Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer.

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Low expression of ANT1 confers oncogenic properties to rhabdomyosarcoma tumor cells by modulating metabolism and death pathways.

Rhabdomyosarcoma (RMS) is the most frequent form of pediatric soft-tissue sarcoma. It is divided into two main subtypes: ERMS (embryonal) and ARMS (alveolar). Current treatments are based on chemotherapy, surgery, and radiotherapy. The 5-year survival rate has plateaued at 70% since 2000, despite several clinical trials. RMS cells are thought to derive from the muscle lineage. During development, myogenesis includes the expansion of muscle precursors, the elimination of those in excess by cell death and the differentiation of the remaining ones into myofibers. The notion that these processes may be hijacked by tumor cells to sustain their oncogenic transformation has emerged, with RMS being considered as the dark side of myogenesis. Thus, dissecting myogenic developmental programs could improve our understanding of RMS molecular etiology. We focused herein on ANT1, which is involved in myogenesis and is responsible for genetic disorders associated with muscle degeneration. ANT1 is a mitochondrial protein, which has a dual functionality, as it is involved both in metabolism via the regulation of ATP/ADP release from mitochondria and in regulated cell death as part of the mitochondrial permeability transition pore. Bioinformatics analyses of transcriptomic datasets revealed that ANT1 is expressed at low levels in RMS. Using the CRISPR-Cas9 technology, we showed that reduced ANT1 expression confers selective advantages to RMS cells in terms of proliferation and resistance to stress-induced death. These effects arise notably from an abnormal metabolic switch induced by ANT1 downregulation. Restoration of ANT1 expression using a Tet-On system is sufficient to prime tumor cells to death and to increase their sensitivity to chemotherapy. Based on our results, modulation of ANT1 expression and/or activity appears as an appealing therapeutic approach in RMS management.

Polymerase chain reaction amplified HTLV-I, HIV-1 and HIV-2 DNA fragments in subjects with mixed retroviral infections.

Serum and peripheral blood mononuclear cells from eight patients from the Ivory Coast with positive screening test results for retroviral infections were studied by serology (ELISA, Western blot (WB), synthetic peptide test), cell co-culture, and polymerase chain reaction (PCR). Two HIV-2 infections with indeterminate interpretation on HIV-1 WB were detected, two were clear dual HIV-1/HIV-2 infections, three were ambiguous mixed HIV-1/HIV-2 infections, and one was a triple retroviral infection by HTLV-I, HIV-1 and HIV-2. Four slow/low HIV-1 strains were isolated at the expense of HTLV-I and HIV-2 strains. The ELISA tests were found to be very sensitive. Indeterminate WB interpretations were frequent (HTLV-I, four; HIV-1, three; HIV-2, two). PCR provided clear evidence of multiple retroviral infections in three cases and enabled interpretation of indeterminate WB samples in three cases. One sample presented a puzzling pattern with positive PCR results for HIV-1 and HIV-2 associated with negative or indeterminate serological results. Thus, our data emphasise the need to analyse serological as well as virological markers to gain better insight on mixed retroviral infections, especially in endemic areas such as West Africa.

[Evaluation of ELISA using A60 antigen from Mycobacterium bovis BCG: specific IGG and IGM in mycobacterial infections]. / Evaluation d'un ELISA utilisant l'antigène A60 de Mycobacterium bovis BCG: IgG et IgM spécifiques au cours des infections mycobactériennes.

The authors have evaluated an ELISA (A60-Tb, Anda biologicals) allowing the detection of specific IgG and IgM against A60 antigen from Mycobacterium bovis BCG during mycobacterial infections. This study included sera from 110 african subjects and from 71 French subjects distributed in 4 clinical groups: 55 tuberculous patients (I), 41 leprous patients (II), 33 pneumopathies (III) and 52 healthy subjects (IV). Serological results were compared taking as reference for the diagnosis of tuberculosis the positivity of culture and/or that of a direct examination, and for leprosy the positivity of a direct examination associated either with a Mitsuda's reaction or with an histopathological examination. IgG were found to be more discriminative than IgM. Considering together the results of groups I and II, the authors found a sensitivity of 95.8 p. cent and a specificity of 75.3 p. cent with threshold of 200 U/ml for specific IgG. Anti-A60 antigen antibodies obtained for groups I and II were significantly higher (IgG: p less than 0.0001; IgM: p less than 0.001) than those observed in other groups. African subjects presented IgG titers higher than those obtained by French subjects (p less than 0.0001). IgM response was more frequent among group II (97.6 p. cent) than group I (21.8 p. cent). However, IgG (26.9 p. cent) and IgM titers (30.8 p. cent) were detected among group IV. This test would allow a control of therapeutic efficacy with an additional interest for classifying borderline forms of leprosy.

[Q fever and fetal death in utero. Two cases]. / Fièvre Q et mort foetale in utero. Deux observations.

Some cases of late abortion occurring after a Coxiella burneti infection, more often with a chronic evolution, have already been mentioned in the literature. We reported here two cases of early abortion, contemporaneous of an acute infection due to C. burneti. Two patients, after a contact, before and at the beginning of the pregnancy, with an animal susceptible to contaminate human beings by C. burneti, presented no clinical symptom characteristic of Q fever. The fetal death for the two cases was found out at the 17th week of amenorrhoea. All the investigations in order to search for an abortion etiology remained negative. Only, the specific serologies showed an acute infection due to C. burneti.

[Sacral tuberculous osteitis]. / Ostéite tuberculeuse sacrée.

The authors report a case of a 5 year old child suffering from isolated sacral tuberculosis which presented as sudden and total loss of function of the left leg. The rarity of this bony site, and the recurrence at nine months of a presacral abscess after 9 months of anti-tuberculous treatment in an HIV negative child, vaccinated with BCG, justify the presentation of this observation.

[Anti-BCG titers of healthy and tuberculous Africans. Use of the indirect immunoperoxidase test]. / Titrage d'anticorps anti-BCG chez des africains sains et tuberculeux. Utilisation d'un test indirect à l'immuno-peroxydase.

This study was intended to assess the presence of antibodies to BCG: immunoglobulin G (IgG) and immunoglobulin M (IgM) in three homogenous african populations: 76 tuberculous patients, 55 adult healthy subjects and 46 newborn. We have used an indirect immuno-peroxidase reaction. Tuberculous patients were clearly distinguished from the other two groups by raised IgG titres, associated with severe clinical and radiological features. In the control population, the IgG anti-BCG were also present, but to a lesser degree. The IgM anti-BCG were seen in high titres (greater than 20 in this study) in healthy adults and patients. The two populations differed significantly (p less than 0.001), nevertheless some healthy adults achieved IgM titres comparable with tuberculous patients. This simple test could be an interesting contributory factor in cases of diagnostic difficult and enables a serological assessment of patients having BCG therapy.

[Mycobacterium africanum (author's transl)]. / Mycobacterium africanum.

A restatement about M. africanum. Diagnosis is based on the aspects of cultures and some biochemical features. Its resistance potentiality is that of M. tuberculosis except for Tb 1 with which resistance is very frequent. It has a rather low experimental virulence and seems to be confined to Africa.

[Salmonellosis in Dakar: bacteriological, clinical, epidemiological and therapeutic aspects. Ten years records (author's transl)]. / Salmonelloses à Dakar. Aspects bactériologiques, cliniques épidémiologiques et thérapeutiques. Bilan de 10 Années.

A study on salmonellosis in Senegal has been carried out in Dakar at the University Hospital of Fann from 1966 to 1976. The authors describe the various methods of isolating the germs (mainly hemoculture and coproculture) and the techniques used for bacteriological research (antibiograms, tests on plasmidic resistance). The results of these investigations, which took the whole of 10 years, are presented below, in accordance with their different aspects: - bacteriological: 1 335 strains of Salmonella have been isolated. Significantly, S. typhi is predominant (56,6 p. 100). But 7 serotypes represent 90 p. 100 of the total strains which are now in existence in Dakar; - clinical: the aspects of these diseases vary: typhoïd fever, encephalitis, diarrheic syndrome, especially among infants, and purulent meningitis, which is generally severe; - therapeutic: 880 strains have been tested with 10 antibiotics. Two groups of Salmonella serotypes are opposed: those which are sensitive (S. typhi, S. typhi murium, S. enteritidis, S. paratyphi C), those which have become resistant (S. stanleyville, S. havana, S. ordonez). The most frequent antibiotype of this kind is ASKCTSu. This is a phenomenon of plasmidic resistance, demonstrated by in vitro experiments; - epidemiological: the lysotypes of 86 strains have been determined. Two epidemiological features must be described: either a stable endemic situation with sensitive strains - or epidemics, lasting several years, with resistant serotypes. Different therapeutic schemes can be used: chloramphenicol for typhoid fever, or sometimes cotrimoxazole, or ampicillin for meningitis. In diarrheic syndrome, symptomatic treatment is enough. Then, the authors give their comments on the special characteristics of salmonellosis in Dakar: - the influence of environment on the various clinical aspects of these diseases: very serious cases of meningitis, typhoid fever, which is more severe than in France, and complications when treatment has gone wrong at the beginning; - antibiograms, which are essential, in order to choose the adequate therapeutics; - and the different aspects of epidemillogy, which are linked to the sensitivity of the serotypes to the most active antibiotics. The existence of several resistant serotypes in Senegal is a real danger: plasmidic resistance could be transferred to S. typhi. In such a situation, epidemiological surveillance of salmonellosis is absolutely necessary, and control of enteric diseases, characterized by foecal transmission, must be carried out, with the techniques available in the country.

[Resistance of Mycobacterium tuberculosis. An 8-year survey in the Poitiers area]. / Résistance de Mycobacterium tuberculosis. Enquête sur 8 ans en région poitevine.

We have studied in Poitiers area from 1977 to 1984 the resistance of 853 Mycobacterium tuberculosis strains to the main anti-tuberculosis drugs. The overall rate of drug resistance was showed to be steady over the years while the primary resistance rate has decreased. The only one drug resistance has concerned para-aminosalicylic acid, streptomycin and isoniazid. Foreigners, most of them Asian people or North-African people, often bear resistant tubercle bacilli (29,03%) compared with French people (9,29%). We encountered drug resistance phenomena essentially among less than 60 years old patients. Drug susceptibility tests remain indispensable for a good epidemiologic supervision at the time of relapses and among patients possibly infected with multiresistant germs.

Combined analysis of Perca fluviatilis reproductive performance and oocyte proteomic profile.

The success of reproduction depends greatly upon gamete quality, especially oocytes which carry most of the molecular material necessary for early embryogenesis. However, it remains difficult to find relevant morphologic and/or biochemical parameters to assess oocyte quality and thus have a reliable prediction of the reproduction performance. To understand which criteria are the most reliable to assess the reproductive success of the Eurasian perch (Perca fluviatilis), we measured 14 parameters characterizing female, spawn, oocyte, and embryonic or larval development on 20 independent spawn. A data analysis allowed the definition of two clusters of spawn with different larval characteristics: the first cluster was composed of spawn which led mainly to strong large larvae presenting a low deformity rate, while the second cluster rather corresponds to spawn leading to smaller and weaker larvae with a higher deformity rate. Moreover, a third cluster (unfertilized spawn) was studied. Our analysis revealed that most of the prefertilization biological traits that we studied appeared poorly relevant to predict larval features, proper embryonic development and deformity occurrences. We thus performed a large scale proteomic analysis to highlight proteins differently expressed in each spawn cluster. A 2D-DIGE study followed by an MS/MS spectrometry allowed the identification of 32 proteins involved in several biological functions and differently expressed between spawn clusters. Among them, proteins involved in cell response to the oxidative stress, as well as energetic metabolism, heat shock proteins and Vitellogenins are of particular interest. Several functions appear specific to a spawn cluster and could thus explain their corresponding reproduction performance. In the future, proteins involved in those cellular mechanisms may constitute molecular markers predictive of the reproduction performance in Perca fluviatilis.

[Rapid detection of rotaviruses in feces. Value of a latex test]. / Détection rapide des rotavirus dans les selles. Intérêt d'un test au latex.

We have sought the presence of rotaviruses in 114 fecal samples. Among them, 14 were from African children and the remainder were samples sent to the Poitiers Hospital Virology Laboratory. Three techniques were applied to each sample: latex agglutination (LTX), electron microscopy (EM) after negative staining and ELISA (Enzyme Linked Immunosorbent Assay). 64% of the samples were negative with the three methods. 19.3% were positive with EM and ELISA. The LTX test showed 16.7% positives among these 19.3%. Our series furnished 5.2% uninterpretable results and 3.5% positive uniquely with the LTX test. ELISA is the most sensitive and the most specific technique but LTX is useful for mass screenings. The advantages of LTX include rapidity, simplicity, reduced instrumentation and low cost price. We suggest the possibility of large scale use of this test in countries with a relatively undeveloped hygienic infrastructure where malnutrition of children aggravates rotavirus infections.

[Viral etiology of aseptic lymphocytic meningitis. Twenty-four cases seen over a nine-year period (author's transl)]. / L'étiologie virale des méningites lymphocytaires aiguës bénignes. A propos de vingt-quatre cas recueillis en neuf ans.

Among 208 cases of aseptic lymphocytic meningitis seen over a nine-year period, 24 were diagnosed as viral infections. Diagnosis was established by both isolation of the virus from one or several specimens (feces, pharyngeal mucus, CSF) and significant rise in specific antibody titres. The usual clinical and epidemiological characteristics of these benign infections were demonstrated in our series: prevalence in males; recrudescence in summer; infectious syndrome associated with an unequivocal, though moderately severe, meningeal syndrome, and occasionally with various visceral manifestations (exanthema, pharyngitis, acute respiratory disease, myalgia); clear CSF usually with pleiocytosis (relative but not absolute predominance of lymphocytes) and normal chemical findings. All the cases in our series were due to enteroviruses, Echo or coxsackie. Isolation of a poliovirus (type III) in one case deserves mention. Cases where clinical examination led to unequivocal diagnosis of mumps or herpes zoster were not included in our study.

[Anti-BCG antibody titers in healthy and leprous Africans. Value of an indirect immunoperoxidase test]. / Titrage d'anticorps anti-BCG chez des Africains sains et lépreux. Intérêt d'un test indirect à l'immuno-peroxydase.

An immunoperoxidase reaction was used for the titration of immunoglobulins G and M antibodies to BCG in 171 leprosy patients from Dakar. The results show mean titers decreasing from lepromatous to tuberculoid cases. The antibody profiles of some clinical forms such as reverse reactions, erythema nodosum leprosum are discussed. This test associated to the Mitsuda reaction, bacteriology and histology should allow an easier classification of the borderline forms. The main advantages of the technique are simplicity, speed, low cost and the easy availability of the BCG. These qualities are essential in endemic zone.

[Detection of human rotaviruses in faeces : comparison of five methods]. / Détection des rotavirus humains dans les selles : Comparaison de cinq techniques.

The authors have tested 118 stools by five techniques used for the detection of rotaviruses in human faeces : electron microscopy, latex agglutination (Slidex Rota-kit : BioMérieux ; Rotalex : Orion Diagnostica) and ELISA (Enzygnost : Behring ; Bio-Enza-Bead : Bionetics). Reproducibility and specificity for all techniques were satisfactory. Comparison of the methods showed Enzygnost to be the most sensitive (89 %), followed by the two agglutination tests, then electron microscopy and least sensitive the Bio-Enza-Bead (56 %). For large - scale screening of faeces, it appeared that the latex agglutination test were preferable for reasons of simplicity, speed and cost.

[Use of the Bactec TB 460 method for the bacteriological diagnosis of tuberculosis. Results of a multicenter study]. / Utilisation de la méthode Bactec TB460 pour le diagnostic bactériologique de la tuberculose. Résultats d'une étude multicentrique.

Isolation of Mycobacteria on Loewenstein-Jensen medium lasts many weeks. The use of Radiometric method (Bactec TB 460) reduces the delays. Results of 79,064 cultures are reported from a multicentric study associating 16 laboratories. The average was 4.8% of positivity and 2.51% of contamination. The comparison of the results with conventional method previously obtained shows that radiometric method is more sensitive and contaminations are less numerous. Concerning hemocultures the Bactec method is very usefull. Among 11,277 tests performed 907 were positive (8.04%). Mycobacterium avium was identified in 89% of the cases. Identification test utilizes Biochemical and NAP tests, but also more and more Nucleic probes. The antibiotic sensitivity is performed in five days. The mean delay of analysis is about 25 days, lessening by half the conventional method delays. Nevertheless, Bactec method has the following inconveniences: syringe inoculation, use of radiolabelled products, expensive cost.