoral fractures (FFx) from injury to death was reviewed. We sought to correlate the presence of femoral fractures with the overall severity of injury from RTCs using objective indices and to identify statistically significant associations with injuries in other organs. PATIENTS AND METHODS: A case-control study based on forensic material from 4895 consecutive RTC-induced fatalities, between 1996 and 2005. Injuries were coded according to the Abbreviated Injury Scale-1990 Revision (AIS-90), and the Injury Severity Score (ISS) was calculated. Victims were divided according to the presence of femoral fractures in all possible anatomic locations or not. Univariate comparisons and logistic regression analysis for probabilities of association as odds ratios (OR) were performed. RESULTS: The FFx group comprised 788 (16.1%) victims. The remaining 4107 victims constituted the controls. The FFx group demonstrated higher ISS (median 48 vs 36, p < 0.001) and shorter post-injury survival times (median 60 vs 85 min, p < 0.001). Presence of bilateral fractures (15.5%) potentiated this effect (median ISS 50 vs 43, p = 0.006; median survival time 40 vs 65, p = 0.0025; compared to unilateral fractures). Statistically significant associations of FFx were identified with AIS2-5 thoracic trauma (OR 1.43), AIS2-5 abdominal visceral injuries (OR 1.89), AIS1-3 skeletal injuries of the upper (OR 2.7) and lower limbs (OR 3.99) and AIS2-5 of the pelvis (OR 2.75) (p < 0.001). In the FFx group, 218 (27.7%) victims survived past the emergency department and 116 (53.2%) underwent at least one surgical procedure. Complications occurred in 45.4% of hospitalized victims, the most common being pneumonia (34.8%). CONCLUSION: This study has documented that femoral fractures are associated with increased severity of injury, shorter survival times and higher incidence of associated thoracic, abdominal and skeletal extremity injuries, compared to controls. These findings should be considered for an evidence-based upgrading of trauma care.

A comparative autopsy study of the injury distribution and severity between suicidal and accidental high falls.

Falls are the second cause of accidental deaths worldwide. Falls from height are also a common method of suicide. The aim of this study is to compare the characteristics of the victims, the circumstances of the fall and the severity and distribution of the injuries reported in an autopsy case series of falls from height. This study is a retrospective analysis of consecutive autopsy cases of suicidal and accidental falls from height which were investigated in the Department of Forensic Medicine and Toxicology of the National and Kapodistrian University of Athens during the period 2011-2019. The recorded variables included demographic data of the victim, height of fall, length of hospital stay, toxicological results, the existence and location of injuries and Injury Severity Score (ISS). Victims of suicidal falls were younger (55.53 vs. 62.98, p = 0.001), they fell from higher heights (12.35 vs. 5.18 m, p < 0.001), and they sustained more severe injuries compared with victims of accidental falls (ISS 51.01 vs. 40.88, p < 0.001). Injuries in the thorax, abdomen, pelvis, upper and lower extremities were more frequently observed after a suicidal fall (93.6% vs. 67.3%, 72.1% vs. 21.4%, 72.1% vs. 27.6%, 42.9% vs. 15.3%, 45.7% vs. 13.3%, respectively-p < 0.001), probably due to the higher height of fall. Our study outlines the differences in the profile of the victims and in the severity of injuries caused by falls from height depending on the intention of the victim to fall. However, a distinctive injury pattern in victims of suicidal falls was not demonstrated.

Heat shock protein beta 3 (HSPB3) is an unfavorable molecular biomarker in colorectal adenocarcinoma.

Small heat shock proteins (sHSPs) participate in numerous cellular functions including cell signaling, differentiation, and apoptosis. Deregulation of the physiological expression level of sHSPs has been associated with several malignancies. Heat shock protein beta 3 (HSPB3) is the third member of the sHSP family in human and is mainly expressed in skeletal and smooth muscles. In this study, we investigated the potential prognostic significance of HSPB3 expression in colorectal adenocarcinoma, the most frequent type of colorectal cancer. For this purpose, we isolated total RNA from 188 colorectal adenocarcinoma specimens and 68 paired noncancerous ones. After reverse transcription of 2 µg total RNA, we quantified HSPB3 levels by using an in-house-developed real-time quantitative polymerase chain reaction method, based on the SYBR Green chemistry. Comparison of HSPB3 levels among 68 pairs of colorectal tumors and their adjacent noncancerous mucosae uncovered the downregulation of HSPB3 expression in the majority of malignant colorectal tumors. More importantly, high HSPB3 expression is associated with poor relapse-free survival (RFS) and overall survival (OS) of patients with colorectal adenocarcinoma. Multivariable Cox regression analysis revealed that HSPB3 overexpression could serve as an adverse prognostic biomarker in colorectal adenocarcinoma, independent of tumor location, histological grade, and TNM stage. Patients' stratification according to tumor location, histological grade, and TNM stage revealed that high HSPB3 messenger RNA expression retains its unfavorable prognostic potential regarding OS, in particular groups of patients with substantially different prognosis. In conclusion, high HSPB3 expression is associated with poor RFS and OS of patients with colorectal adenocarcioma, independently of clinicopathological prognosticators.

Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece.

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal-recessive disorder, characterized by severe osteoporosis and early-onset blindness. Loss of function mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5) have been established as the genetic defect of the disease. We report the clinical and genetic evaluation of ten OPPG cases in eight related nuclear families and their close relatives. Bone mineral density (BMD) in OPPG patients was assessed by dual-energy X-ray absorptiometry (DXA). Genotyping of LRP5 gene and targeted detection of index mutation were performed by DNA direct sequencing. Four patients were introduced to bisphosphonates. Mutational screening of LRP5 gene revealed the c.2409_2503+79del deletion in homozygous state, expected to result in a truncated protein. Among 44 members of the pedigree, 10 (22%) were identified homozygous and 34 (59%) heterozygous for this mutation. All patients had congenital blindness and 7 of them had also impaired bone mineral density. Four of them received bisphosphonates and responded with decreased bone pain and improvement in BMD; however, 3 patients presented with one fracture during treatment.Conclusion: The current study presents the molecular and clinical profiles of 10 new OPPG cases, being part of an extended pedigree. Patients who received bisphosphonate treatment responded well with increase in their BMD, though fractures occurred during therapy. What is known: • OPPG syndrome is a rare genetic disorder characterized by congenital blindness and juvenile osteoporosis. • Loss of function mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5) is the genetic defect of the disease. What is new: • Genetic and clinical phenotype of 10 new OPPG patients. • The ten new OPPG patients presented with phenotypical variability in osseous manifestations.

High microRNA-28-5p expression in colorectal adenocarcinoma predicts short-term relapse of node-negative patients and poor overall survival of patients with non-metastatic disease.

BACKGROUND: MicroRNAs (miRNAs) may function either as oncogenes or tumor suppressors and are heavily involved in the initiation and progression of cancer, and in metastasis of tumor cells. MicroRNA-28-5p (miR-28-5p) targets several cancer-related genes and is hence involved in cell proliferation, migration, invasion and epithelial-mesenchymal transition. In this study, we investigated the potential diagnostic and prognostic significance of miR-28-5p expression in colorectal adenocarcinoma, the most frequent type of colorectal cancer (CRC). METHODS: Therefore, we isolated total RNA from 182 colorectal adenocarcinoma specimens and 86 paired non-cancerous colorectal mucosae. After polyadenylation of 2 µg total RNA and its reverse transcription using an oligo-dT-adapter primer, we quantified miR-28-5p levels using an in-house-developed reverse-transcription real-time quantitative polymerase chain reaction (RT-qPCR) method, based on the SYBR Green chemistry. RESULTS: Comparison of miR-28-5p levels among 86 pairs of colorectal tumors and their adjacent non-cancerous mucosae uncovered the downregulation of miR-28-5p expression in the majority of malignant colorectal tumors. More importantly, high miR-28-5p expression predicts poor disease-free survival (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Multivariate Cox regression analysis revealed that miR-28-5p overexpression is a significant predictor of poor prognosis in colorectal adenocarcinoma, independent of tumor size, histological grade, TNM staging, radiotherapy and chemotherapy. Interestingly, strong miR-28-5p expression retains its predictive potential regarding relapse among patients with negative regional lymph nodes, and predicts poor OS in patients diagnosed with non-metastatic colorectal adenocarcinoma. CONCLUSIONS: High miR-28-5p expression predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological prognosticators and standard patient treatment, including radiotherapy and chemotherapy.

Upregulated miR-16 expression is an independent indicator of relapse and poor overall survival of colorectal adenocarcinoma patients.

BACKGROUND: Colorectal adenocarcinoma is one of the most common malignant tumors of the gastrointestinal tract and the second leading cause of cancer-related deaths among adults in Western countries. miR-16 is heavily involved in cancer progression. In this study, we examined the potential diagnostic and prognostic utility of miR-16 expression in colorectal adenocarcinoma. METHODS: Total RNA was extracted from 182 colorectal adenocarcinoma specimens and 86 non-cancerous colorectal mucosae. After polyadenylation of 2 µg total RNA by poly(A) polymerase and subsequent reverse transcription with an oligo-dT adapter primer, miR-16 expression was determined using an in-house developed reverse transcription quantitative real-time PCR method, based on SYBR Green chemistry. SNORD43 (RNU43) and SNORD48 (RNU48) were used as reference genes. Next, we performed extensive biostatistical analysis. RESULTS: miR-16 was shown to be significantly upregulated in colorectal adenocarcinoma specimens compared to non-cancerous colorectal mucosae, suggesting its potential exploitation for diagnostic purposes. Moreover, high miR-16 expression predicts poor disease-free survival (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Multivariate Cox regression analysis confirmed that miR-16 overexpression is a significant unfavorable prognosticator in colorectal adenocarcinoma, independent of other established prognostic factors, radiotherapy, and chemotherapy. Interestingly, miR-16 overexpression retains its unfavorable prognostic value in patients with advanced yet locally restricted colorectal adenocarcinoma that has not grown through the wall of the colon or rectum (T3) and in those without distant metastasis (M0). CONCLUSIONS: Overexpression of the cancer-associated miR-16 predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological factors that are currently used for prognostic purposes.

High miR-96 levels in colorectal adenocarcinoma predict poor prognosis, particularly in patients without distant metastasis at the time of initial diagnosis.

MicroRNA-96 (miR-96) is an oncomiR that facilitates the development of malignant tumors by promoting growth, proliferation, and survival of cancer cells. Previous studies using high-throughput techniques have shown that miR-96 is upregulated in colorectal cancer compared to adjacent normal colorectal tissue. The aim of this study was the investigation of the potential clinical value of miR-96 as a molecular prognostic biomarker in colorectal adenocarcinoma. For this purpose, total RNA was extracted from 108 primary colorectal adenocarcinoma samples and 54 paired non-cancerous colorectal tissue specimens. After polyadenylation and reverse transcription, miR-96 molecules were determined using an in-house developed real-time quantitative PCR based on SYBR Green chemistry. Calculations were carried out with the comparative CT method, using SNORD48 as endogenous reference gene. Finally, extensive biostatistical analysis was performed and showed that miR-96 is significantly upregulated in colorectal adenocarcinoma specimens compared to their non-cancerous counterparts (p < 0.001) as well as in tumors having invaded regional lymph nodes (p = 0.009) and those of advanced TNM stage (p = 0.008). miR-96 expression is an unfavorable prognostic marker in colorectal adenocarcinoma, predicting poor disease-free and overall survival (p = 0.041 and 0.028, respectively), independently of classical clinicopathological parameters. Most importantly, miR-96 expression stratifies patients without distant metastasis (M0) at the time of diagnosis into two groups with substantially different prognosis (p = 0.040). In conclusion, high tissue levels of miR-96 are associated with advanced stages of colorectal adenocarcinoma and predict an increased risk for disease recurrence and poor overall survival, especially in patients without distant metastasis at the time of diagnosis.

Kallikrein-related peptidase-6 (KLK6) mRNA expression is an independent prognostic tissue biomarker of poor disease-free and overall survival in colorectal adenocarcinoma.

Members of the family of tissue kallikrein and kallikrein-related peptidases possess important prognostic value in cancer. Moreover, the oncogenic role of kallikrein-related peptidase-6 (KLK6) in colorectal cancer has been well documented so far. This study investigated the prognostic value of KLK6 mRNA expression as a molecular tissue biomarker in colorectal adenocarcinoma. For this purpose, KLK6 mRNA expression was studied in 110 primary colorectal adenocarcinomas and 39 paired noncancerous colorectal specimens. A dramatic upregulation of KLK6 mRNA expression was observed in colorectal tumors. KLK6 mRNA overexpression was associated with high depth of tumor invasion, presence of distant metastases, and tumor-node-metastasis (TNM) stage of patients. Furthermore, KLK6 mRNA expression was shown to predict poor disease-free and overall survival independently of patient gender, age, tumor size, location, histological subtype, grade, venous invasion, lymphatic invasion, TNM stage, radiotherapy, and chemotherapy treatment. Moreover, Kaplan-Meier survival analysis revealed that colorectal adenocarcinoma patients with negative regional lymph nodes (N0) and those without distant metastases (M0) harboring KLK6 mRNA-positive colorectal tumors tended to relapse and die earlier than N0 and M0 patients with KLK6 mRNA-negative colorectal adenocarcinoma. Thus, KLK6 mRNA expression could be considered as an independent, unfavorable molecular prognostic biomarker in colorectal adenocarcinoma, with additional prognostic value in patients without regional or distant metastases.

Enhanced miR-182 transcription is a predictor of poor overall survival in colorectal adenocarcinoma patients.

BACKGROUND: Colorectal cancer is the second most frequent cause of cancer-related death in the developed world. Recent studies have tried to associate colorectal cancer with the aberrant expression of several microRNAs. The aim of the present study was the development of a highly sensitive quantitative real-time PCR which can be used to evaluate the miR-182 expression levels in colorectal adenocarcinoma and adjacent non-cancerous tissue specimens and associate them with several clinicopathological characteristics, aiming to examine the prognostic potential of miR-182. METHODS: Total RNA was isolated from 116 malignant colorectal adenocarcinoma specimens and 60 paired non-cancerous tissues. Then, polyadenylation of 2 µg total RNA by poly(A) polymerase and reverse transcription with suitable oligo-dT-adapter followed. miR-182 levels were quantified by real-time PCR based on SYBR Green chemistry. The results were analyzed by the comparative quantification cycle method and by extensive biostatistical analysis. RESULTS: miR-182 was found to be significantly upregulated in colorectal adenocarcinoma specimens compared to their non-cancerous counterparts (p<0.001). miR-182 expression increases as the histological grade increases (p=0.013). miR-182 overexpression is associated with high depth of tumor invasion, positive regional lymph node status, and advanced TNM stage of patients. Therefore, miR-182 is an unfavorable prognostic marker in colorectal adenocarcinoma, predicting poor overall survival (p=0.007). Most importantly, miR-182 expression retained its unfavorable prognostic significance among patients with well- or moderately differentiated colorectal adenocarcinoma (p=0.006) and among metastasis-free patients (p=0.025). CONCLUSIONS: The increased levels of the oncogene-like miR-182 increase the risk for disease progression and predict poor overall survival for colorectal adenocarcinoma patients.

The long-term need for calcium supplementation after incidental parathyroidectomy.

Objectives: Hypocalcaemia and hypoparathyroidism are the most frequent complications of total thyroidectomy that may result in the need for lifelong calcium supplementation. This study aims to investigate the impact of incidental parathyroidectomy on short- and long-term hypocalcaemia. Methods: This retrospective study was conducted on patients who underwent total thyroidectomy with or without central neck dissection between March 2016 to May 2018. All procedures were performed by three surgeons with similar experience levels. Histopathology reports were reviewed, the number of resected parathyroid glands and the underlying pathology reports were recorded, and the patients were divided into two groups; groups A and B comprised those with and without parathyroid glands respectively. The incidence rates of short- and long-term hypocalcaemia were recorded. The former was obtained through blood tests during hospitalisation and the latter via phone calls to patients 3, 6, and 12 months postoperatively. Results: A total of 116 patients participated, 18 (15.5%) in group A and 98 (84.5%) in group B. No statistical significance was detected between the two groups regarding early postoperative (p = 0.109) or long-term hypocalcaemia (p = 0.48). These results were similar in patients with cancer (n = 40) (p = 0.855, p = 0.08). Conclusion: Incidental parathyroidectomy of one parathyroid gland was not correlated with a higher incidence of hypocalcaemia, even in cases with thyroid cancer.

High Expression of a tRNAPro Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence.

Colorectal cancer (CRC) is the second most lethal cause of cancer-related deaths in Europe. Fragments of tRNAPro are conserved among vertebrates, characterized by pleiotropic regulatory functions and have been found to discriminate colorectal tumors from normal colorectal mucosa. In the current study, we investigated the prognostic utility of 5'-tiRNA-ProTGG levels in CRC. For this purpose, total RNA was extracted from 155 malignant colorectal tumors and 74 adjacent non-cancerous tissue specimens, polyadenylated and reverse-transcribed using an oligo-dT adapter as primer. Real-time quantitative PCR (qPCR) was used to assess the levels of 5'-tiRNA-ProTGG. Kaplan-Meier survival analysis demonstrated that high 5'-tiRNA-ProTGG levels predict both poor disease-free survival (DFS) and overall survival (OS) of CRC patients. Of note, high 5'-tiRNA-ProTGG levels retain their unfavorable prognostic value in patients with rectal cancer and/or moderately differentiated CRC (grade II). More importantly, multivariate cox regression analysis highlighted that the overexpression of 5'-tiRNA-ProTGG constitutes an adverse prognostic factor predicting short-term relapse of CRC patients independently of the established prognosticators in CRC. Finally, bioinformatics analysis unveiled a potentially critical role of 5'-tiRNA-ProTGG regarding the maintenance of cellular homeostasis, signaling, cell communication, and cellular motility.

Effect of Crocus sativus (Saffron) Intake on Top of Standard Treatment, on Disease Outcomes and Comorbidities in Patients with Rheumatic Diseases: Synthesis without Meta-Analysis (SWiM) and Level of Adherence to the CONSORT Statement for Randomized Controlled Trials Delivering Herbal Medicine Interventions.

Rheumatic diseases (RDs) are often complicated by chronic symptoms and frequent side-effects associated with their treatment. Saffron, a spice derived from the Crocus sativus L. flower, is a popular complementary and alternative medicine among patients with RDs. The present systematic review aimed to summarize the available evidence regarding the efficacy of supplementation with saffron on disease outcomes and comorbidities in patients with RD diagnoses. PubMed, CENTRAL, clinicaltrials.gov and the grey literature were searched until October 2021, and relevant randomized controlled trials (RCTs) were screened for eligibility using Rayyan. Risk of bias was assessed using the Cochrane's Risk of Bias-2.0 (RoB) tool. A synthesis without meta-analysis (SWiM) was performed by vote counting and an effect direction plot was created. Out of 125 reports, seven fulfilled the eligibility criteria belonging to five RCTs and were included in the SWiM. The RCTs involved patients with rheumatoid arthritis, osteoarthritis and fibromyalgia, and evaluated outcomes related to pain, disease activity, depression, immune response, inflammation, oxidative stress, health, fatigue and functional ability. The majority of trials demonstrated some concerns regarding overall bias. Moreover, the majority of trialists failed to adhere to the formula elaborations suggested by the CONSORT statement for RCTs incorporating herbal medicine interventions. Standardization of herbal medicine confirms its identity, purity and quality; however, the majority of trials failed to adhere to these guidelines. Due to the great heterogeneity and the lack of important information regarding the standardization and content of herbal interventions, it appears that the evidence is not enough to secure a direction of effect for any of the examined outcomes.

Molecular analysis and prognostic impact of the novel apoptotic gene BCL2L12 in gastric cancer.

Stomach cancer comprises a malignancy with feeble prognosis. In gastric carcinogenesis, molecular alterations in the apoptosis-related genes have been described. In this study, the expression of BCL2-like-12 (BCL2L12) gene, discovered and cloned by members of our group, was investigated in a statistically significant sample size of cancerous and non-cancerous stomach tissues and gastric cancer cells with quantitative real-time PCR methodology. BCL2L12 transcript was indicated in cancer gastric tissues to range from 29 to 53200 mRNA copies BCL2L12/10(6) mRNA copies GAPDH. Significant associations of BCL2L12 with gastric tumors of the early stages (I/II) (p=0.044) and of intestinal histotype (p=0.034) was substantiated. Both univariate and multivariate analyses disclosed, respectively, BCL2L12 relationship with disease-free (p=0.006 and p=0.025) and overall patients' survival (p=0.007 and p=0.022). Our results open new horizons for the possible application of BCL2L12 as a novel prognostic indicator of gastric cancer.

Comparative Study of Dermatological Diseases of the Elderly in Relation to the Rest Population.

BACKGROUND: According to Eurostat, the geriatric population in Greece constitutes almost 21.8% of the total population, with an increasing tendency. Skin diseases of the elderly often originate from internal medicine diseases. The aim of this study was to identify different dermatological conditions among patients over 65 years of age compared to younger patients. METHODS: The present study was conducted between May 2015 and December 2017 in public medical offices in the Municipality of Thessaloniki. A total of 8422 patients of all ages were screened and their dermatological problem was recorded. The sample was then divided into two age groups. The first group was composed of 3629 elderly patients over 65 years of age. The second group consisted of 4793 patients up to 65 years old. RESULTS: Pruritus was the main dermatological complaint in the elderly (14.2%) compared to the younger age group (1%), who were more interested in their mole examination (15.1%). Precancerous lesions (4%) and skin cancers (2.4%) presented more frequently in elderly patients than in people younger than 65 years old (0.7% and 0.5%, respectively). CONCLUSION: There are significant differences in the frequency and etiology of dermatological diseases between the two age groups. Pruritus and non-cancerous tumors of the elderly are considered to be the main findings of geriatric dermatology.

Unique Skin Metastasis from Recurrent Cancer. Case Report.

INTRODUCTION: Cutaneous metastasis is defined as the dissemination of malignant cells from a primary tumor to the skin. Skin may be affected by tumors, either through direct invasion from an adjacent organ or by cutaneous metastasis from an internal organ malignancy. We report a case of a 75-year-old female patient with skin metastasis 8 years after the initial treatment of primary breast cancer. PATIENT CONCERN: The patient presented only with papules and nodular skin lesions in the left lateral abdominal area, without any other clinical manifestations. DIAGNOSIS: All laboratory tests were normal. Histological examinati revealed the infiltration of the dermis by tumor cells. INTERVENTIONS/OUTCOME: After the diagnosis of skin metastasis, she was treated with chemotherapy with complete remission of skin lesions. CONCLUSION: Skin metastasis from internal organs is rarely the first sign. In this case, skin metastasis was the only clinical sign and the only diagnostic tool to drive to the correct diagnosis of a recurrent cancer after 8 years. Dermatologists might be the first doctors to facilitate the diagnosis of skin metastasis.

High clusterin (CLU) mRNA expression levels in tumors of colorectal cancer patients predict a poor prognostic outcome.

OBJECTIVES: Clusterin (CLU) is a multifunctional intra-/extra-cellular molecular chaperone with indications of serving as a promising prognostic biomarker for colorectal cancer (CRC). Several studies have examined the potential prognostic value of the CLU protein in CRC; however, our research follows an alternative approach, focusing on the CLU mRNA expression. DESIGN AND METHODS: Total RNA from 172 cancerous tissue specimens and 39 paired non-cancerous ones was isolated and 2 µg of this were subjected to reverse transcription with an oligo-dT primer. The single stranded DNA, which was synthesized, was amplified with an in-house developed highly sensitive and precise qPCR method, using specific pair of primers for the CLU molecule. Finally, an extensive biostatistical analysis took place for the assessment of the results. RESULTS: Patients with tumors expressing high CLU mRNA levels had a higher probability for poor outcome (relapse and death), comparing to those with CLU mRNA-negative tumors. This association between CLU mRNA expression status and both disease-free survival (DFS) and overall survival (OS) is evident in Cox regression analysis and is also depicted in the Kaplan-Meier survival curves. Consistently, the aforementioned associations and the CLU mRNA expression levels are significantly enhanced as CRC tumors progress from TNM stage I to IV, further supporting the functional implication of CLU in tumorigenesis. CONCLUSIONS: High CLU mRNA levels in CRC tumors can act as a new adverse prognostic biomarker of DFS and OS for CRC, independent of clinicopathological and biological features of the patient.

TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer.

BACKGROUND: Patients with stage II-III colorectal cancer (CRC) treated with adjuvant chemotherapy, gain a 25% survival benefit. In the context of personalized medicine, there is a need to identify patients with CRC who may benefit from adjuvant chemotherapy. Molecular profiling could guide treatment decisions in these patients. Thymidylate synthase (TYMS) gene polymorphisms, KRAS and BRAF could be included in the molecular profile under consideration. AIM: To investigate the association of TYMS gene polymorphisms, KRAS and BRAF mutations with survival of CRC patients treated with chemotherapy. METHODS: A retrospective study studied formalin-fixed paraffin-embedded tissues (FFPEs) of consecutive patients treated with adjuvant chemotherapy during January/2005-January/2007. FFPEs were analysed with PCR for the detection of TYMS polymorphisms, mutated KRAS (mKRAS) and BRAF (mBRAF). Patients were classified into three groups (high, medium and low risk) according to 5'UTR TYMS polymorphisms Similarly, based on 3'UTR polymorphism ins/loss of heterozygosity (LOH) patients were allocated into two groups (high and low risk of relapse, respectively). Cox regression models examined the associated 5-year survival outcomes. RESULTS: One hundred and thirty patients with early stage CRC (stage I-II: 55 patients; stage III 75 patients; colon: 70 patients; rectal: 60 patients) were treated with surgery and chemotherapy. The 5-year disease free survival and overall survival rate was 61.6% and 73.9% respectively. 5'UTR polymorphisms of intermediate TYMS polymorphisms (2RG/3RG, 2RG/LOH, 3RC/LOH) were associated with lower risk for relapse [hazard ratio (HR) 0.320, P = 0.02 and HR 0.343, P = 0.013 respectively] and death (HR 0.368, P = 0.031 and HR 0.394, P = 0.029 respectively). The 3'UTR polymorphism ins/LOH was independently associated with increased risk for disease recurrence (P = 0.001) and death (P = 0.005). mBRAF (3.8% of patients) was associated with increased risk of death (HR 4.500, P = 0.022) whereas mKRAS (39% of patients) not. CONCLUSION: Prospective validating studies are required to confirm whether 2RG/3RG, 2RG/LOH, 3RC/LOH, absence of ins/LOH and wild type BRAF may indicate patients at lower risk of relapse following adjuvant chemotherapy.

Status and perspectives of hospital mortality in a public urban Hellenic hospital, based on a five-year review.

BACKGROUND: Analysis of hospital mortality helps to assess the standards of health-care delivery. METHODS: This is a retrospective cohort study evaluating the causes of deaths which occurred during the years 1995-1999 in a single hospital. The causes of death were classified according to the International Statistical Classification of Diseases (ICD-10). RESULTS: Of the 149,896 patients who were discharged the 5836 (3.4%) died. Males constituted 55% and females 45%. The median age was 75.1 years (1 day - 100 years). The seven most common ICD-10 chapters IX, II, IV, XI, XX, X, XIV included 92% of the total 5836 deaths. The most common contributors of non-neoplasmatic causes of death were cerebrovascular diseases (I60-I69) at 15.8%, ischemic heart disease (I20-I25) at 10.3%, cardiac failure (I50.0-I50.9) at 7.9%, diseases of the digestive system (K00-K93) at 6.7%, diabetes mellitus (E10-E14) at 6.6%, external causes of morbidity and mortality (V01-Y98) at 6.2%, renal failure (N17-N19) at 4.5%, influenza and pneumonia (J10-J18) at 4.1% and certain infectious and parasitic diseases (A00-B99) at 3.2%, accounting for 65.3% of the total 5836 deaths. Neoplasms (C00-D48) caused 17.7% (n = 1027) of the total 5836 deaths, with leading forms being the malignant neoplasms of bronchus and lung (C34) at 3.5% and the malignant neoplasms of large intestine (C18-21.2) at 1.5%. The highest death rates occurred in the intensive care unit (23.3%), general medicine (10.7%), cardiology (6.5%) and nephrology (5.5%). Key problems related to certification of death were identified. Nearly half of the deaths (49.3%: n = 2879) occurred by the completion of the third day, which indicates the time limits for investigation and treatment. On the other hand, 6% (n = 356) died between the 29th and 262nd days after admission. Inadequacies of the emergency care service, infection control, medical oncology, rehabilitation, chronic and terminal care facilities, as well as lack of regional targets for reducing mortality related to diabetes, recruitment of organ donors, provision for the aging population and lack of prevention programs were substantiated. CONCLUSION: Several important issues were raised. Disease specific characteristics, as well as functional and infrastructural inadequacies were identified and provided evidence for defining priorities and strategies for improving the standards of care. Effective transformation can promise better prospects.

Dislodged biliary stent causes lower gastrointestinal hemorrhage four years postendoscopic retrograde cholangiopancreatography.

Endoscopic biliary stent placement is an efficient method for the decompression of the biliary system in various benign and malignant causes. Dislocation and stent migration is a well-known complication, with most displaced stents passing through the bowel, uneventfully. Rarely, migrated stents can be accounted for potentially life-threatening complications.