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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.

Locally advanced and metastatic cutaneous squamous cell carcinoma (cSCC) of the skin is a rare entity and with a poor prognosis. Although less than 5% of patients with squamous carcinoma develop metastases or relapses locally after surgical removal, cSCC is difficult to treat. It tends to develop especially in elderly, frail or patients with important comorbidities and therefore not suitable for receiving aggressive treatments. Traditionally, platinum-based therapy has been considered a conventional option, but not feasible in elderly patients. The high number of advanced cSCC mutations constitutes the rationale for a systemic immunotherapy approach that can represent a turning point for these patients. Furthermore, it is necessary that more professional figures (dermatologist, oncologist, surgeon, radiotherapist, geriatrician) work in a multidisciplinary environment so that these patients can be better managed during their care path.

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.

Methods for the analysis of the oxide-silicon interface were compared for their ability to reveal metal segregation at the interface and organic contamination. The impact of these contaminations on surface recombination velocity measurements, on capacitance vs. voltage, conductance vs. voltage and capacitance vs. time measurements and on MOS-DLTS spectra was studied. Niobium-contaminated wafers were used as an example of metal surface segregation, because it was previously shown that niobium is prone to surface segregation. Interface state density measurements obtained by the conductance method showed a limited impact of niobium implantation. Vice versa significant effects were found in MOS-DLTS spectra. For what concerns organic contamination, MOS-DLTS showed the most significant effects from the point-of-view of the intrinsic properties of the silicon oxide - silicon interface, and GOI tests demonstrate a clear impact of the organic contamination on MOS capacitors oxide breakdown events.

In this paper niobium is characterized as a silicon contaminant. It is shown that niobium is a relatively slow diffuser, with an intermediate diffusivity between very slow diffusers such as molybdenum and fast diffusers such as iron. Niobium is found to be very effective as a recombination center, and in addition prone to surface segregation. In addition, niobium shows optical activation, but no thermal activation. Three deep levels are revealed in niobium contaminated silicon, plus an additional level observed in high contamination dose samples only. One of these levels is located very close to midgap, and consistently niobium was also found very effective in degrading the generation lifetime.

Patients with non metastatic squamous cell lung cancer were treated with radiotherapy (RT) plus lonidamine (LND) or placebo (PLAC), according to a randomized double-blind study design. Treatment with lonidamine 150 mg t.i.d. (27 patients) or placebo (23 patients) started 3 days before RT, lasted up to 7 months. Partial responses were observed in 14 and 6 patients respectively in the LND + RT and PLAC + RT groups. Statistical analysis of the survival curves showed no significant difference between the LND + RT (median 311 days) and PLAC + RT (median 193 days) groups. Stage III patients survived significantly longer (p less than 0.05) when treated with LND + RT (median 318 days) than with PLAC + RT (median 163 days). No synergistic toxic effects between radiation and LND were noted. To confirm these data a new and larger multicentric study is now in progress.

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.