[Immune-related pneumonitis: A differential diagnosis of SARS-CoV-2 pneumonia]. / Pneumopathie immuno-induite : un diagnostic différentiel de la pneumopathie à SARS-CoV-2.

INTRODUCTION: Immune checkpoint inhibitors have revolutionized the management of many cancers and achieved efficacy and durable response for some patients, including those with advanced cancers. However, immunotherapy is associated with side effects caused by the infiltration of immune cells into normal tissues, which can lead to disproportionate dysimmune reactions. While mostly of moderate intensity, these side effects can affect any organ, including the lung, the site of occasionally life-threatening interstitial lung disease. Their presentation can be similar to that of infectious pneumonia (COVID-19). OBSERVATIONS: We report the cases of 3 patients who presented between March and May 2020 with severe pulmonary toxicities secondary to immunotherapy, which led to with an initial hypothesis of SARS-CoV-2 pneumonia. After extensive investigations, the diagnosis of pulmonary toxicity to immunotherapy was given, and the clinical and radiological course following the initiation of corticosteroid therapy was favorable. CONCLUSION: Pulmonary toxicity secondary to immunotherapy remains a rare but potentially life-threatening side effect. The diagnostic approach requires the elimination of several differential diagnoses (infectious process, tumor progression, other etiologies of interstitial lung disease). This adverse event is reversible and evolution after initiation of corticosteroid therapy is usually favorable.

Prevalence of Haemophilus influenzae with alteration of PBP 3 sequence over a 1-year period in a French hospital: focus on a clinical failure after ceftriaxone treatment.

Among 547 Haemophilus influenzae isolates recovered in our center, 45 displayed a phenotype of loss of PBP 3 affinity (8.2%). Two isolates with 6 substitutions in PBP 3 showed decreased susceptibility to third-generation cephalosporins. Clinical data revealed clinical failure after ceftriaxone treatment in a context of bronchitis in a patient with pulmonary sarcoidosis.

TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood.

After invading red blood cells (RBCs), Plasmodium falciparum (Pf) can export its own proteins to the host membrane and activate endogenous channels that are present in the membrane of RBCs. This transport pathway involves the Voltage Dependent Anion Channel (VDAC). Moreover, ligands of the VDAC partner TranSlocator PrOtein (TSPO) were demonstrated to inhibit the growth of the parasite. We studied the expression of TSPO and VDAC isoforms in late erythroid precursors, examined the presence of these proteins in membranes of non-infected and infected human RBCs, and evaluated the efficiency of TSPO ligands in inhibiting plasmodium growth, transporting the haem analogue Zn-protoporphyrin-IX (ZnPPIX) and enhancing the accumulation of reactive oxygen species (ROS). TSPO and VDAC isoforms are differentially expressed on erythroid cells in late differentiation states. TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection. TSPO ligands dose-dependently inhibited parasite growth, and this inhibition was correlated to ZnPPIX uptake and ROS accumulation in the infected RBCs. Our results demonstrate that TSPO ligands can induce Pf death by increasing the uptake of porphyrins through a TSPO2-VDAC complex, which leads to an accumulation of ROS.

Effects of the multiple risk factor intervention trial smoking cessation program on pulmonary function. A randomized controlled trial.

To determine whether the decline in pulmonary function in smokers is modified by stop-smoking intervention, a randomized controlled study (the Multiple Risk Factor Intervention Trial) was done comparing participants in a special intervention group that included an intensive smoking cessation program with those assigned to usual care. The subjects were 6,347 middle-aged male smokers who had serial measurements of pulmonary function--principally the forced expiratory volume in 1 second (FEV1)--during 6 to 7 years of follow-up. No overall differences were detected in the rate of loss of FEV1 in the two groups. The use of beta-blockers, which had detrimental effects on FEV1, was significantly more common in the intervention group. Among nonusers of beta-blockers, heavy smokers lost FEV1 at a rate about 11 ml per year slower in the intervention group than in the control group (2P = .09) and ended the trial with an FEV1 about 90 ml higher (2P = .05). These results support the inference from observational studies that smoking cessation has a beneficial effect on pulmonary function in heavy smokers.

The effects of underrecorded forced expirations on spirometric lung function indexes.

A problem with short recorded lengths of expiration, encountered in a large heart attack intervention trial, illustrates the importance of standardization and training in spirometric lung function testing. At baseline, half of the trial's clinical centers had mean FVC values that were between 500 and 1,100 ml below those predicted for these centers. To quantify the effects of underrecorded forced expirations on the FVC, the FEV1/FVC%, the FEF70-80%, the FEF 25-75%, and the FEF45-55%, a study of 80 complete spirograms of good quality was undertaken. The findings were that short lengths of expiration cause underrecording of the FVC, inflating all of the examined FVC-dependent spirometric indexes. The inflation was fairly uniform across all obstructions for the forced expiratory flow rates, but it increased markedly with level of obstruction for the FEV1/FVC%. Virtually no subjects exhibited low values of these spirometric indexes after 3 s of expiration, and the number of subjects with low values was still substantially underestimated after 6 s of expiration. Whereas 18 (23%) of the subjects had FEV1/FVC% greater than or equal to 80% and 21 (26%) had ratios less than or equal to 69% based on complete expiration, 60 (75%) of the subjects had ratios greater than or equal to 80% and only 2 (3%) had ratios less than or equal to 69%, after 3 s of expiration. Even after 6 s, 26 subjects (33%) had ratios greater than or equal to 80%, and only 10 (13%) had ratios less than or equal to 69%. Therefore, completely recorded expirations are essential for accurate measurement of the FVC-dependent spirometric indexes.