Management of immune-related adverse events resulting from immune checkpoint blockade

Introduction: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient’s treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg.

Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs.

Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.     

Catecholaminergic polymorphic ventricular tachycardia in a child: an often unrecognized diagnosis]

Catecholaminergic polymorphic ventricular tachycardia is important to be diagnosed as an underlying disease in children with syncope and normal heart, because of its poor prognosis. CASE REPORT: A 3-year-old boy was referred for stress and emotion induced syncope. Primary ventricular arrhythmia, consisting of salvos of bidirectional ventricular tachycardia, was reproducibly induced by physical exertion. The syncopal events and severe arrhythmia disappeared with beta-blocking therapy. CONCLUSION: Despite its rare occurrence, catecholaminergic polymorphic ventricular tachycardia is an important cause of stress and emotion induced syncope and sudden death in children.     

Primary open-angle glaucoma. Effects of an eyedrop combining timolol and pilocarpine on the ocular pressure

In a limited group of open angle glaucoma patients treated twice daily with timoptol 0.5% and having by this treatment a mean intra-ocular pressure of 21-22 mmHg, the association of timoptol 0.5% with pilocarpine 2% respectively, lowered the intra-ocular pressure to an average of 17.8 mmHg and 16.6 mmHg after one and three weeks of continuous treatment. For this study, the patients have been divided into 3 groups: A group treated with timoptol 0.5% alone throughout the 49 days of the study. A group treated with timoptol 0.5%-pilocarpine 2% (timpilo 2) from day 21 to day 49. A final group treated with timoptol 0.5% until day 21 and then with timoptol 0.5%-pilocarpine 4% (timpilo 4) through out day 49. These patients stopped the treatment before the end of the study. Intra-ocular pressures were measured on days 0, 21 and 49. We found a higher drop of pressure (-4.8 mmHg) in the timpilo 2 group than in the timoptol 0.5% group (-1 mmHg) before instillation as well as 2 hours afterwards (-5.25 mmHg and -2 mmHg respectively). The secondary local effects were due to miotics agents. The secondary systemic effects were those inherent to beta-blockers. These results are comparable with a multicentric study of 220 patients, therefore statistically significant.     

Differential anti-influenza activity among allelic variants at the Sus scrofa Mx1 locus.

A promising way to oppose infectious challenges would be to improve the resistance of the target species through genetic selection. Theoretically, a candidate gene is available against influenza viruses since a resistance trait was fortuitously discovered in the A2G mouse strain. This trait was demonstrated to be correlated with the expression of a specific isoform of the type I interferon (IFN)-dependent protein MX, an isoform coded by a specific allele at the mouse Mx1 locus. Two allelic polymorphisms were described recently in the Sus scrofa homologous gene. In this study, the frequencies and distribution of both alleles were evaluated among European domestic pig and wild boar populations by PCR-RFLP, and the anti-influenza activity conferred by both MX1 isoforms was evaluated in vitro using transfection of Vero cells followed by flow cytometric determination of the fraction of influenza virus-infected cells among MX-producing and MX-nonproducing cell populations. A significant difference in the anti-influenza activity brought by the two MX1 isoforms was demonstrated, which suggests that a significant improvement of innate resistance of pigs by genetic selection might be feasible provided the differences found here in vitro are epidemiologically relevant in vivo.     

Manifestation pseudo-tumorale d’une métallose sur prothèse de hanche –à propos d’un cas

Summary. A pseudo-tumour due to metallosis is described in association with an iso-elastic hip replacement. This is a relatively rare lesion which may be difficult to diagnose. Scintigraphy and radiography may be helpful in distinguishing the lesion from a primary or secondary neoplasm, but the presence of osteolysis adjacent to the prosthesis will suggest the true nature of the lesion.

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Résumé. Les auteurs rapportent un cas de manifestation pseudo-tumorale d’une métallose sur prothèse de hanche de type iso-élastique. Il s’agit d’une lésion relativement rare qui peut parfois avoir un aspect inquiétant. Elle nécessite un bilan radiologique et scintigraphique pour éliminer une tumeur primitive ou secondaire, mais le diagnostic est facilement évoqué devant une ostéolyse au contact de la prothèse. Nous décrirons notre démarche diagnostique et thérapeutique dans ce cas.

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Accepted: 29 February 1996     

Evaluation of ciprofloxacin versus amoxicillin + clavulanic acid or erythromycin for the empiric treatment of community-acquired pneumonia

For the empiric management of community-acquired pneumonia, ciprofloxacin (750 mg b.i.d.) was compared with two antibiotics frequently used in this indication, i.e., amoxicillin + clavulanic acid and erythromycin. One hundred and forty-two patients were randomized in this prospective study. Among them, the 63 patients with bacteriologically documented disease were evaluated. Clinical recovery was achieved in 73.3% of patients in the ciprofloxacin group (22/30) versus 81.8% of patients in the amoxicillin + clavulanic acid or erythromycin group (27/33) (non-significant difference). Clinical failures seen with ciprofloxacin were found to be correlated with recovery of Streptococcus pneumoniae. Ciprofloxacin is effective in pneumonia but should be used only in cases where Streptococcus pneumoniae can be excluded as the causative agent.     

Left lower lobe transplantation during a bilateral single lung transplantation (pulmonary lobe transplantation).

An isolated left lower lobe was used as a left graft, during a bilateral single lung transplantation procedure, in a patient with infected fibrosis. This technique is suitable for patients with small lung volume (especially cystic fibrosis) or asymmetric retraction.     

L’impossible écart entre représentations du corps malade et représentation de soi

The present study focuses on deepening our understanding, from a clinical perspective, of the psychological processes of cancer patients. Through a qualitative analysis of speech, the authors investigate the major organizing and structuring factors of the cancer experience: the lived body, acting in the world, the bond with others, temporal experience and the “other self”. This breakdown of factors, however, proves to be an inadequate approach. Only a clinical approach can ensure the patient receives the focused listening that is key.