Body composition measures as a determinant of Alpelisib related toxicity.

BACKGROUND: Body composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity. METHODS: A retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, hospitalizations, time to treatment failure and overall survival. RESULTS: Sarcopenia was observed in half of the patients (n = 19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P = 0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P = 0.04) and hospitalizations (P = 0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity. CONCLUSION: Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to caution toxicity risk, allowing for personalized therapeutic observation and intervention.

Fractional Radiofrequency and Oral Isotretinoin-A Prospective Randomized Controlled Split-Face Trial Comparing Concurrent Versus Delayed Fractional Radiofrequency Treatment for Acne Scars.

BACKGROUND: Therapeutic dogma has been to treat acne scars no less than 6 months after isotretinoin (ITN) cessation. OBJECTIVE: To evaluate the safety and efficacy of fractional radiofrequency (FRF) in patients treated concurrently with ITN. METHODS: We conducted a prospective randomized control 3-arm comparative trial to evaluate the treatment of acne scars. Patients received one of three treatment options: (A) ITN and FRF concurrent treatment, (B) ITN monotherapy, and (C) FRF 6 months post-ITN treatment. Patients in the FRF cohorts received three monthly sessions. Patients were followed for adverse effects up to 6-9 months post-FRF treatment. Final cosmesis was scored by three independent dermatologists using two scales: the Echelle d'Evaluation Clinique des Cicatrices d'Acne (ECCA) and an internal 5-point investigator's scale, indicating the percentage of improvement. Subjective analyses by patients were also assessed. RESULTS: Objective and subjective analyses revealed improvement in the ITN-FRF cohort, which was superior to the delayed FRF cohort and the ITN monotherapy cohort. Specifically, the concurrently treated cohort (ITN-FRF) had a significant reduction in acne scar volume from baseline mean (151.1 ± 44.7 to 97.0 ± 31.2, p < 0.005), outperforming both the delayed FRF and monotherapy ITN treatment cohorts, respectively (155.4 ± 37.8 to 122.0 ± 46.2, 144.6 ± 82.8 to 132.4 ± 62.7). Additionally, the concurrently treated cohort demonstrated improved ECCA scores (36.8 ± 15.5), significantly better than the ITN monotherapy cohort (101.5 ± 20.1, p < 0.01). LIMITATIONS: Limited patient sample size: 38 patients completed the study; mostly Fitzpatrick Type II-III skin; photographic assessments utilized. CONCLUSION: Per our prospective trial, concurrent treatment of ITN-FRF is superior to delayed FRF treatment 6 months post-ITN cessation.

"You Have to Find a Way for This Child to Be at the Center": Pediatric Cardiologists' Views on Triadic Communication in Consultations on Congenital Heart Defects.

Congenital heart defects (CHDs) are present at birth and require ongoing management of personal, family, and medical aspects of care, including communication between family and medical staff. Effective communication is considered one of the main objectives of patient-centered care. Communication in pediatric medicine is especially challenging because it includes children and their parent(s), and children's cognitive and communication skills are still developing. Based on the model of behavior in pediatric communication , this study focused on pediatric cardiologists' views of the roles of children, parents, and physicians in the triadic encounter and their experiences in communicating information on pediatric CHDs in medical encounters. Semi-structured interviews were conducted with 17 experienced pediatric cardiologists and cardiac surgeons (five women and 12 men) at three medical centers in Israel. The grounded theory approach was used to identify three main categories: (1) the positioning (centrality) of the child in the setting (ideal vs. actual situation), (2) addressing parents' emotional needs, and (3) the physician's role as mediator between parent(s) and child. In each category, three elements are discussed: The physician's agenda, obstacles and challenges, and the physician's practical methods. Physicians strongly support children's involvement in triadic encounters yet face challenges in effectively integrating them into the information exchange process during cardiology consultations. Struggling to balance the principles of patient- and family-centered care, and without clear guidelines, they rely on their personal beliefs and experiences to formulate communication strategies that address parents' and children's needs.

The contribution of medical burden to 22q11.2 deletion syndrome quality of life and functioning.

PURPOSE: To date, there is no systematic method to quantify the medical burden of individuals with 22q11.2 deletion syndrome (22q11.2DS). This study aimed to design a Medical Burden Scale for 22q11.2DS to evaluate the effect of medical symptoms severity on quality of life (QoL) and functioning in individuals with this syndrome. METHODS: Individuals with 22q11.2DS (n = 76) were included in the study. A multidisciplinary group of physicians determined the severity of symptoms (on a scale of 0 to 4) of 8 major medical systems affected in 22q11.2DS, as well as the level of cognitive deficits and psychiatric morbidity. Regression models were used to evaluate the impact of medical, cognitive, and psychiatric symptoms' severity on global assessment of functioning (GAF) and QoL. RESULTS: The total Medical Burden Scale score was significantly associated with both QoL and GAF scores, beyond the effect of the psychiatric and cognitive deficits. We also found that QoL and GAF scores were associated with the severity scores of specific medical systems, particularly neurological symptoms, but also cardiovascular, ear-nose-throat, endocrinology, and orthopedics. CONCLUSION: Quantifying the medical burden of 22q11.2DS individuals is feasible and indicates the overall and specific contribution of medical symptoms to QoL and functioning of 22q11.2DS individuals.

Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.

BACKGROUND: The molecular basis of heterotaxy and congenital heart malformations associated with disruption of left-right asymmetry is broad and heterogenous, with over 25 genes implicated in its pathogenesis thus far. OBJECTIVE: We sought to elucidate the molecular basis of laterality disorders and associated congenital heart defects in a cohort of 30 unrelated probands of Arab-Muslim descent, using next-generation sequencing techniques. METHODS: Detailed clinical phenotyping followed by whole-exome sequencing (WES) was pursued for each of the probands and their parents (when available). Sanger sequencing was used for segregation analysis of disease-causing mutations in the families. RESULTS: Using WES, we reached a molecular diagnosis for 17 of the 30 probands (56.7%). Genes known to be associated with heterotaxy and/or primary ciliary dyskinesia, in which homozygous pathogenic or likely pathogenic variants were detected, included CFAP53 (CCDC11), CFAP298 (C21orf59), CFAP300, LRRC6, GDF1, DNAAF1, DNAH5, CCDC39, CCDC40, PKD1L1 and TTC25. Additionally, we detected a homozygous disease causing mutation in DAND5, as a novel recessive monogenic cause for heterotaxy in humans. Three additional probands were found to harbour variants of uncertain significance. These included variants in DNAH6, HYDIN, CELSR1 and CFAP46. CONCLUSIONS: Our findings contribute to the current knowledge regarding monogenic causes of heterotaxy and its associated congenital heart defects and underscore the role of next-generation sequencing techniques in the diagnostic workup of such patients, and especially among consanguineous families.

[MATERNAL SERUM ANGIOGENIC FACTORS AS AN AIDING TOOL FOR SCREENING WOMEN WITH SUSPECTED PREECLAMPSIA NEAR DELIVERY - INITIAL DATA AND AN ESTIMATED COST-BENEFIT].

INTRODUCTION: Preeclampsia (PE) is a major pregnancy complication, posing considerable morbidity and mortality. The maternal serum angiogenic factors - PlGF and sFlt-1, and their ratio appear to be promising markers to predict PE. Aims: To assess whether the evaluation of PlGF and sFlt-1 adds to the clinical workup of women with suspected PE, and to estimate the cost/benefit. METHODS: We prospectively enrolled pregnant women with suspected PE who were admitted to the Maternal-Fetal Medicine Unit (MFM) at Shamir Medical Center. Pregnancy and delivery records were collected from their computerized electronic medical records. PlGF<150pg/ml and sFlt-1/PlGF>38 measured prospectively were used to predict PE. RESULTS: Of 105 women included, 28 were in the control group with unrelated complications and none developed PE. Among 66 women with suspected PE, 27(41%) developed the syndrome, with a positive predictive value (PPV) of 90.3% for PlGF<150 pg/ml and 88.9% for sFlt-1/PlGFabove 38. Out of 11 women with suspected intrauterine growth restriction (IUGR), six developed the syndrome, and among them, the negative predictive value (NPV) was ~ 90%. CONCLUSIONS: Angiogenic factors are reliable in predicting PE near delivery. Of 8355 annual deliveries, 584 were admitted for suspected PE. The annual test cost was NIS 66,576 (NIS 140 per single test). Cost-saving was NIS 2.18 million, the ratio of cost saved vs. test cost was 32.7. DISCUSSION: The angiogenic factors are efficient and cost-saving in PE prediction near delivery. A larger study is necessary to determine the inclusion of angiogenic factors in the workup for suspected PE.

Clinical Features in a Large Cohort of Patients With 22q11.2 Deletion Syndrome.

OBJECTIVES: To evaluate various clinical aspects, specifically regarding immune status, in a large cohort of patients with DiGeorge syndrome. STUDY DESIGN: Data were collected for 98 patients with DiGeorge syndrome treated at a tertiary medical center. This included general information, laboratory results, and clinical features. RESULTS: The median age at diagnosis was 2.0 years (range, 0.0-36.5 years). The most common symptoms that led to diagnosis were congenital heart defect, speech delay, palate anomalies, and developmental delay. Common clinical features included recurrent infections (76 patients), congenital heart diseases (61 patients), and otorhinolaryngology disorders (61 patients). Twenty patients had anemia; the incidence was relatively high among patients aged 6-59 months. Thrombocytopenia was present in 20 patients. Recurrent chest infections were significantly higher in patients with T cell and T cell subset deficiencies. Decreased T cell receptor excision circles were more common with increasing age (P < .001). Of the 27 patients hospitalized due to infection, pneumonia was a leading cause in 13. CONCLUSIONS: Awareness of DiGeorge syndrome's typical and uncommon characteristics is important to improve diagnosis, treatment, surveillance, and follow-up.

Immune and TRG repertoire signature of the thymus in Down syndrome patients.

BACKGROUND: Patients with Down syndrome (DS) are at increased risk for infections and autoimmune disorders. Although several immunological abnormalities were previously found, differences in T cell receptor repertoire have never been shown. Thus we compared the T cell receptor gamma (TRG) repertoire in DS and non-syndromic pediatric patients by next-generation sequencing, in addition to other immunological markers. METHODS: Genomic DNA was extracted from thymuses of pediatric patients who underwent heart surgery, where six were with DS and six were non-syndromic patients. Peripheral blood counts, T cell subpopulations, thymus TCR excision circles (TRECs), spectratyping, and next-generation sequencing for TRG were analyzed. RESULTS: The mean age of the patients was 7 months and the mean lymphocyte count was slightly lower in patients with DS, whereas thymus TREC results were similar to non-syndromic patients (p = 0.197). The TRG repertoire analysis showed that patients with DS had a significantly larger number of unique TRG sequences, together with decreased clonal expansion. Lastly, the V and J gene usages in the thymus were similar in DS and non-syndromic patients. CONCLUSIONS: Patients with DS showed increased TRG repertoire diversity with decreased clonal expansion compared to non-syndromic patients. IMPACT: Alterations in T cell receptor gamma repertoire were found in patients with Down syndrome using next-generation sequencing (NGS) technique. Patients showed increased repertoire diversity and decreased clonal expansion compared to controls. These findings add to previous reports on abnormalities of other immune system components in patients with Down syndrome. NGS technique may point out differences not seen by previous methods. Repertoire abnormalities may contribute to those patients' predisposition to infections and autoimmune diseases.

Inappropriate Shocks and Power Delivery Using Adult Automatic External Defibrillator Pads in a Pediatric Patient.

ABSTRACT: The use of automatic external defibrillators (AEDs) during pulseless resuscitations is considered safe and reliable, and was established as part of the guidelines in out-of-hospital events. Based on extensive studies, the use of the standard AED is now indicated in every age group with a preference of pediatric pad application for small children and babies. If unavailable, adult pads are recommended. We report a case of 2 inappropriate AED shocks that were delivered to a neonate during a pulseless resuscitation after application of adult pads. The 3.6-kg patient received 2 shocks, over 200 J each, for sinus bradycardia that was not detected by the device. Although treated inappropriately with high voltage, no cardiac or skin sequelae were detected, and the patient had normal cardiac and neurological development later on.

A founder truncating variant in GDF1 causes autosomal-recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds.

The genetic basis of congenital heart malformations associated with disruption of left-right (L-R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left-right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab-Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left-right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.

Endocrine manifestations in children with Williams-Beuren syndrome.

AIM: Endocrine abnormalities in Williams-Beuren syndrome (WBS) include growth retardation, precocious puberty, hypercalcaemia and thyroid disorders. We aimed to characterise these abnormalities in a national cohort of children with WBS. METHODS: A retrospective study comprising a national cohort of individuals with WBS in Israel (16 males, 18 females) followed between 2010 and 2016. RESULTS: The age at diagnosis of WBS was 1.4 ± 1.0 years. Height standard deviation score (SDS) at last visit was correlated with the midparental height SDS (r = 0.46 p = 0.007). Yet, participants did not reach their midparental height, with a difference of 1.40 ± 0.85SD (p < 0.001). Short stature below the 3rd percentile was found in 14 participants (41%). Mean insulin-like growth factor 1 SDS was low (-0.61 ± 1.64) and was correlated with the mean height SDS (r = 0.63 p = 0.038). Two participants were diagnosed with growth hormone deficiency, and initiation of growth hormone treatment improved their height velocity. A total of eight participants (23.5%) had mild hypercalcaemia, five girls (14.7%) had precocious puberty and five participants (14.7%) had thyroid abnormalities. CONCLUSION: Individuals with WBS had a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Precocious puberty, hypercalcaemia and thyroid abnormalities should be screened for and treated as needed.

[PRINCIPLES FOR THE INTERPRETATION OF CARDIOPULMONARY EXERCISE TESTS (CPET)].

INTRODUCTION: The cardiopulmonary exercise test (CPET) permits the most accurate and reproducible quantification of cardiopulmonary fitness, a grading of the etiology and severity of cardiopulmonary impairments, and an objective assessment of the response to an intervention. Moreover, over the last three decades, a large volume of research has been directed toward the utility of CPET as a diagnostic and prognostic tool; these studies have established CPET as a scientifically sound and, therefore, clinically valuable method for accurately assessing exercise limitation and prognosis in various disease states. The CPET is relatively easy to perform, yet complex in the interpretation of the results. The current review presents the principles of the analytic process of the test results, in order to obtain possible diagnoses.

Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features including endocrine abnormalities. We aimed to characterize growth patterns, hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS. Anthropometric and laboratory measurements were obtained from the charts of 48 individuals (males=28, 8.0±6.8 visits/participant) followed at a national 22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3±4.9 years and age at last evaluation 11.2±7.2 years. Median height-SDS was negative at all ages. Height-SDS at last visit was correlated to the midparental height-SDS (r=0.52 P=0.002). Yet, participants did not reach their target height, with a difference of 1.06±1.07 SD (P <0.0001). Height-SDS at last visit of participants with a heart defect was lower compared to participants with a normal heart (-1.5±1.4 vs. -0.6±0.8, P=0.036), with lower height-SDS in the subgroup of participants with severe heart defects (-2.1±1.6, P=0.009). Mean IGF1-SDS was low (-0.99±1.68) but was not correlated with height-SDS. Thirteen patients (27%) had hypoparathyroidism: 10 presented during infancy and 3 during adolescence. Five patients (10.4%, female=4) had thyroid abnormalities. In conclusions, individuals with 22q11.2 DS have a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Hypoparathyroidism is common and may present during the neonatal period as well as later in life. Thyroid abnormalities may present during childhood, adolescence, or adulthood.

Changes in fitness are associated with changes in body composition and bone health in children after cancer.

AIM: This study examined the effects of physical activity on the fitness, body composition and mental health of children after cancer or bone marrow transplantation. METHODS: We focused on 22 children aged from seven to 14 years who had received chemotherapy and/or bone marrow transplantation in our medical centre. Ten children took part in a six-month exercise programme, and 12 children who did not exercise formed the control group. At baseline and at the end of the trial, we measured aerobic fitness, body composition, bone density and assessed the child's mood and quality of life. We pooled all participants together post hoc to compare changes in fitness with the various study outcomes. RESULTS: We found no differences between groups in changes in fitness, body composition or mental health indices. Significant correlations were found between changes in aerobic fitness and changes in lean body mass (r = 0.74, p = 0.002), bone mineral content (r = 0.57, p = 0.026) and femoral neck bone mineral density (r = 0.59, p = 0.027) in all participants. CONCLUSION: Group-based exercise training did not improve aerobic fitness in children after cancer or bone marrow transplantation. However, changes in fitness throughout the study period were associated with changes in body composition and bone health in all participants.

Exercise Performance in Children and Young Adults After Complete and Incomplete Repair of Congenital Heart Disease.

Few previous studies have addressed exercise capacity in patients with corrected congenital heart disease (CHD) and significant anatomical residua. The aim of this study was to determine the aerobic fitness and peak cardiac function of patients with corrected CHD with complete or incomplete repairs, as determined by resting echocardiography. Children, adolescents and young adults (<40 years) with CHD from both sexes, who had previously undergone biventricular corrective therapeutic interventions (n = 73), and non-CHD control participants (n = 76) underwent cardiopulmonary exercise testing. The CHD group was further divided according to the absence/presence of significant anatomical residua on a resting echocardiogram ("complete"/"incomplete" repair groups). Aerobic fitness and cardiac function were compared between groups using linear regression and analysis of covariance. Peak oxygen consumption, O2 pulse and ventilatory threshold were significantly lower in CHD patients compared with controls (all p < 0.01). Compared with the complete repair group, the incomplete repair group had a significantly lower mean peak work rate, age-adjusted O2 pulse (expressed as % predicted) and a higher VE/VCO2 ratio (all p ≤ 0.05). Peak oxygen consumption was comparable between the subgroups. Patients after corrected CHD have lower peak and submaximal exercise parameters. Patients with incomplete repair of their heart defect had decreased aerobic fitness, with evidence of impaired peak cardiac function and lower pulmonary perfusion. Patients that had undergone a complete repair had decreased aerobic fitness attributed only to deconditioning. These newly identified differences explain why in previous studies, the lowest fitness was seen in patients with the most hemodynamically significant heart malformations.

The Fate of Mitral Valve Surgery in the Pediatric Age: A 25-Year Single-Center Experience.

Background: The aim of this study was to evaluate the natural history of patients after mitral valve intervention in the pediatric age. Methods: This is a retrospective study including all patients who underwent mitral valve surgery from 1998 to 2022. The patients' surgical reports, postoperative records, and ambulatory visits were reviewed. The endpoints of the study were survival and freedom from mitral valve reoperation. Results: Of the 70 patients included in the cohort, 61 patients (86.7%) had congenital mitral valve disease, of whom 46 patients (75.4%) had a predominantly mitral regurgitation lesion, and 15 patients (24.6%) had a predominantly mitral stenosis. In the mitral regurgitation group, all of the patients underwent valve repair with an operative mortality of one patient (2.1%), and with median follow-up of 4 years (range, 0.5-13 years), there was 4.3% mortality (n = 2) and 71.2% freedom from reoperation. In the mitral stenosis group, 11 patients underwent mitral valve repair, and 4 patients underwent valve replacement. There was an operative mortality of two patients (13.3%). With a 2-year median follow-up (range: 0.1-23 years), there were no additional mortality cases in the mitral stenosis group. All three patients who survived primary mitral valve replacement (100%) and four patients who survived a primary repair (40.0%) underwent reoperation. Conclusions: This study demonstrates encouraging outcomes for mitral valve repair. The mortality of patients with congenital mitral valve disease may also be related to a difficult postoperative course, rather than the MV lesion itself.

[Aerobic fitness and cardiorespiratory function of pediatric cancer survivors].

INTRODUCTION: Overall, more than 80% of children diagnosed with cancer will survive their immediate disease. This growing group of childhood cancer survivors is at an increased risk for several chronic diseases and increased mortality. Physical activity is a well-known and powerful means to reduce such complications, yet many children are not active as recommended. Furthermore, the complex treatments might adversely affect the heart and lungs, possibly limiting physical performance. AIM: To measure aerobic fitness among childhood cancer survivors, while assessing maximal cardiac and respiratory functions. METHODS: Eighteen children (mean age 11.5 +/- 2.1 years, 50% males) who had completed medical treatment for cancer, and 16 healthy children, performed a cardiorespiratory exercise test on a bicycle ergometer until exhaustion. Peak oxygen uptake, O2 pulse and several ventilatory parameters were measured and compared between the groups. RESULTS: The mean maximal load obtained by the cancer survivor group was lower than expected, compared with controls (89% +/- 19 vs. 101/% +/- 18, p = 0.055). Peak oxygen consumption was also lower, with a marginal statistical significance (33.3 +/- 7.5 vs. 38.9 +/- 9.7 ml O2/kg/min, p = 0.075), yet was significantly lower when expressed as a percent of age- and sex- appropriate norms [78% +/- 15 vs. 94% +/- 16, p = 0.0081. Cardiac and respiratory functions were normal in all children, with no between-group differences. CONCLUSIONS: We conclude that aerobic fitness is lower in children who have survived cancer, with no evidence of significant cardiac or lung damage. Given the importance of regular physical activity for this at-risk population, it should be continuously encouraged, while administering a personally tailored exercise prescription.

Applicability of Transnasal Echography for Identification of Internal Carotid Artery.

OBJECTIVE: To study the applicability of transnasal echography for the internal carotid artery (ICA) imaging during endoscopic procedures, primarily nasopharyngectomy. STUDY DESIGN: Non-randomized controlled cohort. METHODS: The tip of a pediatric transducer for transesophageal echography was inserted into each nostril under endoscopic control and placed in the ipsilateral Rosenmuller's fossa. The ICA's internal diameter and distance between the nasopharyngeal wall and the artery's closest point were measured on each side. Two independent examiners measured the same parameters on the axial plane of the skull base computer tomography (CT). Agreement between CT and echography measurements was estimated by the Bland-Altman approach. RESULTS: Twenty-seven ICAs (sides) were available for the echography-CT agreement analysis. Inter method agreement for both parameters was similar to the inter examiner agreement for the CT measurements. CONCLUSIONS: Our first study on endoscopic echography demonstrated that this method is applicable, potentially allowing safer transnasal surgery in the ICA vicinity. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1184-1188, 2022.

Differences in severity of cardiovascular anomalies in children with Noonan syndrome based on the causative gene.

Background: Noonan syndrome (NS) is a genetic syndrome, characterized by various dysmorphic features, cardiac anomalies, short stature, and developmental delay. NS is a leading cause of cardiovascular anomalies. The syndrome results from dysregulation in the RAS-MAPK pathway and is related to the RASopathy family syndromes. Pathogenic variants in more than 20 related genes have been identified in association with NS, and several genotype-phenotype correlations were suggested. The specific severity of the same cardiovascular anomalies has not been described as linked to a specific causative gene. Methods: For this retrospective, single-center study, data retrieved from medical charts of a multidisciplinary NS clinic included genetic diagnosis, cardiac malformations, the need for intervention, demographics, and prenatal diagnosis. We analyzed molecular genetics and the severity of cardiac malformations. Results: The cohort comprised 74 children with NS. Consistent with previous studies, pathogenic variants in PTPN11 were the most common (62%). Cardiovascular anomalies presented in 57%; pulmonary stenosis (PS) was the most common (about 79% of anomalies). In children with pathogenic variants in PTPN11, PS tended to be more severe and required intervention in 53%, compared to 25% of children with PS and a variant in other genes. Conclusion: This first Israeli cohort of NS showed similar rates of cardiac malformations and genetic breakdown as previously published. Variants in PTPN11 were prone to a higher risk for severe PS that requires intervention. This finding may assist in genetic counseling and cardiac treatment decisions, and stresses the importance of genetic in addition to clinical diagnosis of NS.

Comparison of Speckle Tracking Echocardiography During Different Pacing Modalities for Cardiac Resynchronization Therapy Response Prediction.

Background: The aim of this study was to evaluate left ventricular mechanical activation pattern by speckle tracking echocardiography (STE) as a predictor of response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods: Echocardiography was performed during no pacing, right ventricular pacing (RVP), biventricular pacing (BVP) and multipolar pacing (MPP) immediately after CRT implantation in 16 patients at a single centre. Seven patients were diagnosed as responders and 9 patients as non-responders after 6 months of standard CRT pacing. All had adequate short axis views, and 1 CRT responder and 2 CRT non-responders had limited longitudinal views. Results: Longitudinal and circumferential global strain (GS) and global strain rate (GSR) or their change analysis, did not yield any CRT response prediction. However, the longitudinal BVP/RVP GS ratio was significantly higher in the responder group (1.32 ± 0.2%, 2.0 ± 0.4% and 1.9 ± 0.4%), compared with the non-responder group (1.06 ± 0.2%, 1.1 ± 0.4% and 1.2 ± 0.4%) in the apical two-chamber, APLAX and four-chamber views, respectively. Similarly, the longitudinal BVP/RVP GSR at active systolic phase (GSRs) was significantly higher in the responder group (1.9 ± 0.9% and 1.7 ± 0.4%) compared with the non-responder group (1.0 ± 0.4% and 1.1 ± 0.2%) in the apical APLAX and four-chamber views, respectively. Measurements of the strain delay index showed predictive power regarding CRT response in non-paced patients. Conclusion: Post implantation, longitudinal BVP/RVP GS and GSRs ratios of 1.4% and above may be useful as a CRT response prediction tool. Furthermore, our findings support the usefulness of strain delay index prior to CRT implantation in non-paced patients.