Multidisciplinary real-world management of metastatic castration-sensitive prostate cancer: A French national study (PROFILE study).

While androgen deprivation therapy (ADT) has been the standard of care for patients with metastatic castration-sensitive prostate cancer (mCSPC), recent strategies like intensification of systemic treatment (Rozet et al., 2020) (i.e. adding another treatment to ADT) and radiotherapy have improved overall survival. PROFILE, a national retrospective multicentric real-world study, involved patients with mCSPC recruited by medical oncologists, urologists, and radiation oncologists, and who started treatment between November 2020 and May 2021. Patients by sites were included consecutively. Data were collected from medical records. Primary objectives were to: (1) describe retrospectively the characteristics of whole population of patients with mCSPC as well as subgroups defined by prognostic factors in France at diagnosis; (2) identify current practices for managing mCSPC in a real-life clinical setting. Among the 416 patients with mCSPC included in the PROFILE study, 315 (76%) were synchronous (metastasis at the initial diagnosis) and 101 (24%) were metachronous patients (metastasis diagnosed post-progression). A majority (83% of synchronous and 73% of metachronous patients) received an intensified systemic treatment (ADT plus ARSI [androgen-receptor signaling inhibitors]±chemotherapy±primary tumour radiotherapy±metastasis-directed therapy [MDT]), while only 40% of low-volume patients received prostate radiotherapy. This study depicts the standardization of new therapeutic strategies for patients with mCSPC in France with most of them receiving an intensified treatment, mainly with ADT+ARSI (64% of synchronous intensified patients and 76% of metachronous intensified patients). Most of patients were assessed using conventional imaging (CT scan and/or bone scan). Overall, PROFILE results are in line with French and European guidelines for diagnosis, management, and follow-up of such patients (Rozet et al., 2020; Cornford et al., 2021).

[Antineoplastic drug induced nausea and vomiting: What is the clinical practice in 2018? An update of AFSOS clinical guidelines]. / Nausées-vomissements induits par les traitements anti-cancéreux (NVITAC) : quelle prise en charge en 2018 ? Mise à jour du référentiel AFSOS.

Antineoplastic drug induced nausea and vomiting (ANDINV) (previously named: Chemotherapy-induced nausea and vomiting [CINV]) are one of the most feared adverse effect for patients who begin treatment with anti-cancer treatments and their bad control have a negative impact in the management of these patients. In this review article, it is proposed an update of French-speaking Association for oncologic supportive care (AFSOS) clinical practice of CINV guidelines. This update became necessary for several reasons: newly available anti-emetic drugs; new data published about individual risk factors of CINV; new antineoplastic agents available; changing in emetic risk levels for some molecules in the international guidelines. To address these guidelines, the various clinical presentations of ANDINV and their intensity classification are discussed. Then, the different therapeutic solutions are presented: classes of conventional drug therapies, complementary therapies and advice to patients. Then, the implementation of primary prophylaxis are presented in four steps: (1) to evaluate the emetic risk level of antineoplastic agent; (2) to set the emetic risk level of antineoplastic protocols; (3) to set types of antiemetic drugs to implement; (4) "Outperform" prophylaxis in case of individual risk factors. Finally, implementation of secondary prophylaxis and rescue treatments are adressed.

[Opioid switch and change of route of administration in cancer patients treated by morphine]. / La morphine dans le cadre du changement d'opioïdes ou de voie d'administration, chez l'adulte avec une douleur due au cancer.

This paper reviewed the 2002 guidelines established by the National Federation of Cancer Centres. A group of experts nominated by the 3 French Societies involved in the treatment of cancer pain (AFSOS, SFAP, SFETD), established new guidelines ratios for morphine switching and/or changing of route of administration, in patients for whom either pain was not adequatly managed or adverse effects were unbearable. After a rapid reminder of the pharmacokinetics and metabolism properties of morphine, experts explained why the theory of opioid rotation (oxycodone, hydromorphone, fentanyl, methadone, tapentadol) using fixed equianalgesic ratios is not any more appropriate for a secure clinical practice. In the light of recent publications enhancing our knowledge on the efficacy of new drug switching ratios and for changing the route of administration of morphine, the group of experts recommended to use reconsidered switching ratios favoring security upon efficacy, to minimize overdosing and adverse effects. Consequently, after the new conversion ratio (using slow release opioids) was applied, a second titration should be done by means of normal release rescue formulations for breakthrough pain episodes. A smartphone App. OpioConvert® will be available for rapid and secure dose conversions.

Supportive Care Organization in France: a national in-depth survey among patients and oncologists.

PURPOSE: Medical doctors' (MDs), but not patients', perception of supportive care in cancer (SCC) in France has been previously assessed in a national survey. This study evaluated MDs and patients' perceptions of the SCC organization and implementation in France. METHODS: The French SCC Association conducted two observational studies: study 1 (S1), containing a 30-point questionnaire sent to 2263 MDs, and study 2 (S2), containing a 40-point questionnaire sent to 2000 patients. RESULTS: Overall, 711 MDs completed S1 and 1562 patients completed S2. In S1, 81% of MDs reported relying on a SCC organization and 76% attended SCC multidisciplinary discussions. MDs considered palliative (98%), psychological (98%), and social care (98%) as the top 3 SCC areas of importance for patients. In contrast, patients' priorities were psychology (61%), nutrition (55%) and organization of intake consultations (55%). The concept of SCC was familiar to 34% of patients; according to MDs, this concept was introduced mainly by MDs (78%) and admission nurses (41%). Outpatients identified as professional resources for SCC information general practitioners (84%), nurses (58%), and pharmacists (52%). Patients reported supportive treatment being prescribed in 63% of cases, with 64% receiving information on the negative side-effects. Among MDs, 87% reported proposing palliative and 41% adjuvant SCC treatment. Furthermore, 72% of MDs recommended SCC treatment at the metastatic stage, and 36% immediately following diagnosis. DISCUSSION: Oncologists play a vital role in enhancing SCC efficacy. This can be increased by implementing a multidisciplinary integrated approach or by assuring the availability of patient information.

[Constipation and cancer: Current strategies]. / Constipation et cancer : stratégies actuelles.

Digestive disorders, in particular constipation, are symptoms very often reported by cancer patients as having a major impact on their quality of life. An accurate diagnosis of bowel delayed transit and defecation disorders is required to best adapt therapeutic management. Constipation associated with cancer may be related to several causes, which can be placed in three nosological categories that sometimes overlap: chronic constipation prior to cancer and having its own evolution; constipation related to the cancer condition, in particular the occlusive syndrome, and constipation induced by cancer therapies. The stricter application of diet and lifestyle measures is often necessary and sometimes sufficient. Laxative drug treatments come under various galenic forms and administration routes and must be selected according to the clinical features of constipation. Surgical management can be indicated in case of ileus or pelvic static disorders. In the case of refractory constipation induced by opioids and within the framework of palliative care to treat an advanced pathology, a peripheral morphinic antagonist can offer fast symptom relief. A way forward to improve the patients' quality of life could be to identify the contributing factors (in particular, genetic factors) to determine which patients are the more at risk and anticipate their management.

Chemoradiotherapy with FOLFOX plus cetuximab in locally advanced oesophageal cancer: The GERCOR phase II trial ERaFOX.

BACKGROUND: To determine efficacy and toxicity of radiation therapy combined with oxaliplatin, 5-fluorouracil, and folinic acid (FOLFOX) and cetuximab in patients with locally advanced oesophageal cancer. PATIENTS AND METHODS: Patients with stage III oesophageal or gastro-oesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received FOLFOX and weekly cetuximab on week 1-10 with concurrent radiotherapy (50.4 Gy in 30 fractions) on week 5-10. Primary end-point was clinical overall response rate (ORR). An ORR rate of more than 50% was expected. RESULTS: Among the 79 included patients, clinical ORR was 77% with 40% complete responses. Median overall survival and progression-free survival were 21.6 and 11.3 months, respectively. The most common grade III-IV toxicities observed during experimental chemoimmunotherapy followed by chemoradiation included neutropenia (28%), oesophagitis (12%), rash (11%), and allergy (9%). There was one treatment-related death due to oesophagitis with gastrointestinal bleeding. CONCLUSIONS: Cetuximab-FOLFOX regimen combined with radiotherapy demonstrated its efficacy and was well tolerated. Unfortunately, these results were not confirmed in two recent phase III studies.

Venous thromboembolism: What pharmacists know? What do they need?

INTRODUCTION: Venous thromboembolism is common in cancer. Low-molecular weight heparins are recommended for prolonged treatment (3-6 months or more if the cancer is active) and prevention of recurrence of venous thromboembolism in cancer. Community pharmacists are often faced with questions from patients. The main objective of this study was to describe the organization, practices and knowledge of pharmacists in care of venous thromboembolism in cancer patients. METHODS: A descriptive survey was conducted electronically in October and November 2013 with pharmacists in the Champagne-Ardenne region. The questionnaire collected data on the general organization of the pharmacy, management of outpatients with cancer and thrombosis, and the level of knowledge regarding recommendations on the management of thrombosis in patients with cancer. RESULTS: The participation rate was 31.6%. In 93% of cases, pharmacists had no particular expertise in oncology and/or supportive care. In addition, 96% did not know the existence of recommendations for "thrombosis in cancer." Finally, 49% gave the correct answer to the case report (low-molecular weight heparins). CONCLUSION: Training sessions on the management of venous thromboembolism in cancer are currently available to pharmacists in the region. A new assessment of knowledge will be performed at the end of the year 2014. This regional experience is now extended to a national level (all French regions).

Management of anemia and iron deficiency in a cancer center in France.

PURPOSE: Anemia affects most patients treated for cancer by chemotherapy. It is a known major contributor to fatigue and loss of quality of life and is likely to have a negative effect on prognosis and mortality from cancer. The main purpose of this study was to characterize the management of anemia and iron deficiency in a French oncology day-care center. METHODS: A retrospective study was conducted between May and November 2012 in the oncology day unit of the Jean Godinot Cancer Center (France). The 133 patients included were all over the age of 18 and being treated by chemotherapy and had mild, moderate, or severe anemia. RESULTS: Over half (58%) the patients were shown to be receiving no specific treatment for anemia. Iron balance was assessed in 71 patients and iron deficiency diagnosed in 37. Stepwise logistic regression showed that patients with severe to moderate anemia were nearly four times more likely to have an iron balance assessment than those with mild anemia (OR, 3.78; 95% CI, 1.84-7.76; P = 0.0003). Classical logistic regression shows that older patients (≥70) are three times less likely to have an iron balance assessment than patients <70 years (OR, 0.32; 95% CI, 0.12-0.86; P = 0.06). CONCLUSION: An ideal medical setting for the management of anemia and iron deficiency, and the associated quality-of-life concerns, has yet to be defined for patients with cancer. Screening and treatment of mild to moderate anemia are inadequate, despite the advent of erythropoiesis-stimulating agents. Large scale, multicenter studies are required to define a clear medical framework for the management of anemia and iron deficiency.

Granocyte-colony stimulating factor (G-CSF) has significant efficacy as secondary prophylaxis of chemotherapy-induced neutropenia in patients with solid tumors: results of a prospective study.

AIM: To carry out a prospective, multicenter and observational study describing prophylactic strategies [cycle delay, dose-reduction, (G-CSF) prescription] to prevent recurrence of neutropenic events (NE) in patients with solid tumors, and identify potential predictive factors of NE recurrence. PATIENTS AND METHODS: Patients ≥18 years old with an NE in a previous chemotherapy cycle (cycle A) without G-CSF support, followed for four cycles (B to E) were included in the study. NE was defined as any neutropenia grade 1-4, febrile or not, which impacted on subsequent chemotherapy cycles (cycle delay, or reduction, or prophylactic G-CSF). RESULTS: Data of 548 patients were analyzed, 378 (69%) were female, with a mean (SD) age of 61.7 (12.3) years. WHO PS: 0-1: 88.3%, incidence of breast cancer: 40%, metastatic disease: 53.3%. Following the first NE episode, 44.5% of patients had cycle delay, 22.3% dose reduction and 466 (85%) received prophylactic G-CSF. NE recurrence rates were: 21.2% at cycle B, 18.6% at cycle C, 11.5% at cycle D and 12.9% at cycle E. G-CSF support (hazard ratio: 0.32, 0.24-0.43, p<0.001) was associated with lower NE recurrence. Pegfilgrastim seemed to offer the highest protection (hazard ratio; HR=0.23, 95% CI: 0.16-0.32; p<0.001). CONCLUSION: Secondary G-CSF prophylaxis has significant efficacy in reducing the incidence of NE and should be considered as a valuable option.

Fractionated stereotactic radiotherapy for acoustic neuromas: a prospective monocenter study of about 158 cases.

PURPOSE: To evaluate long-term outcomes and efficacy of fractionated stereotactic radiotherapy in the treatment of acoustic neuromas. MATERIAL AND METHODS: Between January 1996 and December 2009, 158 acoustic neuromas were treated by FSR in 155 patients. They received a dose of 50.4 Gy, with a safety margin of 1-2mm with a median tumor volume at 2.45 mL (range: 0.17-12.5 mL) and a median follow-up duration at 60 months (range: 24-192). RESULTS: FSR was well tolerated in all patients with mild sequelae consisting in radiation-induced trigeminal nerve impairments (3.2%), Grade 2 facial neuropathies (2.5%), new or aggravated tinnitus (2.1%) and VP shunting (2.5%). The treatment failed in four patients (2.5%) who had subsequent surgery respectively at 20, 38, 45 and 84 months post-FSR. The local tumor control rates were respectively 99.3%, 97.5% and 95.2% at 3, 5 and >7-year of follow-up. For initial Gardner-Robertson Grade 1 and 2 ANs, the preservation of useful hearing was possible in 54% of the cases; only Grade 1 ANs had stabilized during the course of the follow-up with 71% >7 years. However, hearing preservation was not correlated to the initial Koos Stage and to the radiation dose delivered to the cochlea. Tinnitus (70%), vertigo (59%), imbalance (46%) and ear mastoid pain (43%) had greatly improved post-FRS in most patients. Tumor control, hearing preservation and FRS toxicity were quite similar in patients with NF2, cystic acoustic neuroma, prior surgical resection and Koos Stage 4 AN. No secondary tumors were observed. CONCLUSION: FSR is a safe and effective therapeutic for acoustic neuromas and could be an alternative to microsurgery. Compared to radiosurgery, there are no contraindications for fractioned doses of stereotactic radiotherapy especially for Stage-4 tumors and patients at high risk of hearing loss.

Implanted carmustine wafers followed by concomitant radiochemotherapy to treat newly diagnosed malignant gliomas: prospective, observational, multicenter study on 92 cases.

OBJECTIVES: Study the feasibility and effectiveness of a treatment associated surgery, intraoperative chemotherapy (carmustine wafers), and concomitant radiochemotherapy (temozolomide) for the management of newly diagnosed, high-grade gliomas. METHODS: Prospective multicenter study conducted in 17 French centers with a total of 92 patients with newly diagnosed malignant glioma treated by surgery, implanted Carmustine wafers (Gliadel(®)) followed by concomitant radiochemotherapy by temozolomide (Temodar(®)). Clinical, imaging, and survival data were collected to study toxicity-induced adverse events and efficacy. RESULTS: A total of 20.6 % presented with adverse events during surgery, potentially attributable to carmustine, including 5 severe infections. Afterwards, 37.2 % of patients showed adverse events during radiochemotherapy and 40 % during adjuvant chemotherapy by temozolomide. We report a 10.5-month, median, progression-free survival and an 18.8-month median overall survival. No significant statistical difference was observed according to age, Karnofsky Performance Scale, or grade of the tumor. A prognostic difference at the limit of the significance threshold was observed according to the extent of the resection. CONCLUSIONS: Multimodal treatment associating implanted carmustine chemotherapy and concomitant radiochemotherapy with temozolomide seems to yield better survival rates than those usually described when carmustine or temozolomide are used alone independently from one another. These interesting results were obtained without increased adverse events and would need to be validated during a phase 3 study.

[The place of general practitioners in cancer care in Champagne-Ardenne]. / Place du médecin généraliste dans le traitement du cancer en Champagne-Ardenne.

INTRODUCTION: In France, general practitioners (GPs) are playing a key role in cancer care since the HPST law and the second national cancer plan. METHOD: A postal questionnaire survey was conducted in Champagne-Ardenne Area to evaluate GPs' satisfaction and needs in cancer management. A questionnaire was sent by mail in March and April 2011 to 1231 GPs. Statistical analysis of the results was done using Sphinx software (France). RESULTS: Participation rate was 33% (n = 405/1231). Most of the participants were male (n = 296; 73%), and the mean age was 51.8 years (s.d.: 9 years). Participants described as acceptable their communication with oncologists (n = 343; 85%), the delay of receiving the multidisciplinary team meeting report (n = 353; 88%) and the patient personalised care plan (n = 319; 81%). However, 69% (n = 269) stated that the communication between GPs and oncologists should improve and 64% (n = 243) were not satisfied with their level of oncology knowledge. CONCLUSION: This study identified important key points that need to be improved in order to strengthen the place of GPs in cancer management.

Prevalence of rotavirus, adenovirus, norovirus, and astrovirus infections and coinfections among hospitalized children in northern France.

From January to December 2007, 973 stool specimens were prospectively collected from children hospitalized for gastroenteritis signs or from neonates and premature cases who were born in two French hospital settings in the north of France. They were tested by rapid enzyme immunoassay (EIA) analyses for rotavirus and adenovirus and by two commercially available ELISA tests for the detection of norovirus and astrovirus. The overall rates of prevalence for rotavirus, norovirus, adenovirus, and astrovirus were 21, 13, 5, and 1.8%, respectively, and they did not significantly differ between the two hospital settings (P=0.12). Mixed virus infections were detected in 32 (3.3%) of the 973 study children and were associated with norovirus in 21 (66%) infants, including 5 premature cases. From fall to spring, norovirus infections accounted for 52% of documented gastroenteritidis viral infections at a time when rotavirus was epidemic, resulting in mixed norovirus and rotavirus gastrointestinal tract infections. Of the 367 documented viral gastroenteritis cases, 15 (4.1%) were identified as nosocomial infections, 5 of which occurred in premature cases. These findings highlight the need to implement norovirus and astrovirus ELISA detection assays in association with rapid EIA rotavirus and adenovirus detection assays for the clinical diagnosis and the nosocomial prevention of gastroenteritis viral infections in pediatric departments.

Curative external beam radiotherapy in patients over 80 years of age with localized prostate cancer: a retrospective rare cancer network study.

PURPOSE: To analyse tolerance and outcome of patients over 80 years of age who choose external beam radiation therapy to the prostate as a curative treatment. METHODS AND MATERIAL: We evaluated acute and late side effects, biological DFS (bDFS) and actuarial survival as well as causes of death in relation to the clinical status including co-morbidity, PSA value, Gleason score and modalities of external radiotherapy in patients with localised prostate cancer >80 years of age. RESULTS: From January 1990 to December 2000, 65 eligible cases (median age: 81) were treated by 12 different participating institutions in the Rare Cancer Network. Tumour stage was T1N0M0, T2N0M0 and T3N0M0 for 10, 40, and 15 patients, respectively. Median follow-up was 65 months (range 22-177). Five-year overall survival rate was 77% with a 5-year bDFS rate of 73%. The incidence of grade 3 early toxicity was 12% and 9% for urinary and digestive tract, respectively. CONCLUSIONS: Radiation therapy given with curative intent is well tolerated in this selected group of patients aged over 80 years with localised prostate cancer. Results in terms of survival do not suggest a deleterious impact of this treatment. Therefore the authors recommend that radiation therapy with curative intent should not be withheld in selected elderly patients with localised prostate cancer.

Noise-induced hearing loss in French police officers.

BACKGROUND: There is a lack of data about police officers' hearing thresholds and the risk of noise-induced hearing loss (NIHL) associated with this occupation. In France, 129,000 national police officers, 96,000 state police force members and 16000 municipal police officers may be affected by occupational noise exposure. AIMS: To evaluate the association between police employment and NIHL. METHODS: We undertook a cross-sectional study using review of medical records. Audiometric and otological data and information on potential confounders were extracted from medical records. Global hearing loss and selective 4000 Hz hearing loss were analysed. RESULTS: Of total, 1692 subjects (887 policemen and 805 civil servants) participated in the study. After adjusting for potential cofounders, police officers were 1.4 times more likely to have a selective 4000 Hz hearing loss than civil servants (95% CI 1.1-1.9). This difference was greater between motorcycle police officers and civil servants (OR = 3; 95% CI 1.4-6.3). CONCLUSIONS: These data suggest that occupational noise exposure in police work, particularly in motorcycle police officers, may induce hearing loss. Noise sources need to be more accurately defined to confirm high-level noise exposures, to better define significant sources of noise and to identify effective solutions.

Incidence of basioccipital hypoplasia in Chiari malformation type I: comparative morphometric study of the posterior cranial fossa. Clinical article.

OBJECT: The chronic tonsillar herniation defining Chiari malformation Type I (CMI) is thought to result from overcrowding of a normally developing hindbrain within a congenitally small posterior cranial fossa (PCF) due to occipital hypoplasia. The goals in the present study were to authenticate the cranioencephalic disproportion in a group of patients with CMI and to discuss new developmental aspects according to which part of the occipital bone was underdeveloped. METHODS: The authors retrospectively examined a group of 17 patients with CMI. Measurements of osteotentorial and neural structures of the PCF were made on MR images of the brain. The results were compared with findings in 30 healthy controls by using the Mann-Whitney U-test. RESULTS: Dimensions of the neural structures did not differ between the 2 groups of patients. The mean length of the basiocciput was significantly shorter in the CMI group (19.4 mm) compared with the control group (25.7 mm; p = 0.0003). The mean diameter of the foramen magnum was larger in the CMI group, but this difference was not statistically significant. The dimensions of the supraocciput and the mean angle of the cerebellar tentorium were identical in the 2 groups. CONCLUSIONS: Data in this study support the idea that occipital hypoplasia is the main cause of overcrowding within the PCF. Basioccipital shortness is a cardinal feature of the resultant shallow PCF and could proceed from a congenital disorder of the cephalic mesoderm of the parachordal plate or occur later in the infancy because of premature stenosis of the sphenooccipital synchondrosis.

Incidence and main factors associated with early unplanned hospital readmission among French medical inpatients aged 75 and over admitted through emergency units.

BACKGROUND: among elderly patients, readmission in the month following hospital discharge is a frequent occurrence which involves a risk of functional decline, particularly among frail subjects. While previous studies have identified risk factors of early readmission, geriatric syndromes, as markers of frailty have not been assessed as potential predictors. OBJECTIVE: to evaluate the risk of early unplanned readmission, and to identify predictors in inpatients aged 75 and over, admitted to medical wards through emergency departments. DESIGN: prospective multi-centre study. SETTING: nine French hospitals. SUBJECTS: one thousand three hundred and six medical inpatients, aged 75 and older admitted through emergency departments (SAFES cohort). METHODS: using logistic regressions, factors associated with early unplanned re-hospitalisation (defined as first unplanned readmission in the thirty days after discharge) were identified using data from the first week of hospital index stay obtained by comprehensive geriatric assessment. RESULTS: data from a thousand out of 1,306 inpatients were analysed. Early unplanned readmission occurred in 14.2% of inpatients and was not related with sociodemographic characteristics, comorbidity burden or cognitive impairment. Pressure sores (OR = 2.05, 95% CI = 1.0-3.9), poor overall condition (OR = 2.01, 95% CI = 1.3-3.0), recent loss of ability for self-feeding (OR = 1.9, 95% CI = 1.2-2.9), prior hospitalisation during the last 3 months (OR = 1.6, 95% CI = 1.1-2.5) were found to be risk factors, while sight disorders appeared as negatively associated (OR = 0.5, 95% CI = 0.3--0.8). CONCLUSIONS: markers of frailty (poor overall condition, pressure sores, prior hospitalisation) or severe disability (for self-feeding) were the most important predictors of early readmission among elderly medical inpatients. Early identification could facilitate preventive strategies in risk group.

Melanoma, past severe sunburns and multiple solar lentigines of the upper back and shoulders.

BACKGROUND: Multiple solar lentigines of the upper back and shoulders (MSLBS) have recently been demonstrated as being associated with intense sunburns in the past. OBJECTIVE: To determine the prevalence of MSLBS among patients with cutaneous melanoma. METHODS: Thisprevalence study was conducted prospectively from October 2003 to November 2004 in a single department of dermatology (Reims University Hospital, north of France). One hundred and twenty-five adult patients, followed up for a cutaneous melanoma, were included, and the prevalence of MSLBS was determined, with comparison of clinical characteristics of patients with and without these lesions. RESULTS: The prevalence of MSLBS among patients with cutaneous melanoma was 37.6%. MSLBS were significantly and independently associated with cutaneous melanoma of the back in multivariate analysis (adjusted odds ratio, OR = 4.3, 95% confidence interval, CI = 1.5-12.3) and with recalled episodes of severe sunburn before the age of 28 (OR = 3.4, 95% CI = 1.3-9.4). CONCLUSION: Large irregularly shaped brown macules of the upper back and shoulders or MSLBS are frequent among adult patients with cutaneous melanoma. They are associated with melanoma located on the upper back. This topographical association further illustrates the relation between past intense sunburns and cutaneous melanoma. MSLBS should be evaluated as an easily recognizable clinical marker of the risk of cutaneous melanoma.

Epidemiological, molecular, and clinical features of enterovirus respiratory infections in French children between 1999 and 2005.

Enteroviruses (EVs) can induce nonspecific respiratory tract infections in children, but their epidemiological, virological, and clinical features remain to be assessed. In the present study, we analyzed 252 EV-related infection cases (median age of subjects, 5.1 years) diagnosed among 11,509 consecutive children visiting emergency departments within a 7-year period in the north of France. EV strains were isolated from nasopharyngeal samples by viral cell culture, identified by seroneutralization assay, and genetically compared by partial amplification and sequencing of the VP1 gene. The respiratory syndromes (79 [31%] of 252 EV infections) appeared as the second most common EV-induced pediatric pathology after meningitis (111 [44%] of 252 cases) (44 versus 31%, P < 10(-3)), contributing to lower respiratory tract infection (LRTI) in 43 (54%) of 79 EV respiratory infection cases. Bronchiolitis was the most common EV-induced LRTI (34 [43%] of 79 cases, P < 10(-3)) occurring more often in infants aged 1 to 12 months (P = 0.0002), with spring-fall seasonality. Viruses ECHO 11, 6, and 13 were the more frequently identified respiratory strains (24, 13, and 11%, respectively). The VP1 gene phylogenetic analysis showed the concomitant or successive circulation of genetically distinct EV respiratory strains (species A or B) during the same month or annual epidemic period. Our findings indicated that respiratory tract infections accounted for the 30% of EV-induced pediatric pathologies, contributing to LRTIs in 54% of these cases. Moreover, the concomitant or successive circulation of genetically distinct EV strains indicated the possibility of pediatric repeated respiratory infections within the same epidemic season.

Active Coxsackieviral B infection is associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial infarction.

OBJECTIVES: In this study, we evaluated the potential direct role of enterovirus (EV) cardiac infections in the pathogenesis of myocardial infarction (MI). BACKGROUND: Enteroviruses (Picornaviridae) have been suspected to play a role in the development of acute MI. METHODS: The presence of EV ribonucleic acid (RNA) sequences and capsid viral protein 1 (VP1) and the virus-mediated focal disruption of dystrophin were retrospectively investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry assays in endomyocardial tissues of patients who died suddenly of acute MI by comparison with similar samples of control patients matched for gender, residence area, and year of death. RESULTS: Enterovirus infection markers were detected in 20 (40%) of 50 patients who died suddenly of MI, 2 (4%) of 50 matched subjects without cardiac disease (p < 0.001), and 4 (8%) of 50 matched patients exhibiting a noncoronary chronic cardiopathy (p < 0.001). All of the EV RNA-positive patients exhibited VP1, which provided evidence of viral protein synthesis activity. The VP1 gene sequences amplified after cloning from myocardial or coronary samples of 8 of the MI patients and showed a strong homology with sequences of coxsackievirus B2 and B3 serotypes. Moreover, in the endomyocardial tissue of these 8 patients, immunohistochemical analyses demonstrated that there was disruption of the sarcolemmal localization of dystrophin in the same tissue areas that were infected by coxsackieviruses. CONCLUSIONS: Our findings demonstrate a significantly higher proportion of active coxsackievirus B cardiovascular infections in patients who suddenly died of MI compared with matched control subjects, suggesting that these EVs may significantly contribute to the pathogenesis of acute MI by a focal disruption of the dystrophin-glycoprotein complex.