[Third degree atrio-ventricular blockade during a myocarditis occurring under anti-PD1 : Case report and literature review]. / Bloc atrio-ventriculaire de grade III compliquant une myocardite au décours d'un traitement par anti-PD1 : observation d'un cas et revue de la littérature.

INTRODUCTION: Immune Checkpoint Inhibitor (ICI) therapy is now a standard of care in numerous cancers with very promising results. Nevertheless, adverse events, and especially immune-related adverse events (irAEs) not reported during clinical trials, are emerging and can be life-threatening. OBSERVATION: We report here a teachable case of a 80 year-old man, of third-degree atrioventricular block consecutive to myocarditis associated with the administration of nivolumab (anti-PD1) monotherapy. CONCLUSION: Myocarditis occurring during ICI treatment is a rare but potentially lethal event. Daily serum troponin level seems to predict ICI-related myocarditis but interpretation could be difficult in the context of associated myositis. Echocardiography and cardiac MRI are also useful but can remain negative. Electrocardiogram is a cornerstone of myocarditis diagnosis. In case of cardiac involvement, continuous heart rhythm monitoring should be performed in addition to the administration of high-dose corticosteroids therapy and the cessation of ICI therapy. Add-on treatments should be discussed with a well-trained multidisciplinary team.

[Therapeutic strategies in patients undergoing surgery for non-small cell lung cancer. Results of the ESCAP-2011-CPHG study, promoted by the French College of General Hospital Respiratory Physicians (CPHG)]. / Stratégies thérapeutiques chez les patients opérés pour un carcinome bronchique non à petites cellules. Résultats de l'étude ESCAP-2011-CPHG réalisée par le Collège des pneumologues des hôpitaux généraux (CPHG).

BACKGROUND: The aim of ESCAP-2011-CPHG, promoted by the French College of General Hospital Respiratory Physicians, was to describe therapeutic strategies in lung cancer in the first 2 years after diagnosis, in a real-life setting. This article focuses on patients undergoing surgical management of a non-small cell lung cancer (NSCLC). METHODS: A prospective multicentre study was conducted in 53 French general hospitals. For each patient with lung cancer diagnosed in 2010, a standardised form was completed following each change in treatment strategy up to 2 years after diagnosis. RESULTS: Overall, 3418 of the 3943 included patients had NSCLC. 741 patients (21.7%) underwent curative surgery (stage 0-II, IIIA, IIIB, and IV: 65%, 27%, 3% and 5%, respectively). The therapeutic strategy changed less often in surgical than non-surgical patients and average follow-up time was longer: 23.3 months (SD: 9.3) versus 10.4 months (SD: 9.5) for non-surgical patients. Among patients with a surgical first strategy (92.6% of surgical patients as a whole), 56.9% did not receive any other treatment, 34.7% received chemotherapy, 5.9% radio-chemotherapy, 2.6% radiotherapy. At the end of follow-up, 55.8% were still alive without any other strategy, 13.1% had died, and 31.1% had received at least one more strategy. Among patients with a surgical second strategy, 63% had received chemotherapy alone during the first strategy. CONCLUSIONS: ESCAP -2011- CPHG assessed everyday professional practice in the surgical management of NSCLC in general hospitals. It pointed out the discrepancies between current guidelines and the therapeutic strategies applied in real life conditions.

Impact of high-fat feeding on basic helix-loop-helix transcription factors controlling enteroendocrine cell differentiation.

BACKGROUND AND OBJECTIVES: Gut hormones secreted by enteroendocrine cells (EECs) play a major role in energy regulation. Differentiation of EEC is controlled by the expression of basic helix-loop-helix (bHLH) transcription factors. High-fat (HF) feeding alters gut hormone levels; however, the impact of HF feeding on bHLH transcription factors in mediating EEC differentiation and subsequent gut hormone secretion and expression is not known. METHODS: Outbred Sprague-Dawley rats were maintained on chow or HF diet for 12 weeks. Gene and protein expression of intestinal bHLH transcription factors, combined with immunofluorescence studies, were analyzed for both groups in the small intestine and colon. Gut permeability, intestinal lipid and carbohydrate transporters as well as circulating levels and intestinal protein expression of gut peptides were determined. RESULTS: We showed that HF feeding resulted in hyperphagia and increased adiposity. HF-fed animals exhibited decreased expression of bHLH transcription factors controlling EEC differentiation (MATH1, NGN3, NEUROD1) and increased expression of bHLH factors modulating enterocyte expression. Furthermore, HF-fed animals had decreased number of total EECs and L-cells. This was accompanied by increased gut permeability and expression of lipid and carbohydrate transporters, and a decrease in circulating and intestinal gut hormone levels. CONCLUSIONS: Taken together, our results demonstrate that HF feeding caused decreased secretory lineage (that is, EECs) differentiation through downregulation of bHLH transcription factors, resulting in reduced EEC number and gut hormone levels. Thus, impaired EEC differentiation pathways by HF feeding may promote hyperphagia and subsequent obesity.

[Using French national health insurance data for non-specific monitoring on Reunion Island]. / Utilisation des données de la Caisse générale de Sécurité sociale de la Réunion dans le cadre de la surveillance non spécifique.

BACKGROUND: In Reunion Island, non-specific surveillance developed mainly in 2009 and was based on the activity of hospital emergency department, emergency calls and mortality. From March 2010, a new surveillance was implemented in collaboration between the Indian Ocean regional epidemiology unit and the regional office of the National Health Insurance. The system is based on the weekly number of general practitioner consultations and home visits by municipality. This article presents methods of using these data for non-specific monitoring in Reunion Island. MATERIALS AND METHODS: Data analyzed cover consultations and visits to general practitioners and pediatricians for each of the 24 municipalities. Data were received in week S+1 and were updated week by week following the flow of repayments. To perform weekly monitoring, determine monitoring impact and detect any unusual health event, a correction factor was thus calculated and applied for the overall data set and for each municipality. Received data covered 72% of the population of the island. RESULTS: Over the study period from 2005 to 2009, the monthly average of consultations was 80,000 (min: 58,000 - max 12,0000). Two main peaks of activity were noticed throughout the island during the study period, the first one from weeks 4 to 9 of 2006 with a peak of 105,000 consultations in week 8 and the second one from weeks 34 to 41 of 2009 with a peak of 120,000 consultations in week 35. CONCLUSION: The two peaks described in 2006 and 2009 respectively correspond to outbreaks of chikungunya and influenza A(H1N1) 2009. This monitoring study has two main advantages: an almost exhaustive data set corresponding to three-quarters of the Reunion Island population and the geographic analysis by municipality. Positioned alongside other monitoring networks, this system expands the indicators monitored reflecting varying uses of care.

[Metastatic obstruction of the small bowel revealing or complicating squamous-cell lung cancer. Two cases and a review of the literature]. / Occlusion métastatique de l'intestin grêle révélant ou compliquant un carcinome épidermoïde bronchique. Présentation de deux cas et revue de la littérature.

Gastrointestinal metastasis from lung cancer is exceptional and generally asymptomatic. Other secondary localizations are often present. Metastastic dissemination may involve any portion of the gastrointestinal tract. Clinical expression is variable: dysphagia, anemia, bowel obstruction, peritonitis. Surgical treatment may be indicated in selected patients. We describe the cases of two patients who developed obstruction of the small bowel due to metastases from squamous-cell lung cancer. Bowel obstruction was in the inaugural sign in the first patient. Mesenteric metastasis was associated in the second patient.

Transcriptional pattern of genes coding for the proteolytic system of Lactococcus lactis and evidence for coordinated regulation of key enzymes by peptide supply.

The transcription of 16 genes encoding 12 peptidases (pepC, pepN, pepX, pepP, pepA, pepF2, pepDA1, pepDA2, pepQ, pepT, pepM, and pepO1), P(I) and P(III) proteinases (prtP1 and prtP3), and three transport systems (dtpT, dtpP, and opp-pepO1) of Lactococcus lactis MG1363 was analyzed in response to different environmental factors. Promoter fusions with luciferase reporter genes and/or mRNA analysis were used to study the effects of sugar sources, growth at 37 degrees C, and peptide supply on the transcription of these genes. Only transcription of the pepP gene is modulated by the source of sugar. The presence of potential catabolite-responsive element (CRE) boxes in its promoter region suggests that expression of this gene is directly controlled by catabolic repression. Elevated temperature had no significant effect on the level of transcription of these genes. prtP1, prtP3, pepC, pepN, pepX, and the opp-pepO1 operon are the most highly expressed genes in chemically defined medium, and their expression is repressed 5- to 150-fold by addition of peptide sources such as Casitone in the medium. Moreover, the transcription of prtP1, prtP3, pepC, pepN, and the opp-pepO1 operon is repressed two- to eight-fold by the dipeptides leucylproline and prolylleucine. The transcription of pepDA2 might also be repressed by the peptide sources, but this effect is not observed on the regulation of dtpT, pepP, pepA, pepF2, pepDA1, pepQ, pepT, pepM, and the dtpP operon. The significance of these results with respect to the functions of different components of the proteolytic system in L. lactis are discussed.

Genetic and biochemical characterization of a high-affinity betaine uptake system (BusA) in Lactococcus lactis reveals a new functional organization within bacterial ABC transporters.

The cytoplasmic accumulation of exogenous betaine stimulates the growth of Lactococcus lactis cultivated under hyperosmotic conditions. We report that L. lactis possesses a single betaine transport system that belongs to the ATP-binding cassette (ABC) superfamily of transporters. Through transposon mutagenesis, a mutant deficient in betaine transport was isolated. We identified two genes, busAA and busAB, grouped in an operon, busA (betaine uptake system). The transcription of busA is strongly regulated by the external osmolality of the medium. The busAA gene codes for the ATP-binding protein. busAB encodes a 573-residue polypeptide which presents two striking features: (i) a fusion between the regions encoding the transmembrane domain (TMD) and the substrate-binding domain (SBD) and (ii) a swapping of the SBD subdomains when compared to the Bacillus subtilis betaine-binding protein, OpuAC. BusA of L. lactis displays a high affinity towards betaine (K(m) = 1.7 microM) and is an osmosensor whose activity is tightly regulated by external osmolality, leading the betaine uptake capacity of L. lactis to be under dual control at the biochemical and genetic levels. A protein presenting the characteristics predicted for BusAB was detected in the membrane fraction of L. lactis. The fusion between the TMD and the SBD is the first example of a new organization within prokaryotic ABC transporters.

An aminoacyl-tRNA synthetase paralog with a catalytic role in histidine biosynthesis.

In addition to their essential catalytic role in protein biosynthesis, aminoacyl-tRNA synthetases participate in numerous other functions, including regulation of gene expression and amino acid biosynthesis via transamidation pathways. Herein, we describe a class of aminoacyl-tRNA synthetase-like (HisZ) proteins based on the catalytic core of the contemporary class II histidyl-tRNA synthetase whose members lack aminoacylation activity but are instead essential components of the first enzyme in histidine biosynthesis ATP phosphoribosyltransferase (HisG). Prediction of the function of HisZ in Lactococcus lactis was assisted by comparative genomics, a technique that revealed a link between the presence or the absence of HisZ and a systematic variation in the length of the HisG polypeptide. HisZ is required for histidine prototrophy, and three other lines of evidence support the direct involvement of HisZ in the transferase function. (i) Genetic experiments demonstrate that complementation of an in-frame deletion of HisG from Escherichia coli (which does not possess HisZ) requires both HisG and HisZ from L. lactis. (ii) Coelution of HisG and HisZ during affinity chromatography provides evidence of direct physical interaction. (iii) Both HisG and HisZ are required for catalysis of the ATP phosphoribosyltransferase reaction. This observation of a common protein domain linking amino acid biosynthesis and protein synthesis implies an early connection between the biosynthesis of amino acids and proteins.

[Surgical pulmonary biopsies in patients with HIV infection: results apropos of a series of 21 cases]. / Biopsies pulmonaires chirurgicales chez les patients infectés par le VIH: résultats à propos d'une série de 21 cas.

This retrospective study reports the results of surgical lung biopsies in 21 patients infected by HIV. Diagnostic was assessed by surgical lung biopsies in 66% of cases with a 5% immediate post-operative mortality and a 80% survival rate after one month. Therapeutic management was modified in 38% of cases. These results are in concordance with previously published literature and emphasize that such a procedure should only be performed after other diagnostic procedures, including at least a bronchial endoscopy associated to a BAL and/or transbronchial biopsies.

Pleural and lung cryobiopsies during thoracoscopy.

Cryotherapy through rigid bronchoscopy has been used in the past three years in the treatment of endobronchial tumors. We performed pleural and lung cryobiopsies during thoracoscopy. The hemostatic properties and the quality of the histopathologic specimens obtained using this technique offer an innovative approach to the diagnosis of pleural effusion with associated lung disease.

[Malignant non-Hodgkin's lymphoma of tracheo-bronchial sites]. / Lymphome malin non hodgkinien à localisations trachéo-bronchiques.

The case of a 66 years old male patient with multiple tracheal and bronchial lesions of non-Hodgkin lymphoma is reported. This was a disseminated form of low-malignancy lymphoma, as shown by histological findings. The lesions disappeared after 10 courses of chemotherapy, and no sign of recurrence was observed during a 3 years' follow-up. It is concluded that the prognosis of this disease depends on histology rather than on anatomical spread.

Bronchoscopic cryotherapy for airway strictures caused by tumors.

This study reports an application of cryosurgery for the treatment of tracheobronchial tumors. Bronchoscopic cryotherapy can be applied in patients who are not candidates for other traditional therapy. The technique utilizes a nitrous oxide cryoprobe, introduced through a rigid bronchoscope. The principal feature of this probe is to be nonrigid. The cryodestruction is controlled by an impedance metric method. The study group consisted of 27 patients ranging in age from 39 to 88 years. The most frequent diagnosis was squamous cell carcinoma (14). For malignant tumors, the objective was obtained in 13 cases out of 21. Cryotherapy successfully destroyed five benign granulomas. Four or six days after cryotherapy, bronchial biopsy specimens usually showed a necrotic substance, and tumoral tissues were entirely destroyed. The time of survival is probably extended and the quality of life bettered. Most visible tumors are now reached with a flexible cryoprobe, inserted in a flexible bronchoscope.

Fluorescence as a guide to bronchial biopsy.

The presence of fluorescence was assessed in 34 unselected patients undergoing bronchoscopy, 11 of whom suffered from bronchial carcinoma. Bronchoscopic inspection was carried out with white light and then repeated with blue light after the injection of 2 ml of 10% sodium fluoresceinate. Fluorescence was graded visually. Seventy six pairs of biopsy specimens were obtained. Of 38 specimens from non fluorescent areas, histological appearances were normal in 34. Slight inflammation was observed in three biopsy specimens, and in one there was evidence of tumour even though the specimen was obtained some distance from the primary tumour. Of 38 biopsy specimens from fluorescent areas, histological examination showed appearances of moderate inflammation in 10, severe inflammation in 10, tuberculosis in one, and carcinoma in 11. In six instances histological appearances were normal. Five normal subjects who were smokers were also examined by the same technique. Appearances of metaplasia were found more often in areas showing fluorescence than in areas not showing fluorescence. Bronchial fluorescence is considered to be related to alteration in vascularity and is not specific for carcinoma. The most fluorescent areas are generally the most pathological and visible tumour is very fluorescent, but moderate degrees of fluorescence are difficult to interpret. Biopsy of every fluorescent area seems excessive.

[Anatomopathology, physiopathology and treatment of the emphysematous disease of infants (apropos of an experience with 133 surgically treated cases)]. / Remarque sur l'anatomopathologie, la physiopathologie et le traitement de la maladie emphysemateuse du petit enfant (à propos d'une expérience de 133 cas opérés).

Infantile and childhood lobar pulmonary emphysema (LPE) has finally become a rather straightforward problem after 28 years experience and the important statistics published. Contrary to adult emphysema, and leaving aside the particular aspects of causal lesions, the pediatric form is usually a unilateral lobar or infralobar disorder, and therefore lends itself to surgical treatment.

Safety and clinical effectiveness of intracranial pressure monitors for purposes of Medicare coverage.

The National Center for Health Care Technology, authorized by Congress in 1978, has established a mechanism within the Public Health Service for responding to medical and scientific issues related to Medicare reimbursement. NCHCT relies primarily on the private sector for such evaluations. The process established by NCHCT includes participation by appropriate federal agencies, medical speciality societies, and health insurance and manufacturing associations. A typical NCHCT assessment recently completed is that of intracranial pressure monitors. The NCHCT assessment concludes that ICP monitors provide a means of measuring ICP, as well as aid the neurosurgeon in selecting an appropriate course of therapy for many intracranial diseases (e.g., infections, hemorrhage, trauma, tumor, and hydrocephalus). Invasive ICP monitoring devices are judges to be sufficiently developed for clinical use and will provide accurate measurements of ICP.

[Detection of malignant melanoma metastases. Value of radioisotopic methods (author's transl)]. / Détection des métastases de tumeurs mélaniques. Valeur des méthodes isotopiques.

No single radioisotopic exploration is capable of detecting metastases of malignant melanomas, but the successive use of three different scintigraphic techniques (liver, bone and 67Ga citrate) has increased the detection rate from 55 to 68%. Since these metastases are small and may develop anywhere in the body, several methods must systematically be combined, particularly when one of them gives normal results. Experience has shown that 13% of metastases would have passed unnoticed if the three scintigraphic techniques had not been used.

[Simultaneous or successive locations carcinomas of head and neck (author's transl)]. / Cancers multiples, simultanés et successifs, des voies aéro-digestives supérieures.

204 simultaneous or successive locations of carcinoma were observed and analysed in a series of 1992 cases of head and neck carcinomas for 15 years (10.24 p. 100). Simultaneous carcinomas appeared electively in single anatomical area: hypopharynx, oropharynx, endolarynx. Successive carcinoma on the other hand are developed in adjacent anatomical sites. An oesophagal location worsens the prognosis; the related facts and rules are analysed for their frequency. An early detection II counselled and their pathogenesis is discussed.

Treatment of heroin-dependent persons with antagonists: current status.

Naltrexone is an important new pharmacologic adjunct to the treatment of heroin dependence. The development of naltrexone has been nurtured in the mature recognition that simple detoxification or simple opiate replacement therapy is not appropriate for every heroin addict. Our current data indicate that naltrexone is safe and effective. Its use may be limited to a minority of addicts, those who are highly motivated and opiate free, because patient compliance has been a major problem with which clinicians using naltrexone have had to contend. Patient compliance is a problem, because there are no immediate consequences to the patient for stopping his naltrexone regimen. Side effects from naltrexone have been minimal and have occurred in a minority of patients. They consist primarily of gastrointestinal symptoms, including nausea and occasionally abdominal pain.

A comprehensive psychiatric approach to drug dependence.

A comprehensive approach to the treatment of drug-abusing and dependent persons is proposed based on a knowledge of the psychopathology and the psychodynamics of drug abuse and psychological dependence. The role of psychiatric understanding of drug dependence is historically developed. The recent contributions of clinicians and researchers evolving from psychoanalytic ego theory as well as psychopharmacological orientation are discussed. The authors argue that categorizing people in terms of overt behavior - drug abuse or dependence - is not sufficient. Specific psychopathological and/or psychodynamic conditions should be diagnosed and utilized as the basis for treatment.

[Carcinoma of the upper respiratory and digestive tracts. Histopathology and chemotherapy in 300 cases (author's transl)]. / Chimiothérapie et histopathologie des carcinomes des voies aéro-digestives supérieures. A propos de 300 cas.

The pathological review of 300 larynx hypopharynx and pyriform sinus carcinoma was done systematically. The results expressed according to the absence or the type of chemotherapy (Bleomycine alone or O.M.B. association) are analysed. There is no difference for the epithelial proliferation but the collagenous part of stroma was enhanced by therapeutic. The foreign body granulomas are related to the tumor maturation (keratinization).