Children with Kawasaki disease or Kawasaki-like syndrome (MIS-C/PIMS) at the time of COVID-19: are they all the same? Case series and literature review.

Since the coronavirus disease 2019 (COVID-19) outbreak started, children have been considered marginally involved compared to adults, with a quite significant percentage of asymptomatic carriers. Very recently, an overwhelming inflammatory activation, which shares clinical similarities with Kawasaki disease (KD), has been described in children exposed to COVID-19. We report three KD-like cases that occurred during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a highly affected area of Northern Italy. The clinical presentation was characterized by the presence of unremitting fever, diarrhea and elevated inflammatory markers. Case #1 and Case #2 occurred one week apart and shared other clinical features: laboratory tests confirmed COVID-19 exposure and high inflammatory activation with myocardial involvement. Case #3 followed a more typical pattern for KD. Interestingly, this patient showed lower levels of procalcitonin, C-reactive protein, D-dimers, and ferritin compared to the other two cases, whereas platelet count was higher. We hypothesize that SARS-CoV-2 might act in children as a trigger, either inducing a classical KD phenotype or causing a systemic inflammatory response leading to a severe KD-like phenotype, eventually characterized by myocardial impairment. We think that bringing these cases and their differences to the attention of the rheumatology community during the COVID-19 pandemic will be beneficial in order to highlight the importance of early diagnosis and to increase awareness of this new phenomenon.

Chromosome 22 marker in a child with Duane syndrome and urogenital abnormalities.

The nature and the origin of de novo small marker chromosome found at prenatal diagnosis were determined by fluorescence in situ hybridization (FISH) using chromosome centromere-specific probes and by chromosome in situ suppression (CISS) using chromosome specific libraries. The small marker was characterized as being derived from chromosome 22. The fetus which exhibited a minichromosome had kidney malformations and after birth showed clinical features consistent with the Duane anomaly. One previous case with Duane anomaly and abnormalities of urogenital tract associated to a bisatellitated marker derived from chromosome 22 was reported. These findings indicate that a gene or genes located in the region of chromosome 22pter-->q11 may be associated with the Duane anomaly and the development of the urogenital tract.

[Fontan's operation: results, immediate and long-term postoperative complications]. / Intervento di Fontan. Risultati, complicanze postoperatorie e a distanza.

The Fontan operation and its modifications can be relatively safely performed in the treatment of many complex congenital heart diseases, such as univentricular heart and tricuspid atresia. The main postoperative complications following the Fontan procedure and the incremental risk factors involved in their development are investigated. Between January 1984 and January 1988 eleven patients (6 females and 5 males), ranging in age from 2 to 15 years (mean age: 7.3 +/- 3.7) and in weight from 10.8 to 50 Kg (mean weight 22.3 +/- 12.7) underwent the Fontan operation in our Department. No hospital death occurred. The mean postoperative stay in the Intensive Care Unit was 6.3 +/- 3.9 days. There were two surgical re-entries for the same patient: cardiac tamponade (the day of operation) and residual atrial septal defect (2 days following the operation). Eight patients had significant signs of venous stasis, with severe hepatomegaly and pleural effusion. The 11 patients discharged were followed-up for a period of between 3 and 48 months (mean follow-up: 26.4 +/- 18). There were 2 cases of recurrent pleural effusion, 10 to 15 days after discharge. One late death occurred 2 years after the Fontan procedure (massive pulmonary embolism after re-operation). Short and medium-term rate of complications is related to increased post-operative values of mean right atrial pressure (greater than 15 mmHg). Mean right atrial pressures greater than 15 mmHg appear to be correlated with Nakata index values less than 250 mm2/m2. The experience reviewed confirms the excellent results of the Fontan operation, as regards survival and functional recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and safety of flecainide in low-risk patients with chronic ventricular arrhythmias: a two-year follow-up.

The long-term efficacy and safety of flecainide (100 to 200 mg twice a day) were evaluated in 21 patients with high-grade, chronic ventricular arrhythmias who responded to and tolerated flecainide at a preliminary evaluation (200 mg, single oral dose). Antiarrhythmic response was evaluated at 3 days and 3, 6, 12, 18, and 24 months. The mean follow-up was 25 +/- 14 months (range 3 to 52). Four patients (19%) were excluded from efficacy analysis because of spontaneous decrease in baseline arrhythmia observed after 12 months of therapy. Effective arrhythmia suppression at both Holter monitoring and during exercise stress testing was maintained in 14 of 17 patients (82%). Mean frequency of premature ventricular contractions remained reduced by more than 95% throughout the follow-up. Five patients discontinued therapy between 3 and 18 months because of drug ineffectiveness (three patients, 18%) or side effects (two patients, 12%). In 12 patients (71%) long-term efficacy and tolerance were demonstrated. In no case was aggravation of arrhythmia or adverse cardiac effects observed. Side effects (5% to 29% of patients during follow-up) were usually minor and easily abolished by dosage reduction. In patients with chronic ventricular arrhythmias, flecainide maintained a favorable ratio between efficacy and side effects during a 2-year follow-up.

Multiple comparison of several antiarrhythmic agents by acute oral drug testing in patients with chronic ventricular arrhythmias.

This study addresses the question of the choice of treatment for the individual patient with chronic ventricular arrhythmias. Acute oral drug testing offers a pragmatic approach to the rapid selection of the drug with the best efficacy/side-effect ratio by allowing multiple comparisons within the same patient. Forty patients with chronic ventricular arrhythmias received a single oral dose of the following antiarrhythmic drugs: flecainide 200 mg, propafenone 450 mg, disopyramide 300 mg, mexiletine 400 mg, tocainide 800 mg, verapamil 160 mg, propranolol 120 mg. Criteria for efficacy were suppression of complex ventricular arrhythmias and a greater than 90% reduction in premature ventricular beats lasting for at least 2 h. An antiarrhythmic effect was achieved with each of the drugs in the following percentages of patients: flecainide 69.4%, propafenone 67.5%, disopyramide 54.8%, mexiletine 45.2%, tocainide 31.3%, verapamil 31.3%, propranolol 12.5%. In no case was worsening of arrhythmia observed. At the end of the acute testing phase, the drug that had proved most effective in each patient was administered at a full dosage for 72 h. A concordant response between the two phases was observed in 80% of patients and was as high as 89% when the analysis was limited to flecainide and propafenone. This study shows the feasibility and practical advantages for patient management of a multiple comparison of antiarrhythmic drugs by acute oral drug testing. It also provides, in a non-invasive cost-effective manner, unique insights into the complex relationship between drug characteristics, individual responses and clinical efficacy.

Antiarrhythmic efficacy of penticainide and comparison with disopyramide, flecainide, propafenone and mexiletine by acute oral drug testing.

The antiarrhythmic efficacy of a new class I agent, penticainide, was evaluated by acute oral drug testing and compared in the same patient population with the efficacy of disopyramide, flecainide, mexiletine and propafenone. Twenty-five patients with high-grade chronic ventricular arrhythmias entered the study. During acute oral drug testing, penticainide (7 mg/kg) was effective (more than 90% reduction in ventricular premature complexes and complete abolition of class 4A and 4B arrhythmias) in 17 of 25 subjects (68%). The mean plasma level of the drug at 90 minutes was 4.4 +/- 1.9 micrograms/ml; at the same time increases in the PQ interval (from 168 +/- 27 to 189 +/- 31 ms, p less than 0.0001) and QRS duration (from 89 +/- 14 to 96 +/- 18 ms, p less than 0.001) were observed. The QTc was slightly but not significantly shortened in the overall population; however, in the subgroup with a basally prolonged QTc (n = 8), a significant reduction was observed (from 456 +/- 8 to 440 +/- 18 ms, p less than 0.02). No adverse effects were reported. The antiarrhythmic efficacy of the other drugs tested in the same population was: disopyramide, 12 of 19 (63%); flecainide, 13 of 24 (54%); propafenone, 13 of 24 (54%); and mexiletine, 7 of 20 (35%). Penticainide appears to be a well-tolerated and effective compound of potential value for treatment of ventricular arrhythmias.

[Evaluation of flecainide in the therapy of chronic ventricular arrhythmia using the acute oral load method]. / Valutazione della flecainide nella terapia delle aritmie ventricolari croniche con il metodo del carico orale acuto.

The efficacy of the new class Ic anti-arrhythmic (aa) drug, Flecainide, has been evaluated in patients (pts) affected by frequent and/or severe chronic ventricular arrhythmias (VA), as assessed by 24 hours Holter monitoring and maximal exercise stress testing. The protocol consisted in a preliminary screening with multiple aa drugs (average 6.0 per pt) using the acute oral drug testing. The most effective drug was then given for 72 hours and 24 hours Holter monitoring and exercise stress testing repeated; if the efficacy was confirmed, chronic treatment was initiated and control visits were repeated after 3, 6 and 12 months. The study population consisted of 27 pts; 22 (81%) were in Lown class 4A (18%) or 4B (63%). Eight pts (30%) had a previous (greater than 1 year) myocardial infarction, while in 14 (52%) no evidence of cardiac disease was found. During acute oral drug testing a positive response (reduction of PVC's greater than 90% and abolition of grades 4A and 4B) was obtained with Flecainide, 200 mg, in 20 pts (74%). In 6 pts (22%) no effect was observed, while a possible proarrhythmic effect was observed in 1 pt (4%). Eighteen pts entered the second phase of the study with an average dose of Flecainide of 175 mg b.i.d. In 83% of the pts there was a positive concordance between the acute oral testing and the 72 hours treatment, as in 15 out of 18 pts grades 4A and 4B were totally abolished and the mean frequency of PVC's was reduced by 99%. In 3 pts (17%) no response was observed. Flecainide increased significantly PR (37 msec), QRS (20 msec) and QTc (28 msec). The plasma levels attained with chronic therapy (846 ng/ml) were higher than those achieved with the acute oral testing (372 ng/ml). Mild side effects (dizziness, tremor and headache) were observed in 33% of the pts and were all eliminated by a 100 mg reduction in Flecainide dose. Fifteen pts entered the third phase (long term treatment): in this group there was a 93.3% correlation with phase two, as in 14 out of 15 pts there was a complete abolition of grade 4B arrhythmias, a 98.8% reduction of couplets and a reduction in the number of PVC's greater than 85%. This study shows that Flecainide is a quite powerful aa drug with modest side effects. Its efficacy against chronic VA is high, also when compared to the most effective and available aa drugs.(ABSTRACT TRUNCATED AT 400 WORDS)