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.

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.

[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.

[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.

Influenza epidemic among a community of elderly people in spite of vaccination.

An outbreak of influenza occurred in a nursing home of 81 vaccinated elderly people. The clinical attack rate was 73%. The responsibility of an A/H3N2 strain was proved in 12 patients and 2 staff members of the 15 investigated persons. The vaccine was effective in reducing mortality but not morbidity. An antigenic drift between the wild and the vaccine strains was involved in the inefficiency of the vaccination.

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.

[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.

An epidemic of respiratory syncytial virus in elderly people: clinical and serological findings.

In 1984-1985, an outbreak of respiratory syncytial virus (RSV) infection occurred in two geriatric wards. Among 68 patients (mean age +/- SD = 82.5 +/- 12.5 with respiratory signs, 52 had signs caused by RSV infection. Among all patients, the clinical and serological attack rates were 61.2% and 75.0%, respectively. The most frequent clinical presentation was intensive coughing (96.1%) and fever (96.1%) associated with expectorate (63.5%). The duration of the respiratory symptoms was 5 to 7 days. The disease gradually resolved, although in eight (15.4%) patients complications occurred. For periods of up to 1 year after infection, 172 sera were obtained and tested by complement fixation test (CFT), fluorescent assays for titrating specific IgG, IgA, and IgM, and Western blotting. Specific IgM appeared in six (11.5%) of the infected patients and peaked 2 to 6 months after infection, and there was no significant correlation with severity of clinical symptoms. However, higher peak G and A antibody responses were observed in persons with rales (CFT: P = 0.008; IgG: P = 0.042; IgA: P = 0.020), cough (IgG: P = 0.034), sputum (IgG: P = 0.030), dyspnea (CFT: P = 0.024), conjunctivitis (CFT: P = 0.025), and bronchitis (CFT: P = 0.018). The temporal patterns of IgA and CFT results were found to be similar, whereas IgG peaked later, i.e., between 2 and 6 months. The patients with the most severe symptoms had the highest antibody titers obtained by conventional tests and by Western blots. Thus, RSV can be an epidemic pathogen among elderly persons, although this illness is usually mild.

[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.

[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.