PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

Purpose

To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM).

Patients and Methods

A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV).

Results

Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2?C10 weeks. Median overall survival was 8 months (1.2?C50.5 months) and 20 months (4.3?C33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p = 0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p = 0.003).

Conclusions

The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection.     

Analysis of the presence of the GJB6 mutations in patients heterozygous for GJB2 mutation in Brazil

Mutations in the GJB2 gene, mainly 35delG, are responsible for most autosomal recessive inherited genetic hearing loss. The audiometric standard of these hearing losses remains inconsistent and other genes, such as GJB6, have been involved in association with GJB2. The objective of the study was to identify the deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) in patients heterozygous for 35delG/GJB2 and analyze the phenotype they present. 101 patients with mild to profound degree of sensorineural hypoacusis were evaluated. The allele-specific PCR technique was used to identify 35delG. The del(GJB6-D13S1830) and del(GJB6-D13S1854) were identified through the PCR multiplex technique. 90 % of the subjects presented a normal genotype for the analyzed mutations; 6.93 % were shown to be heterozygous for 35delG/GJB2 and 1 % presented compound heterozygosis GJB2/GJB6). The data found reinforced the hypothesis of an interaction of more than one gene as the cause of autosomal recessive genetic hearing loss and emphasized the importance of an early diagnosis for appropriate intervention.     

Réunion de concertation pluridisciplinaire de l’endométriose pelvienne profonde : intérêts et modalités de fonctionnement

Deep endometriosis is a frequent disease that affects reproductive age women. This disease is characterized by the presence of functional endometrium-like tissue outside the uterus. The common sites of extragenital endometriosis are the bowel and the urinary tract. This disease is also associated with infertility. Furthermore, this disease can cause physical and psychological damage. Therefore, it is really important to develop a multidisciplinary approach in the aim to offer the appropriate treatment. The multidisciplinary team approach for endometriosis is developing to improve the understanding of endometriosis and a multidiciplinary committee for endometriosis was developed in our center. During this meeting, gynecologic, digestive surgeons, urologist, radiologist, procreative medical assistance physicians analyse the case. The role of surgery, before, after or as an alternative to in vitro fertilization (IVF) must be defined. The role of the medical treatment before or after the surgery, before the IVF shall be discussed in order to propose the optimal treatment. In fact, radical surgery is no more recommanded and minimaly invasive conservative surgery is encouraged in order to preserve the fertility. The multidisciplinary appraoach permits an appropriate optimal and personalised management of this multifocal disease. The multidisciplinary team approach helps in the developpement of evidence-based guidelines for the diagnosis and management of endometriosis.     

A keyhole gunshot wound to the head: an autopsy case

Considering the high incidence of deaths caused by firearms, forensic pathologists must possess a thorough understanding of the patterns of injuries caused by these weapons. Occasionally, distinguishing between entrance and exit gunshot wounds can be difficult. In our case, a 61-year-old man was killed by a 9 mm calibre gunshot wound to the head during a robbery. At the post-mortem examination the calvarium exhibited an atypical injury that showed both entrance and exit wound characteristics, compatible with a ‘keyhole’ defect of the skull. Keyhole fractures occur when a projectile strikes the cranium tangentially, owing to the vertical and horizontal forces usually generated by the fragmentation of the bullet. Atypically, in our case the bullet showed no fragmentation after the impact with the cranial bones and was still able to result in a keyhole defect. An accurate evaluation of the pattern of atypical lesions found in the post-mortem examination is necessary in order to evaluate the cause and the manner of death.     

Chymase mediates angiotensin-(1-12) metabolism in normal human hearts

Identification of angiotensin-(1-12) [Ang-(1-12)] in forming angiotensin II (Ang II) by a non-renin dependent mechanism has increased knowledge on the paracrine/autocrine mechanisms regulating cardiac expression of Ang peptides. This study now describes in humans the identity of the enzyme accounting for Ang-(1-12) metabolism in the left ventricular (LV) tissue of normal subjects. Reverse phase HPLC characterized the products of ¹²⁵I-Ang-(1-12) metabolism in plasma membranes (PMs) from human LV in the absence and presence of inhibitors for chymase (chymostatin), angiotensin-converting enzyme (ACE) 1 (lisinopril) and 2 (MLN-4760), and neprilysin (SHC39370). In the presence of the inhibitor cocktail, ≥98% ± 2% of cardiac ¹²⁵I-Ang-(1-12) remained intact, whereas exclusion of chymostatin from the inhibitor cocktail led to significant conversion of Ang-(1-12) into Ang II. In addition, chymase-mediated hydrolysis of ¹²⁵I-Ang I was higher compared with Ang-(1-12). Negligible Ang-(1-12) hydrolysis occurred by ACE, ACE2, and neprilysin. A high chymase activity was detected for both ¹²⁵I-Ang-(1-12) and ¹²⁵I-Ang I substrates. Chymase accounts for the conversion of Ang-(1-12) and Ang I to Ang II in normal human LV. These novel findings expand knowledge of the alternate mechanism by which Ang-(1-12) contributes to the production of cardiac angiotensin peptides.     

Evaluation of cardiovascular risk in blood donors: results of the CARDIORISK study in the Parma Transfusion Service

Background

Cardiovascular disease, which is one of the main causes of mortality in industrialised countries, is ever increasingly the focus of prevention. In this study, called “Cardiorisk”, we evaluated cardiovascular risk in the population of blood donors at the Service of Immunohaematology and Transfusion Medicine in Parma.

Patients and methods

Between January 2007 and December 2008, 6,172 consecutive blood donors (aged 35–65 years) were enrolled in this project which entailed calculating each subject’s cardiovascular risk score, based on an evaluation of both unalterable risk factors (age and gender) and modifiable risk factors (total cholesterol, HDL, LDL, triglycerides, glycaemia, smoking, hypertension) as well as anti-hypertensive and/or cholesterol-lowering therapy.

Results

Of the 6,172 donors enrolled in the study, 5,039 (81.7%) had a low cardiovascular risk (score from 0–10), 774 (12.5%) had a moderate cardiovascular risk (score from 11–19) and 359 (5.8%) donors had a high cardiovascular risk (score from 20–28).

Conclusions

In our opinion, the calculation of cardiovascular risk is an important instrument for preventive medicine in blood donors.     

Duration of untreated illness and suicide in bipolar disorder: a naturalistic study

The aim of this naturalistic study was to evaluate the potential influence of the duration of untreated illness (DUI)—defined as the time elapsed between the occurrence of the first mood episode and the first adequate pharmacological treatment with mood stabilizers—on the clinical course of bipolar disorder (BD). Three hundred and twenty outpatients (n = 320) with a DSM-IV diagnosis of BD—either Type I or Type II—were interviewed; their clinical features were collected and they were naturalistically followed-up for 5 years. At the end of the follow-up observation, the sample was subdivided into two groups: one group with a DUI ≤2 years (n = 65) and another group with a DUI >2 years (n = 255). The main demographic and clinical variables were analyzed and compared between the two subgroups of patients using chi-square tests for dichotomous variables or Mann–Whitney U tests for continuous variables. Patients with a longer DUI showed a higher frequency of suicide attempts (Z = −2.11, P = 0.035), a higher number of suicide attempters (χ² = 4.13, df = 1, P = 0.04), and a longer duration of illness (Z = −6.79, P < 0.0001) when compared to patients with a shorter DUI. Moreover, patients with a longer DUI had a depressive first episode more frequently than patients with a shorter DUI (χ² = 11.28, df = 2, P = 0.004). A further analysis performed dividing the total sample into two subgroups on the basis of a DUI of 6 years (corresponding to the median value of the DUI in the study sample) confirmed prior findings. Results indicate a potential association between a longer DUI and a worse outcome in BD, particularly in terms of suicidality, and confirm the clinical relevance of early diagnosis and pharmacological intervention with mood stabilizers in BD.     

The mandatory sentence and Section 2.

Sentencing in homicide depends on how psychiatrists view the issues of Section 2. In most killings that do not involve clear-cut mental disorder, strong emotions and stress play a part. Both can be cited in aid of diminished responsibility. If doctors cite them, however tentatively, it becomes feasible for the court to review any mitigating factors and to choose an appropriate penalty. Otherwise, the mandatory penalty is imposed. Thus doctors, by opining not on the medical but on the legal and moral aspects of Section 2, decide who shall automatically get a life sentence and who shall not. Anomaly and injustice are the results. They would be remedied by the abolition of the mandatory sentence for murder.     

MR-guided aspiration biopsy: needle design and clinical trials

Nonferrous needles of pure brass, titanium, or copper, and ferrous needles of different alloys of stainless steel were analyzed for the size, area, and distribution of the image artifact created when the needles were placed in a 0.6-T magnet. Results demonstrated that a stainless steel prototype needle (type 316) would be visible on magnetic resonance images and would provide an artifact similar to that seen in computed tomographic-guided biopsies. Further testing of this prototype included assessment of the effect on the artifact when changes were made in annealing properties, gauge, length, needle-tip geometry, pulse sequence, and orientation relative to the magnetic field. To date, three human liver biopsies have been successfully and safely performed using a stainless steel type 316 needle.     

A case report of a compressive neuropathy of the radial sensory nerve caused by a ganglion cyst at the elbow

A case of an elbow ganglion cyst with compression of the radial sensory nerve is presented. The mass was noted on the anterior-radial aspect of the elbow after exertional trauma. Symptoms resolved following surgical excision. There has been no recurrence at one year.