Death by artery injury: two peculiar cases of sharp force fatality.

Background: As sharp force injury accounts for 10-20% of clinical forensic examinations, forensic pathologists are often asked to investigate deceased victims of stab wounds. Moreover, homicide by sharp force (stabbing) is one of the most common in European countries, involving generally domestic or interpersonal conflict. Stabbing as a suicide method constitutes a low percentage of all suicides, 2% to 3%. Accidental death due to sharp force is even rarer (0-3%) and usu-ally caused by an impact or a fall into different type of glass surface. Death due to stabbing is usually caused by exsanguinating incisions to organs or large blood vessels (such as arteries), leading to haemor-rhagic shock. Penetrating artery injuries are well known in clinical settings, and extremities are the most common sites of such injuries. Indeed, 50% to 60% of injuries occur in femoral or popliteal arteries, 30% in brachial artery. Aims: The aim of this paper is to present two rare cases of sharp force fatality, showing how a thorough forensic pathology methodology, including death scene investigation, autopsy examination, and toxicological analyses, are pivotal to detect the manner of death. Case Reports: This paper presents two peculiar cases of sharp force fatalities: the first, a single and accidental stab injury on the right armpit which caused a complete transection of the axillary artery; the second, a single homicidal stab wound on the lower leg causing a full-thickness lesion of the anterior tibial artery.

Vitamin D status of inmates: the experience of penitentiaries prisons in the province of Salerno in Southern Italy.

Introduction: Prisoners are at risk of developing vitamin D deficiency due to their lacking exposure to sunlight. So far, there are no published studies evaluating blood levels of vitamin D in relation to the health status of inmates and the quality of the Italian prison system. Aim: To investigate vitamin D status and its determinants in a cohort of prisoners. Subject and Methods: One hundred and seventy-two (172) pri-son inmates (males, n=159, age 47± 11.3 years; females, n=13, age 43.91±12.18 years) of three penitentiaries in the province of Salerno. Vitamin D deficiency, insufficiency and sufficiency were respectively defined as a 25(OH)D level <20 ng/mL; from 20 to 30 ng/mL, >30 ng/mL. Results: In our group, Vitamin D deficiency occurs in 77.32% of the prisoners with 32.55% of the cases having severe insufficiency. Prisoners with higher BMI show lower circulating vitamin D levels (p<0.001). No significant relationship was found with the duration of detention (Pearson R: 0.01). Conclusion: In this cohort of inmates the vitamin D status is determined by BMI, but not by the duration of the detention.

Abuse and misuse of prescription opioids: is it only an Ameri- can problem? An observational study on an Italian casuistry.

ABSTRACT: Medical use of prescription opioids has steadily increased since the 1990s, particularly in the U.S.A. and Canada, along with abuse of these substances and significant increases in rates of addiction and death related to prescription opioids. The American authorities speak of an "addiction epidemic" and are launching a series of countermeasures to better address the problem. In Europe, there is an increasing use of prescription opioids and related problems, but the European context is much less dramatic than the American and Canadian ones. Never-theless, based on the data, it cannot be ruled out that a similar crisis will occur on the Old Continent. The aim of this study is to analyze the Italian context to better understand whether there is a possibility of an addiction epidemic. Twenty-four cases of death of people under treatment with pre-scription opioids have been retrospectively analyzed. Toxicological samples were collected with routine methods during the autopsy, followed by systematic screening for substances by diverse methods. Volatile compounds were identified using gas chromatography-flame ionization detection (GC-FID). Medical drugs and drugs of abuse were identified via the use of gas chromatography-mass spectrome-try (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS). Of a total of 24 subjects, 14 died due to an overdose of Tramadol, while 7 died due to an overdose of Buprenorphine and 3 dues to a Fentanyl overdose. The most used drug was Tramadol. Histological examination was performed with hematoxylin/eosin staining, though no significant findings emerged apart from widespread edema and focal sclerosis of the myocardium, and interstitial and alveolar edema of the lungs. Our data show that attention must be paid to prescription opioids. European institutions, as soon as possible, must implement preventive measures that avoid the recurrence of the North American situation.

Comparative study between conventional and new methods in defining the cause of death from anaphylactic shock.

ABSTRACT: Anaphylaxis is defined as a rapid systemic reaction that develops in individuals previously exposed to specific allergens. The new exposure causes systemic cellular degranulation, which in turn leads to cardiovascular and respiratory changes that are fatal if not treated immediately. One of the main problems of this scenario in the forensic field is the determination of a correct post-mortem diagnosis. Traditional methods, such as histopathological examination of the respiratory tract and the use of specific antibodies used in immunohistochemistry, are sensitive but not always specific and therefore do not guarantee a high degree of probability in the diagnosis of anaphylaxis. For this reason, a new and promising research frontier in this field of forensic pathology could be represented by the application of miRNAs as biomarkers, as has been done in other areas of medicine.

Estimation of the time of death: where we are now?

ABSTRACT: One of the increasingly discussed topics in forensic pathology is that concerning the quantification of the postmortem interval (PMI). The estimation of the time interval between the death of a person and the discovery of the body is extremely complicated, as it is affected by the influence of many factors, both endogenous and exogenous. With the advancement of knowledge in the field of molecular biology, several studies have been performed, for more than 30 years, on the degradation pattern of macromolecules, such as proteins, DNA, RNA, and the relationship with PMI. Despite initial enthusiasm, studies have shown different kind of limitations in determining PMI in the forensic field. In the last years, consequently, researchers focused their attention on the potential of microRNAs as housekeeping genes, due to their postmortem stability and resistance to degradation. MiRNAs are small, endogenous, single stranded, non-coding RNA molecules identified in plants, animals and DNA virus transcriptome. Various and growing are the fields of application: to establish time of death, to evaluate vitality of skin lesions, in cases of head trauma, and cases of acute myocardial infarction. Their use could also be particularly useful in determining late PMI (beyond 24 hours after death), as no additional markers are available in this scenario. At the moment, scientific research is still at an early stage as it is mainly based on animal models. However, the promising properties of miRNAs and their low cost may make this field of research very interesting for an increasingly precise determination of PMI in the future.

Crossbow injuries: A case report with experimental reconstruction study and a systematic review of literature.

In modern times crossbow - a ranged weapon diffused during Middle Ages - is increasing its popularity in recreational hunting and sports; crossbow bolts have a great penetration capacity, despite their low initial velocity. Great concerns emerge when considering that notwithstanding crossbow is a potentially lethal distance weapon, it is easy to obtain without having to undertake any tests on the buyer's mental or physical health. Although rare, crossbow injuries can be challenging for the forensic pathologist due to great similarities with other wounds pattern (gunshots wounds or injury due to sharp force). Especially when the arrow is removed from its original position or the body is decomposed, identification of the weapon can be difficult. According to forensic literature, suicides, homicides and non-lethal injuries by crossbow have been reported up to the present day. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) indications in the identification and selection of studies and reviewed a series of cases of both fatal and non-fatal crossbow injuries, according to the manner of death (homicide, suicide, accidental). The casuistic part of this paper deals with an attempted murder of a 21-year old man: a case of non-lethal crossbow injury of the thorax in which an interdisciplinary approach, involving forensic inspection, ballistic and radiology tests, led to solve the case.

Post-mortem diagnosis of sepsis: when it's too late.

Post-mortem diagnosis of sepsis is often very difficult to make, especially in the elderly affected by multiple comorbidities. However, clinical evaluation following histology, immunohistochemistry, microbiological tests, immunoassays and proteomics can improve reliability of this post-mortem diagnosis.

Forensic pathology: past, present and future.

Forensic pathology is the scientific branch which, more than every other, today draws from new technologies inherent to other medical fields. In the last century history of forensic pathology has been characterized by a necessary conjunction between tradition and innovation, which primary achievement is finding the truth and scientific objectivity. During the past centuries several studies have enriched scientific forensic panorama, until the most recent introductions in radiological fields (3D post-mortal CT and MRI) and in the molecular biological one, with disclosure of miRNA. MiRNAs are small, endogenous, single stranded, non-coding RNA molecules identified in plants, animals and DNA virus transcriptome. Various and growing are the fields of application: to establish time of death, to evaluate vitality of skin lesions, in cases of head trauma, and cases of acute myocardial infarction. The introduction of new molecular biology techniques will certainly be useful in the coming years to find the "truth" in challenging judicial cases.

Response to letter to the Editor regarding physical restraint in psychiatric setting.

The following letter addresses the issues of the applicability of physical restriction, with particular attention to the therapeutic regime and its meaning as a therapeutic or restrictive provision, while considering possible alternative measures in the context of Italian jurisprudence. The letter, in response to the questions posed by Cioffi and Tomassini, examines the possible legal implications for doctors and suggests that the integration of jurisprudence and psychiatry seems to be mandatory to define the operational protocols for the management of physical restraint. La seguente lettera affronta il problema relativo all'applicabilità della contenzione fisica, con particolare riferimento al regime terapeutico, nonché la sua valenza giuridica quale misura terapeutica o restrittiva, considerando eventuali approcci alternativi. La lettera, in risposta alle domande poste da Cioffi e Tomassini, esamina le possibili implicazioni legali cui possono incorrere i medici nell'applicare la contenzione fisica, suggerendo la necessità di un'integrazione tra le norme giurisprudenziale e la scienza psichiatrica, al fine di definire i protocolli operativi di gestione della contenzione fisica.

The importance of Post Mortem Computed Tomography (PMCT) in the reconstruction of the bullet trajectory.

INTRODUCTION: Post Mortem Computed Tomography (PMCT) and 3D reconstruction provide a powerful tool in the evaluation of the causes of death, distinguishing between those findings related to traumas and those related to post mortal changes. It has proven to be extremely useful in case of violent deaths as a support to the traditional autopsy. AIM OF THE STUDY: The aim of the study is to prove the essential role of PMCT in the determination of the cause of death. For this purpose, we present a case of homicide where CT scans were performed before the autopsy, thus bringing to the resolution of an otherwise controversial death. CASE PRESENTATION: A 17 years old male died from a gunshot fired by a policeman during a chase. There were some controversies in this case that brought it to the national mediatic attention. PMCT reconstructed images showed the entry point and the ballistic trajectory of the bullet, moreover, PMCT high sensitivity in the evaluation of bone lesions, made the technique diriment in the clarification of the sequence of events that brought to the death of the subject, resolving the controversies of the case. In fact, it showed that the trajectory of the bullet could have not been compatible with the victim's family thesis.

Is it time for international guidelines on physical restraint in psychiatric patients?

The freedom-restraining measures used during Involuntary Health Treatment (IHT) are highly criticized in the medical community. Physical restraint techniques are currently largely used worldwide in Psychiatry. The use of restraints against the patient's will can be considered a serious intrusion of basic human rights and even an act of violence against the patient. In all cases, the restraint should not lead to injuries or damage to the patient's health and should be implemented with a respect of the human rights and dignity. Generally, the use of restraint should be considered as a last resource, when all the other methods have failed. Since it represents the principal freedom-limitation measure, it should be constantly monitored by physicians who apply these methods. The case of a 58 years-old white male, affected by chronic schizoaffective disorder and cannabinoid dependence, was under involuntary medical treatment as a consequence of antisocial behavior. During the IHT he suffered firstly a pharmacological restraint and then a physical restraint in order to suppress a slight state of agitation. The patient was completely blocked to the bed for more than 80 hours and died after three days of hospitalization. The aim of this study is to evaluate the suitability of restrictive methods for psychiatric patients in order to establish specific rules to prevent abuse of restraint techniques and even to help physicians to treat psychiatric patients.

The association of financial difficulties with clinical outcomes in cancer patients: secondary analysis of 16 academic prospective clinical trials conducted in Italy.

BACKGROUND: Cancer may cause financial difficulties, but its impact in countries with public health systems is unknown. We evaluated the association of financial difficulties with clinical outcomes of cancer patients enrolled in academic clinical trials performed within the Italian public health system. PATIENTS AND METHODS: Data were pooled from 16 prospective multicentre trials in lung, breast or ovarian cancer, using the EORTC quality of life (QOL) C30 questionnaire. Question 28 scores financial difficulties related to disease or treatment in four categories from 'not at all' to 'very much'. We defined financial burden (FB) as any financial difficulty reported at baseline questionnaire, and financial toxicity (FT) as score worsening in a subsequent questionnaire. We investigated (i) the association of FB with clinical outcomes (survival, global QOL response [questions 29/30] and severe toxicity), and (ii) the association of FT with survival. Multivariable analyses were performed using logistic regression models or the Cox model adjusting for trial, gender, age, region and period of enrolment, baseline global QOL and, where appropriate, FB and global QOL response. Results are reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI). RESULTS: At baseline 26% of the 3670 study patients reported FB, significantly correlated with worse baseline global QOL. FB was not associated with risks of death (HR 0.94, 95% CI 0.85-1.04, P = 0.23) and severe toxicity (OR 0.90, 95% CI 0.76-1.06, P = 0.19) but was predictive of a higher chance of worse global QOL response (OR 1.35, 95% CI 1.08-1.70, P = 0.009). During treatment, 2735 (74.5%) patients filled in subsequent questionnaires and 616 (22.5%) developed FT that was significantly associated with an increased risk of death (HR 1.20, 95% CI 1.05-1.37, P = 0.007). Several sensitivity analyses confirmed these findings. CONCLUSION: Even in a public health system, financial difficulties are associated with relevant cancer patients outcomes like QOL and survival. CLINICAL TRIALS NUMBER: Any registered clinical trial number should be indicated after the abstract.

Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial.

BACKGROUND: Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. PATIENTS AND METHODS: We carried out a multicenter, randomized phase III study. Women aged 65-79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m(2) days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. RESULTS: From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83-1.76, P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80-2.22, P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. CONCLUSIONS: Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. CLINICALTRIALSGOV: NCT00331097.

The Breast Avastin Trial: phase II study of bevacizumab maintenance therapy after induction chemotherapy with docetaxel and capecitabine for the first-line treatment of patients with locally recurrent or metastatic breast cancer.

BACKGROUND: Therapeutic approach for patients with metastatic breast cancer (MBC) is still controversial. This study was conducted to assess the efficacy and safety of bevacizumab in combination with docetaxel plus capecitabine as first-line treatment for MBC. The feasibility of bevacizumab maintenance therapy in this setting was also evaluated. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients received bevacizumab 15 mg/kg and docetaxel 60 mg/m(2) on day 1, plus capecitabine 900 mg/m(2) twice daily on days 1-14 every 21 days. Treatment was administered for up to 6 cycles, then bevacizumab continued until progressive disease. The primary end point was progression-free survival (PFS); secondary end points were tumor response rate, overall survival, and toxicity. RESULTS: Seventy-nine eligible patients were treated with bevacizumab in combination with docetaxel plus capecitabine. The overall response rate was 61 %, with a complete response rate of 8 % and a median duration of response of 10 months. At a median follow-up of 28 months, the median PFS was 11 months. Fifty-two (65 %) patients received bevacizumab maintenance therapy for a median duration of 7 months (range 1 to 33+). Neutropenia was the most common grade 3-4 toxicity (28.1 % of patients), and two fatal adverse events occurred (septic shock and gastrointestinal perforation). CONCLUSIONS: Bevacizumab in combination with docetaxel and capecitabine demonstrates significant activity and quite acceptable toxicity profile as first-line treatment of MBC. Subsequent maintenance therapy with bevacizumab is feasible for a long period of stable disease. Results deserve confirmation.

Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

BACKGROUND: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. PATIENTS AND METHODS: A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. RESULTS: Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). CONCLUSIONS: In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

Biological characteristics and medical treatment of breast cancer in young women-a featured population: results from the NORA study.

BACKGROUND: The present paper described the biological characteristics and clinical behavior of young women in the cohort NORA study PATIENTS AND METHODS: From 2000-2002, patients (N > 3500) were enrolled at 77 Italian hospitals. Women aged ≤50 years (N = 1013) were stratified into age groups (≤35, 36-40, 41-45, and 46-50 years). The relationship between age and patient characteristics, cancer presentation, and treatment was analyzed. RESULTS: Younger women more frequently had tumors with ER/PgR-negative(χ(2) = 7.07; P = .008), HER2 amplification (χ(2) = 5.76; P = .01), and high (≥10%) Ki67 labelling index (χ(2) = 9.53; P = .002). Positive nodal status, large tumors, and elevated Ki67 all associated with the choice for chemotherapy followed by endocrine therapy in hormone receptor-positive patients (P < .0001). At univariate analysis, ER-ve status, chemotherapy and age resulted as the only statistically significant variables (HR = 2.02, P = .004, and >40 versus ≤40, P < .0001, resp.). At multivariate analysis, after adjustment for significant clinical and pathological factors, age remains a significant prognostic variable (HR = 0.93, P = .0021). CONCLUSION. This cohort study suggests that age per sè is an important prognostic factor. The restricted role of early diagnosis and the aggressive behavior of cancer in this population make necessary the application of targeted medical strategies crucial.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Adjuvant treatment of early breast cancer: do the St Gallen recommendations influence clinical practice? Results from the NORA study.

BACKGROUND: The NORA study is a prospective longitudinal cohort study aiming at investigating treatment in patients with early breast cancer. Here, we present the impact of the St Gallen recommendations on clinical practice. PATIENTS AND METHODS: We compared adjuvant strategies in patients enrolled in 2000-2002 to those in 2003-2004 to verify the impact of the 2003 St Gallen recommendations. RESULTS: The use of aromatase inhibitors (AIs) doubled: 65/629 patients (10.3%) vs 100/458 patients (21.8) (P < 0.0001). Following chemotherapy, AIs were administered in 8.5% of the retrospective cohort and in 15.1% of the prospective one (P < 0.0001). The use of taxanes plus hormones dropped (P = 0.0026), but not when used as single agents. A marked increase was observed in the use of anthracycline-based chemotherapy (46.3% vs 65.2%), mainly three-drug regimens (33.3% vs 46.6%). CONCLUSION: Our results suggest that the St Gallen recommendations have had a major impact on clinical practice.

Breast cancer in elderly women: a different reality? Results from the NORA study.

BACKGROUND: The incidence of breast cancer increases with age, and the disease affects many older women; however, attitudes about prevention and treatment of breast cancer vary based on the patient's age. Older women have less access to clinical trials and fewer opportunities for treatment with innovative therapies. The National Oncological Research observatory on Adjuvant therapy in breast cancer (NORA) study was a cohort study designed to obtain information about adjuvant strategies for treatment of breast cancer after surgery, patterns of recurrence, and possible correlations between cancer-related events and biological factors. PATIENTS AND METHODS: This report describes patient characteristics, disease status, and local and systemic adjuvant treatments in a population of breast cancer patients aged >or=65 years. The NORA study consecutively enrolled >3500 patients from 2000 through 2002 at 77 Italian hospitals; of these, 1085 were aged >or=65 years. Data on patient characteristics, cancer presentation, and treatments were analyzed to identify possible relationships between these factors and age. RESULTS: The findings indicate that age is significantly related to later diagnosis and different patterns of treatment. Choice of adjuvant systemic treatment was primarily related to hormone receptor status and tumor stage but was strongly influenced by the patient's age; there was a proportional relationship between endocrine treatment and increasing age. Cyclophosphamide, methotrexate, and 5-fluorouracil as well as anthracyclines were widely used, but the use of taxanes was limited to a very small percentage of patients. CONCLUSIONS: The findings of the NORA study may help to change attitudes that currently exclude a significant proportion of breast cancer patients from secondary prevention policies, more active treatment strategies, and clinical research trials based on age.