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Immune-related myasthenia gravis is a rare, disabling, and potentially fatal adverse event of immune checkpoint inhibitor treatment. It is important to identify and manage it promptly. We present two cases of immune-related de novo myasthenia gravis observed at the Modena Cancer Center in two elderly patients treated with two anti-PD-1 monoclonal antibodies: cemiplimab and nivolumab.

Lurbinectedin is responsible for DNA recognition and binding, producing double-strand DNA (dsDNA) breaks thus resulting in apoptosis. Sensitivity to lurbinectedin is linked to the nucleotide excision repair (NER) system. Furthermore, irinotecan, a topoisomerase I inhibitor, provokes dsDNA breaks that could be reinforced abrogating the NER system using lurbinectedin. BRCA-mutated patients, already treated with platinum-derived drugs, who suffered DNA damage, cannot repair the breaks due to lurbinectedin interaction, whereas irinotecan provokes a dsDNA break that promotes synthetic lethality. This article describes an exceptional response to lurbinectedin alone followed by the association with irinotecan in a BRCA-mutated platinum-resistant ovarian cancer patient. A 44-year-old BRCA1-mutated ovarian cancer patient was treated in sixth line with lurbinectedin and irinotecan with a time to further progression (TTFP) equal to 8 months. In our case, the association with irinotecan overcame the resistance to lurbinectedin alone. In conclusion, lurbinectedin and irinotecan demonstrated a promising response in platinum-resistant patients. However, further studies should be conducted to validate our findings and future trials will be important to further define the clinical utility of lurbinectedin.

Introduction Immunotherapy dramatically changed history of melanoma patients with a clinical benefit never seen before. Nevertheless, severe and unexpected adverse effects can occur, fortunately rarely. Case presentation We reported the case of a 75-year-old male patient affected by metastatic melanoma who developed myocarditis and acute rhabdomyolysis with secondary diaphragmatic dysfunction and consequent pulmonary restrictive syndrome after Nivolumab monotherapy. Blood tests and ultrasonography of the diaphragm revealing left hypokinesis suggested a Nivolumab-related rhabdomyolysis, as an immune-mediated adverse event. The rhabdomylolysis involved the diaphragm with consequent diaphragmatic weakness and respiratory distress. Mangement & outcome The patient had a slow but slight and progressive improvement of symptoms and vital signs post-treatment with high-dose corticosteroids. Discussion With this case report, we want to highlight the importance of rapid recognition and treatment of rare and unexpected, but potential serious immune-related adverse events. These events might happen despite the remarkable clinical benefits of immune checkpoint inhibitors. We do not know which patients will benefit from these therapies and why, when and in which cases adverse event will occur: we must not lower our attention.

Given three measurable functions V r ≥ 0 , K r > 0 and Q r ≥ 0 , r > 0 , we consider the bilaplacian equation Δ 2 u + V ( | x | ) u = K ( | x | ) f ( u ) + Q ( | x | ) in R N and we find radial solutions thanks to compact embeddings of radial spaces of Sobolev functions into sum of weighted Lebesgue spaces.

Rationale: Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited. Objectives: To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death). Methods: In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy. Results: We collected data on demographic and clinical characteristics, ventilatory management, and patient outcomes. Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (PaO2)/fraction of inspired oxygen (Fi O2) ratio 60% and close to 75% in full-treatment patients. C-reactive protein, PaO2/Fi O2, and platelet counts were independently associated with increased risk of NIV failure. Clinical trial registered with ClinicalTrials.gov (NCT04382235).

Survey of the current state of public health emergency management teaching in italian school of specializzation in hygiene and preventive medicine among medical residentes

Aim: This observational study investigates the effectiveness and safety of dabrafenib/trametinib combination in patients with metastatic melanoma. Patients & methods: Seventy-six patients treated with dabrafenib/trametinib (150 mg twice daily/2 mg once daily) were included. Results: Median progression-free survival was 9 months (95% CI: 7–11) and median overall survival was 14 months (11–16); disease control rate was 72%. Nine patients (12%) experienced a complete response. Of these, seven presented one metastatic site, none had lung or CNS metastasis, and none had elevated baseline lactate dehydrogenase (LDH) levels. Overall, subgroup analysis for patients with adverse prognostic features led to similar results. No new safety signals were reported. Conclusion: Dabrafenib/trametinib combination can be effective and well-tolerated also in a heterogeneous ‘real life’ population comprising patients with adverse prognostic features.

Background/aim The mutational status of stage III and IV melanomas should be recognized in order to allow for targeted therapies. The aim of our study was the characterization of BRAF, NRAS and C-KIT melanoma patients, in order to define their optimal management. Patients and methods Between 1991 and 2015, 63 mutated melanoma patients were treated and monitored during their diagnostic and therapeutic management at a single institution. Results BRAF-mutated melanoma patients were the most common, representing 70% of the study population, while NRAS- and C-KIT-mutated melanoma represented 19% and 11% respectively. BRAF-mutated melanomas were mostly located at sites of intermittent sun exposure, and were associated with higher Breslow thickness and an increased number of mitosis. NRAS mutated melanoma were mainly observed in chronic sun-damaged areas and had a negative prognostic value, with shorter time to progression and a high incidence of central nervous system involvement. C-KIT mutated melanoma were located at acral and mucosal sites. Overall survival observed in the three groups of patients revealed wide differences. Conclusion BRAF, NRAS and C-KIT melanomas constitute distinct clinico-pathological entities. BRAF-mutated melanoma benefit from both anti-BRAF and anti-MEK targeted therapies while triple-negative melanomas could benefit from novel anti-CTLA-4 and anti-PD-L1 immunotherapeutic approaches.

The article is addressed to the European and Indian policy makers aiming in providing pragmatic recommendation for the bilateral governance of antimicrobial resistance. As noted by the UN Interagency Coordination Group, today drug resistance diseases cause at least 700 000 deaths globally per year. If tailored measures are procrastinated, antimicrobial resistance will lead to 10 million casualties per year. Drug resistant diseases are expected to become the first cause of death. In addition, antimicrobial resistance causes an unsustainable raise of the public expenditure in health, expanding its negative impact on the social and labour sphere – impacting harder developing societies and the poorer strata of the world population.