Treatment outcome of patients with synchronous oligometastatic non-small cell lung cancer in the immunotherapy era: Analysis of a real-life intention-to-treat population.

The standard first-line treatment for non-oncogene driven metastatic non-small cell lung cancer (NSCLC) is an immune checkpoint inhibitor (ICI) based strategy. Although guidelines increasingly advise adding local radical treatment (LRT) to patients with synchronous oligometastatic (sOMD) NSCLC responding to systemic therapy, this recommendation is based on the studies without ICI. Furthermore, the majority of published oligometastatic studies were not on an intention-to-treat basis, resulting in selection bias. Moreover, staging Positron Emission Tomography-Computed Tomography (PET-CT) and brain imaging were often not mandatory and definitions of oligometastatic were heterogeneous. Therefore, this study focused on a single centre retrospective series, including all adequately staged patients with sOMD NSCLC according to the European Organisation for Research and Treatment of Cancer definition (maximum of 5 metastases in 3 organs) that were treated with induction (chemo)-ICI and compared outcomes to those treated with chemotherapy only, with and without LRT. The primary end-points were median progression-free survival (PFS) and overall survival (OS) for patients treated with induction (chemo)-ICI versus chemotherapy. Out of 68 included patients, 38 (56%) eventually received LRT. With a median follow-up of 26.7 months, the median PFS was 19.0 months for (chemo)-ICI (n = 18) versus 6.8 for chemotherapy-only (n = 50) (HR 0.5, p = 0.03), the median OS was 19.3 versus 15.7 months, respectively (HR 0.8, p = 0.4). In patients having received LRT, median PFS was 19.0 months for (chemo)-ICI versus 8.3 for chemotherapy-only (HR 0.6, p = 0.2). In conclusion, an ICI-based systemic treatment is feasible and may result in superior survival outcomes. This should be investigated in prospective trials. Strategies to improve response rates to systemic treatment are also needed.

A comparison of invasive versus noninvasive full-time mechanical ventilation in Duchenne muscular dystrophy.

The aim of this study was to compare morbidity and causes of death in a series of 42 Duchenne patients receiving full-time mechanical ventilation either by tracheostomy (TR, n = 16 or by noninvasive methods (noninvasive ventilation [NIV], n = 26). At inclusion for a 5-year observation period (2002-2006), TR and NIV patients were 32.7 and 27 years old, respectively. A program of follow-up with similar ventilation devices, techniques of respiratory physiotherapy, and drugs was applied to all the patients [TR + NIV]. Ages and respiratory characteristics at death and causes of death were comparable between groups. Morbidity was worse in TR compared with NIV patients; mucus hypersecretion and tracheal injuries were more frequent, whereas loss of weight and need for gastric feeding appeared less frequent in the TR group. Because noninvasive techniques avoid the severe complications associated with TR with comparable mortality, the authors support the use of noninvasive interfaces as default choice when assisted ventilation is required for daytime use.

Diurnal ventilation via mouthpiece: survival in end-stage Duchenne patients.

The present study aimed to assess the impact of diurnal mouthpiece intermittent positive pressure ventilation (MIPPV) as the extension of the nasal intermittent positive pressure ventilation (NIPPV) in Duchenne muscular dystrophy (DMD). In total, 42 DMD patients aged 15-33 yrs, normocapnic at night with NIPPV and receiving MIPPV since end-diurnal hypercapnia, were studied. Transcutaneous CO2 tension (Pt,CO2) was prospectively monitored at the end of the day, before and after MIPPV initiation. Vital capacity (VC), breathing pattern and maximal inspiratory strength were measured. Patients were asked to score the presence (1 point) or absence (0 point) of seven respiratory-linked symptoms before and after MIPPV establishment. Survival rates reached 88, 77, 58 and 51% after 1, 3, 5 and 7 yrs, respectively. The mean survival rate was 31 yrs. VC stabilised during 5 yrs with MIPPV. Symptom scores significantly decreased and Pt,CO2 normalised during the day (8.17 +/- 2.22 to 5.78 +/- 0.73 kPa). No accident and minor side-effects were observed in this 184 cumulated patient-yrs study. In conclusion, daytime mouthpiece ventilation is safe, prolongs survival and stabilises vital capacity in Duchenne muscular dystrophy patients. It is recommended on the condition that patients are equipped with a self-supporting harness.

Lethal oxidative damage to human immunodeficiency virus by human recombinant myeloperoxidase.

Human recombinant myeloperoxidase was evaluated in a cell-free system for its inactivation properties on the replication of human immunodeficiency virus, HTLV-IIIB. In the presence of a hydrogen peroxide generating system (glucose and glucose oxidase) and sodium thiocyanate, the recombinant enzyme inhibited virus-induced syncytium formation and viral replication without causing any cytopathic effects on SupT1 reporter cells. In addition, U937 monocytoid cells, chronically infected with HIV1, were exposed to recombinant myeloperoxidase (10 U/ml) and monitored during 48 h for the accumulation of intracellular p24 viral antigen. Under these conditions, the recombinant enzyme significantly reduced intracellular viral replication without affecting cell viability.

Seroepidemiological study on sexually transmitted diseases and hepatitis B in African promiscuous heterosexuals in relation to HTLV-III infection.

A seroepidemiological study was performed on HTLV-III, T. pallidum, C. trachomatis and Hepatitis B virus (HBV), in Butare, Rwanda, among 33 female prostitutes, 25 male customers of prostitutes, and 60 male and female controls. As compared with female controls the prostitutes had a higher prevalence of antibodies to HTLV-III (29/33 versus 4/33, p less than 0.001), T. pallidum (TPHA: 27/33 versus 6/33, p less than 0.001; RPR: 19/33 versus 2/33, p less than 0.001; FTA-Abs: 27/33 versus 5/33, p less than 0.001) and C. trachomatis (IgG IF: 31/33 versus 13/33, p less than 0.001). HBV serological markers were more often detected in the prostitutes than in the female controls (31/33 versus 18/33, p less than 0.001) although HBs antigen carriage rate was similar in both groups. As compared with male controls, the male customers of prostitutes had more frequently detectable antibodies to HTLV-III (7/25 versus 2/27, p = 0.05), and a positive RPR (10/25 versus 1/27, p less than 0.01). Among the 118 individuals studied, odds ratios and trend analysis disclosed a significant association between HTLV-III seropositivity and a positive TPHA, RPR, FTA-Abs, Chlamydia IgG IF test and serological markers to HBV. No association was found between HTLV-III seropositivity and HBs Ag carriage. This study suggests that HTLV-III has to be considered as an infectious agent transmitted among promiscuous Central African heterosexuals by sexual contact and/or parenteral contact with unsterile needles used for STD treatments.

Serum sensitivity of strains isolated and antibodies against O antigen in gram-negative bacteraemia.

The sensitivity of blood culture isolates to the bactericidal activity of normal human serum (NHS) has been studied in 101 patients with gram-negative sepsis. These results were compared with clinical status and outcome, and to the presence of specific IgG or IgM antibodies to O antigens of bacteraemic strains in autologous serum. 23% of the strains were markedly resistant, 27% markedly sensitive and 50% intermediately sensitive to the bactericidal activity of NHS. Shock or death occurred more frequently in immunocompromised patients and those infected with serum-resistant strains. IgG antibody titres to O antigens were significantly lower in patients with serum-resistant organisms regardless of their immune status. Resistance to natural bactericidal antibodies and low immunogenicity of the infecting organism, plus immunodeficiency in the host, may account for apparent increased virulence of some gram-negative bacilli.

Cytotoxic effect of a reverse transcriptase inhibitor, AF/ABDP cis, on ovaries of young Xenopus laevis--ultrastructural and autoradiographic study.

Observations with the light and electron microscopes showed that a reverse transcriptase inhibitor, AF/ABDP cis which is a rifampicin derivative, had a toxic effect on ovaries of young Xenopus laevis. It induced mitochondrial damage in all observed cells and marked alteration of the ultrastructure of nucleus of the pachytene oocyte. Light autoradiography showed that AF/ABDP cis caused wide variation in nuclear labelling with [3H] thymidine from one pachytene oocyte to another. Somatic cells were more uniformly labelled. These results are discussed in relation to the interpretation experiments upon eucaryote cells in which this drug is used as a reverse transcriptase inhibitor.