Cutaneous toxicities in patients with melanoma receiving checkpoint inhibitor therapy: a retrospective review. The experience of a single large specialist institution.

Checkpoint inhibitor (CPI) therapy has significantly improved overall survival for metastatic melanoma, and is now approved for use in the adjuvant setting. Modulating the immune system is recognized to cause cutaneous immune-related adverse events (irAEs). We conducted a retrospective observational cohort study of adult patients with melanoma at our tertiary referral centre, who received CPI therapy from 2006 to March 2018. This is the single largest study of cutaneous irAEs occurring on CPI therapy in patients with melanoma to date and encompasses 12 years. The results showed that cutaneous toxicity occurs in 24% of patients but is generally manageable, with < 5% patients discontinuing treatment.

[Predictive value of various echocardiographic parameters of systolic and diastolic function in the development of congestive heart failure after infarction]. / Valore predittivo di alcuni parametri ecocardiografici di funzione sistolica e diastolica nello sviluppo di insufficienza cardiaca congestizia nel postinfarto.

To evaluate the predictive value of systolic and diastolic left ventricular (LV) function parameters, in the development of congestive heart failure (CHF) after acute myocardial infarction (AMI), 48 patients (mean age 56.2 +/- 10.4 years) were studied with two-dimensional and Doppler echocardiography (2D echo) in the acute phase (36 +/- 12 hours) and after 6 months of follow-up. The following parameters have been evaluated: LV wall motion score-index; peak velocity of early diastolic filling (E); peak velocity of filling during atrial systole (A); the ratio A/E; percent of LV filling contributed by atrial systole (A%). During follow-up 10 patients (Group B; 21%) developed symptoms and/or signs of CHF, while 38 patients (Group A; 79%) did not. In the patients who developed CHF 2D echo showed a depressed contractile function (mean value of wall motion score-index 3.08 +/- 0.45 versus 3.53 +/- 0.32 of Group A; p < 0.001) and a marked impairment of filling during atrial systole: A/E = 1.89 +/- 0.80 versus 1.07 +/- 0.35 (p < 0.001); A% = 52.2 +/- 9.9 versus 39.1 +/- 8.4 (p < 0.001). The multivariate analysis showed that the ratio A/E, A% and the wall motion score-index are the only variables that may predict the development of CHF. This capacity has been confirmed also considering the cut-point as conditional variables (A/E > 1.4; A% > 45%; score-index < 3.1). Our results demonstrate that a combined evaluation by 2D echo of systolic and diastolic LV function parameters allowed a better stratification of patients at risk of developing CHF after an AMI.

Clinical significance of small left-to-right shunts after percutaneous mitral valvuloplasty.

Left-to-right shunt after percutaneous mitral valvuloplasty was evaluated by contrast echocardiography in 29 patients at 24 hours and at 1, 3, 6, and 9 months after the procedure. The patients were divided into two groups: in group A (13 patients) the double-balloon technique was used; in group B (16 patients) the Inoue single-balloon technique was used. The two groups were comparable in terms of age, gender, and mitral valve area before and after percutaneous mitral valvuloplasty. A left-to-right shunt was detected in all patients 24 hours after the procedure. At 1 month follow-up the shunt was present in 12 patients of group A (92%) and in 13 of group B (81%) with a statistically significant difference (p < 0.001). At 3 months the values were 7 (54%) in group A and 6 (37.5%) in group B (p < 0.05); at 6 months the values were 3 (23%) in group A and 3 (19%) in group B (NS). At 9 months a left-to-right shunt was no longer detectable in any of the patients in either group. The disappearance of the shunt could be related to a healing process of the atrial septal injury that occurs within a few months after percutaneous mitral valvuloplasty. This process seems to be more rapid in group B patients, probably because of the smaller lesion that is produced in the atrial septum by the passage of the Inoue balloon.