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עמוד בית
Sat, 14.12.24

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January 2024
Karam Azem MD, Shai Fein MD MHA, Yuri Matatov MD, Philip Heesen MD, Leonid A Eidelman MD, Michael Yohay Stav MD, Yoel Shufaro MD PhD, Sharon Orbach-Zinger MD, Cristian Arzola MD MSc

Background: Pulmonary aspiration is a potentially lethal perioperative complication that can be precipitated by gastric insufflation. Face mask ventilation (FMV), a ubiquitous anesthetic procedure, can cause gastric insufflation. FMV with an inspiratory pressure of 15 cm H2O provides the best balance between adequate pulmonary ventilation and a low probability of gastric insufflation. There is no data about the effects of FMV > 120 seconds.

Objectives: To investigate the effect of prolonged FMV on gastric insufflation.

Methods: We conducted a prospective observational study at a tertiary medical center with female patients who underwent oocyte retrieval surgery under general anesthesia FMV. Pre- and postoperative gastric ultrasound examinations measured the gastric antral cross-sectional area to detect gastric insufflation. Pressure-controlled FMV with an inspiratory pressure of 15 cm H2O was continued from the anesthesia induction until the end of the surgery.

Results: The study comprised 49 patients. Baseline preoperative gastric ultrasound demonstrated optimal and good image quality. All supine measurements were feasible. The median duration of FMV was 13 minutes (interquartile range 9–18). In the postoperative period, gastric insufflation was detected in only 2 of 49 patients (4.1%). There was no association between the duration of FMV and delta gastric antral cross-sectional area (β -0.01; 95% confidence interval -0.04 to 0.01, P = 0.31).

Conclusions: Pressure-controlled FMV with an inspiratory pressure of 15 cm H2O carries a low incidence of gastric insufflations, not only as a bridge to a definitive airway but as an alternative ventilation method for relatively short procedures in selective populations.

November 2023
Lior Benjamin Pilas MD, Orit Gur BSc, Gidon Berger MD

Background: In the past decade, numerous new imaging and laboratory tests have been implemented that significantly contribute to improved medical diagnostic capabilities. However, inappropriate utilization, which occurs on a large scale, has significant ramifications for both patient care and health systems.

Objectives: To assess the impact of a novel clinical decision support system (CDSS) applied to our electronic medical records on abdominal ultrasonography utilization pattern.

Methods: We conducted a retrospective cohort study comparing patterns of abdominal ultrasound utilization in cases of liver enzyme elevation, with and without CDSS, between February and May in 2017 (before CDSS implementation) and during the same months in 2018 (after CDSS implementation). The following parameters were collected: number of tests ordered according to the guidelines, tests with a diagnostic value, and order forms completed with any data or a diagnostic question. The comparison was conducted using chi-square test.

Results: Of 152 abdominal ultrasound tests, 72 were ordered in the pre-implementation period and 80 in the post-implementation period. The system failed to reach statistical significance regarding the rates of ordered tests according to the guidelines and/or tests with a diagnostic value. However, the use of the CDSS had a statistically significant impact regarding completing the order form with data, including a specific diagnostic question.

Conclusions: The effect of the system on the efficiency of test utilization was partial. However, our findings strongly suggested that CDSS has the potential to promote proper usage of complementary technologies.

February 2023
Lior Baraf MD, Yuval Avidor MD, Anat Bahat Dinur MD, Uri Yoel MD, Benzion Samueli MD, Ben-Zion Joshua MD, Merav Fraenkel MD

Background: Due to the high variability in malignancy rate among cytologically indeterminate thyroid nodules (Bethesda categories III–V), the American Thyroid Association recommends that each center define its own categorical cancer risk.

Objectives: To assess cancer risk in patients with cytologically indeterminate thyroid nodules who were operated at our center.

Methods: In a retrospective study, we analyzed the pathology results of all the patients whose fine needle aspiration results showed Bethesda III–V cytology and who subsequently underwent total thyroidectomy or lobectomy from December 2013 to September 2017.

Results: We analyzed 56 patients with indeterminate cytology on fine needle aspiration. Twenty-nine (52%) were defined as Bethesda III, 19 (34%) Bethesda IV, and 8 (14%) Bethesda V category. Malignancy rates were 38%, 58%, and 100% for Bethesda categories III, IV, and V, respectively. Most malignancies in Bethesda categories III and IV were follicular in origin (follicular thyroid carcinoma and follicular type papillary thyroid carcinoma), while 100% of the patients with Bethesda category V were diagnosed with classical papillary thyroid carcinoma. No correlation was found between sonographic and cytological criteria of nodules with Bethesda categories III and IV and rates of malignancy.

Conclusions: We found higher than expected rates of malignancy in indeterminate cytology. This finding reinforces the guidelines of the American Thyroid Association to establish local malignancy rates for thyroid nodules with indetermined cytology.

January 2023
Alina Weissmann-Brenner MD, Vered Yulzari MD, Eran Kassif MD, Michal Zajicek MD

Background: Advances in examination techniques have improved routine assessment of non-gynecological structures in the pelvis.

Objectives: To describe the sonographic features of incidental urological abnormalities found during gynecological transvaginal ultrasound.

Methods: A retrospective descriptive analysis of patients who underwent gynecological ultrasound and were diagnosed with urologic findings was performed. The sonographic features of the findings including size, echogenicity, and vascularity were examined.

Results: Gynecological ultrasound diagnosed urological findings in nine women. Two had primary neoplasms of the urinary bladder, one had metastases to the urinary bladder, one had polyps in the distal ureters, four presented with calculus in the distal ureters (one of them was 19 weeks pregnant), and one showed diverticulum of the urethra. At presentation five women (56%) had urinary complaints. Two patients (22%) with abdominal pain with distal ureteral calculi had normal transabdominal ultrasound targeted to the urinary system prior to the gynecological sonography.

Conclusions: Transvaginal ultrasound is useful in the diagnosis of urological abnormalities, mainly in the urinary bladder and the distal ureters. We suggest adding transvaginal assessment for female patients with urinary complains in whom transabdominal ultrasound of urinary system was unremarkable.

Matityahou Ormianer MD, Benjamin Z. Koplewitz MD, Ron Eliashar MD, Menachem Gross MD, Jeffrey M. Weinberger MD, Nir Hirshoren MD

Background: Unilateral intratonsillar abscess (ITA) is an underreported, well-known complication of acute tonsillitis. The prevalence of unilateral ITA compared to peritonsillar abscess (PTA) is 1:14. However, bilateral ITA is an extremely rare entity, with only four cases reported thus far.

Objectives: To describe past cases and our experience, elaborating the diagnostic challenge and the surgical treatment for bilateral ITA.

Methods: We conducted a literature search in the PubMed database using the key words intra-tonsillar abscess, tonsillar abscess, bilateral tonsillar abscess, bilateral intra-tonsillar abscess and bilateral peritonsillar abscess. Our search was limited to the years 1980 to 2020.

Results: We found that only four cases of bilateral ITA were previously published. All were characterized by a delay in diagnosis with a median of 10 days (4–14 days), symmetrical oral cavity appearance, enlarged bilateral kissing tonsils, and subsequent treatment by surgical drainage/paracentesis. Respiratory compromise was a concern in most cases. Our patient was treated with bilateral quinsy tonsillectomy and had a prompt recovery.

Conclusions: Bilateral ITA is a rare, deceiving entity, with a diagnosis delay attributed to the symmetrical oral bulging. We present the fifth case reported and the first ever reported in a pediatric patient. We describe the assumed pathogenesis and the main characteristics among all five patients, emphasizing the important role of a high index of suspicion and appropriate imaging, guiding to proper diagnosis and treatment.

November 2022
Katya Meridor MD, Pnina Rotman-Pikielny MD, Or Carmi MD, Myriam Werner MD, Yair Levy MD

Background: Patients with systemic sclerosis (SSc) are at increased risk for autoimmune thyroid diseases, but information regarding thyroid nodules and cancer in SSc is scarce.

Objectives: To evaluate the thyroid gland in patients with SSc at a single Israeli center.

Methods: Thyroid workup was conducted in consecutive SSc patients: thyroid-stimulating hormone (TSH), free thyroxine (fT4), anti-thyroid peroxidase, and anti-thyroglobulin antibodies, as well as thyroid ultrasound and fine needle aspiration (FNA) when appropriate.

Results: Fifty patients, mean age 51.3 ± 13.5 years (44 women) were evaluated. Ten were previously diagnosed with thyroid disease. Median TSH level was 2.0 (normal range 0.23–4 mIU/l) and median fT4 level was 1.0 (normal range 0.8–2.0 ng/dL). Among the 40 thyroid disorder-naive patients, 3 had subclinical hypothyroidism and 5 had positive anti-thyroid antibodies; 22 (44%) had 1–6 thyroid nodules, which were ≥ 1 cm in 12 (24%). Accordingly, six patients underwent FNA, and five were diagnosed as colloid nodules and one as papillary carcinoma.

Conclusions: New cases of clinically significant autoimmune thyroid disease were not detected in our cohort of patients with SSc. Nevertheless, almost half had thyroid nodules. The clinical significance of these findings and their relation to thyroid cancer remains to be determined.

September 2022
The Rubrum Coelis Group*, and Jacob Chen MD MHA MSc, Alex Dobron BMedSc MOccH, Akiva Esterson BEMS MD, Lior Fuchs MD, Elon Glassberg MD MHA MBA, David Hoppenstein MBBCh, Regina Kalandarev-Wilson BEMS MD, Itamar Netzer MD MBA, Mor Nissan BEMS, Rachelly Shifer Ovsiovich DMD, Raphael Strugo MD, Oren Wacht BEMS MHA PhD, Chad G. Ball MD MSc FRCSC FACS, Naisan Garraway CD MD FRCSC FACS, Lawrence Gillman MD MMedEd FRCSC FACS, Andrew W. Kirkpatrick MD CD MHSc FRCSC FACS, Volker Kock CD MB, Paul McBeth MD MASc FRCS(C), Jessica McKee BA MSc, Juan Wachs PhD, and Scott K. d’Amours MDCM FRCSC FRACS FACS

Background: Handheld ultrasound devices present an opportunity for prehospital sonographic assessment of trauma, even in the hands of novice operators commonly found in military, maritime, or other austere environments. However, the reliability of such point-of-care ultrasound (POCUS) examinations by novices is rightly questioned. A common strategy being examined to mitigate this reliability gap is remote mentoring by an expert.

Objectives: To assess the feasibility of utilizing POCUS in the hands of novice military or civilian emergency medicine service (EMS) providers, with and without the use of telementoring. To assess the mitigating or exacerbating effect telementoring may have on operator stress.

Methods: Thirty-seven inexperienced physicians and EMTs serving as first responders in military or civilian EMS were randomized to receive or not receive telementoring during three POCUS trials: live model, Simbionix trainer, and jugular phantom. Salivary cortisol was obtained before and after the trial. Heart rate variability monitoring was performed throughout the trial.

Results: There were no significant differences in clinical performance between the two groups. Iatrogenic complications of jugular venous catheterization were reduced by 26% in the telementored group (P < 0.001). Salivary cortisol levels dropped by 39% (P < 0.001) in the telementored group. Heart rate variability data also suggested mitigation of stress.

Conclusions: Telementoring of POCUS tasks was not found to improve performance by novices, but findings suggest that it may mitigate caregiver stress.

April 2022
Victor G. Levin BSc, Ayal Romem MD MHA, Gali Epstein Shochet PhD, Ori Wand MD, David Dahan MD, and David Shitrit MD

Background: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently used method for obtaining tissue samples for the diagnosis of various respiratory conditions, including lung cancer staging. In most cases, EBUS-TBNA is performed under moderate sedation (MS). However, in cases of respiratory compromised patients, if this procedure is performed, it is conducted under general anesthesia (GA).

Objective: To assess the diagnostic yield of EBUS-TBNA among respiratory compromised patients.

Methods: Data of consecutive patients (n=191) who underwent EBUS-TBNA at our medical center between January 2019 and December 2019 were retrospectively analyzed. Respiratory compromised patients underwent GA and patients without respiratory compromise were mostly moderately sedated (MS). Characteristics, diagnostic yield, and complication rates were compared.

Results: Diagnostic yield was similar between the two sedation modes (89% in GA group and 78% in the MS group, P = 0.11). The number of total samples obtained per procedure was significantly higher in the GA vs. the MS group (4.1 ± 2.1 vs. 2.1 ± 1.33, P < 0.01). The overall complication rate was 13% and 20.9% in the GA vs. the MS groups, respectively (P = 0.14), with the most frequent complication being minor bleeding. Interestingly, while the number of brushings, bronchoalveolar lavage, and endobronchial biopsy were similar, the percent of subjects who underwent transbronchial biopsy was significantly higher in the GA group (49% vs. 24.2%, P < 0.01).

Conclusion: EBUS-TBNA performed under GA among respiratory compromised patients is safe and has similar diagnostic yield to that of patients without a respiratory compromise

November 2021
Miki Paker MD, Tal Goldman MD, Muhamed Masalha MD, Lev Shlizerman MD, Salim Mazzawi MD, Dror Ashkenazi MD, and Rami Ghanayim MD

Background: The 2015 American Thyroid Association (ATA2015) and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS) are two widely used thyroid sonographic systems.

Objectives: To compare the two systems for accuracy of cancer risk prediction.

Methods: Preoperative ultrasound images from 265 patients who underwent thyroidectomy at our hospital from January 2012 to March 2019 were retrospectively categorized by the ACR TI-RADS and ATA2015 systems. Diagnostic performances were compared.

Results: Of 238 nodules assessed, 115 were malignant. Malignancy risks for the five ACR TI-RADS categories were 0%, 7.5%, 11.4%, 59.6%, and 90.0%. Malignancy risks for the five ATA2015 categories were 0%, 6.8%, 17.0%, 55.5%, and 92.1%. The proportion of total nodules biopsied was higher with the ATA2015 system than the ACR TI-RADS system: 88.7% vs. 66.3%. Proportions of malignant nodules and benign nodules biopsied were higher with ATA2015 than with ACR TI-RADS: 93.3% vs. 87.8% and 84.4% vs. 46.3%, respectively. Specificity and sensitivity rates were 53.6% and 84.3%, respectively, for ACR TI-RADS, and 15.5% and 93.3%, respectively, for ATA2015. The two systems showed similarly accurate diagnostic performance (AUC > 0.88). False negative rates for ACR TI-RADS and ATA2015 were 15.6% and 6.6%, respectively. Rates of missed aggressive cancer were similar for the two systems: 3.4% and 3.7%, respectively.

Conclusion: ACR TI-RADS was superior to ATA2015 in specificity and avoiding unnecessary biopsies. ATA2015 yielded better sensitivity and a lower false negative rate. Identification of aggressive cancers was identical in the two systems

September 2021
Roy Rafael Dayan MD, Yosef Ayzenberg MD, Tzachi Slutsky MD, Ela Shaer MD, Alon Kaplan BMedSc, and Vladimir Zeldetz MD

Background: Limited data exist regarding the safety of ultrasound-guided femoral nerve blockade (US-FNB) in patients with hip fractures treated with anti-Xa direct oral anticoagulants (DOAC).

Objectives: To compare the safety outcomes of US-FNB to conventional analgesia in patients with hip fractures treated with anti-Xa DOAC.

Methods: This observational exploratory prospective study included 69 patients who presented to our emergency department (ED) in 3 years with hip fracture and who were treated with apixaban or rivaroxaban. Patients received either a US-FNB (n=19) or conventional analgesics (n=50) based on their preference and, and the presence of a trained ED physician qualified in performing US-FNB. Patients were observed for major bleeding events during and 30 days after hospitalization. The degree of preoperative pain and opioid use were also observed.

Results: We found no significant difference in the number of major bleeding events between groups (47.4% vs. 54.0%, P = 0.84). Degree of pain measured 3 and 12 hours after presentation was found to be lower in the US-FNB group (median visual analog scale of pain improvement from baseline of -5 vs. -3 (P = 0.002) and -5 vs.-4 (P = 0.023), respectively. Opioid administration pre-surgery was found to be more than three times more common in the conventional analgesia group (26.3% vs.80%, P < 0.0001).

Conclusions: Regarding patients treated with Anti-Xa DOAC, US-FNB was not associated with an increase in major bleeding events compared to conventional analgesia, although it was an effective means of pain alleviation. Larger scale randomized controlled trials are required to determine long-term safety and efficacy.

July 2021
Ramona Lucchetti MD, Fulvia Ceccarelli MD PhD, Enrica Cipriano MD, Carlo Perricone MD PhD, Francesca Romana Spinelli MD PhD, Cristiano Alessandri MD, and Fabrizio Conti MD

Background: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by different phenotypes in terms of joint involvement. The so-called oligoarticular pattern involves fewer than five active joints at a different time points. The evaluation of disease activity in this subset of patients is an unmet need due to the lack of specific indices able to capture modifications over time.

Objectives: To evaluate the ability of musculoskeletal ultrasound to monitor the response to apremilast treatment in oligoarticular PsA patients.

Methods: We evaluated 24 oligoarticular patients (19 women, 5 men; median age 56 years, interquartile range (IQR) 19; median disease duration 5 years, IQR 5.75). All patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 (T3) weeks. Clinical assessment included evaluation of 66 swollen joints and patient global health assessment. All the patients underwent ultrasound assessment of the clinically involved joints. Synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0–3). The total inflammatory score was the sum of the scores.

Results: We found a reduction in the ultrasound inflammatory score at all time points, with a significant improvement at 6 and 12 weeks of treatment compared with baseline: T0 median 8.5 (IQR 5.0); T1 3.5 (3.0); T2 2.0 (3.5); P  = 0.01. We observed a significant reduction of patient global health assessment after 24 weeks (T0 median 50 (32.5); T3 40 (57.5); P = 0.01).

Conclusions: Musculoskeletal ultrasound could be useful in the assessment of treatment response in PsA patients with oligoarticular subset

January 2021
Natav Hendin BSc, Gabriel Levin MD, Abraham Tsur MD, Hadas Ilan MD, Amihai Rottenstreich MD, and Raanan Meyer MD

Background: The sonographic assessment of estimated fetal weight (EFW) is essential for identification of fetuses in weight extremes and aids in peripartum management. However, there are inconsistent reports regarding EFW accuracy.

Objective: To examine maternal and fetal determinants associated with unreliable EFW.

Methods: A retrospective case-control study was conducted at a single, tertiary medical center between 2011 and 2019. All term, singleton deliveries with a sonographic EFW within 2 weeks of delivery were included. Unreliable EFW was defined as > 500 grams discordance between it and the actual birth weight. We allocated the study cohort into two groups: unreliable EFW (cases) and accurate EFW (controls).

Results: Overall, 41,261 deliveries met inclusion criteria. Of these, 1721 (4.17%) had unreliable EFW. The factors positively associated with unreliable EFW included body mass index > 30 kg/m2, weight gain > 20 kg, higher amniotic fluid index, pregestational diabetes, gestational age > 410/7, and birth weight ≥ 4000 grams. On multiple regression analysis, pregestational diabetes (odds ratio [OR] 2.22, 95% confidence interval [95%CI] 1.56–3.17, P < 0.001) and a higher birth weight (OR 1.91, 95%CI 1.79–2.04, P < 0.001) were independently associated with unreliable EFW. On analysis of different weight categories, pregestational diabetes was associated with unreliable EFW only among birth weights ≥ 3500 grams (OR 3.28, 95%CI 1.98–5.44, P< 0.001) and ≥ 4000 grams (OR 4.27, 95%CI 2.31–7.90, P < 0.001).

Conclusion: Pregestational diabetes and increased birth weight are independent risk factors for unreliable EFW and should be considered when planning delivery management.

December 2020
Oren Elyah MD and Sumit Chatterji MD FRCP

Background: Our 1600-bed teaching hospital opened the first physician-led specialist pleural service in Israel in November 2016. Thoracentesis is one of the frequently performed procedures in clinic.

Objectives: To review the incidence of thoracentesis-related symptoms, complications, and risk factors in a specialist pleural clinic.

Methods: Prospective analysis was conducted of 658 ultrasound-assisted thoracenteses between November 2016 and November 2019. Data were collected on patient demographics, clinical characteristics, procedural aspects, symptoms, complications, and additional interventions required.

Results: Of the procedures, 24% were accompanied by a reported symptom of any intensity or duration. Cough and chest discomfort were noted in 56.4% and 52% of these cases, respectively. Large-volume drainage was associated with symptoms (P = 0.002). Ultrasound-estimated effusion volume before drainage predicted pain (P = 0.001) and pneumothorax (P = 0.021). Of 8 cases of pneumothorax, 6 were due to non-expandable lung. Two patients were hospitalized (0.3%), and one required a chest drain.

Conclusions: Symptoms are a common feature of thoracentesis even when performed by experienced operators in ideal settings. Complications, however, are rare when the procedure is performed with bedside ultrasound and attention is paid to patient-reported symptoms and volume drained. Specialist pleural clinics provide a good model for a standardized approach to safe performance of this common procedure.

July 2020
Fulvia Ceccarelli MD PhD, Enrica Cipriano MD, Francesco Natalucci MD, Carlo Perricone MD PhD, Giulio Olivieri MD, Valeria Orefice MD, Francesca Morello MD, Cristiano Alessandri MD, Francesca R. Spinelli MD PhD and Fabrizio Conti MD

Background: Belimumab was the first biological drug approved for the treatment of systemic lupus erythematosus (SLE) patients. Phase II/III randomized controlled trials and real-life studies identified patients with musculoskeletal involvement as best responders.

Objective: To evaluate the effectiveness of belimumab in SLE-related joint involvement.

Methods: The cohort comprised SLE patients receiving belimumab for musculoskeletal indications. Belimumab was intravenously administrated according to protocols; all the patients were evaluated at baseline (T0) and after 3 (T1), 6 (T2), and 12 (T3) months. We assessed joint activity by disease activity score 28, simple disease activity index (SDAI), clinical disease activity index (CDAI), and swollen tender ratio. Each patient underwent musculoskeletal ultrasound of 34 joints to assess synovial effusion synovial hypertrophy, and power Doppler; by using a semi-quantitative scale (0–3) we obtained the total inflammatory score (0–216).

Results: We evaluated 20 patients (males/females 1/19, median age 45 years [interquartile range (IQR) 12], median disease duration 144 months [IQR 144]). CDAI and SDAI significantly decreased at T1 (P = 0.02 and P = 0.01 respectively) and this improvement was maintained at the following time-points (CDAI: T2 P = 0.008, T3 P = 0.004; SDAI: T2 P = 0.006, T3 P = 0.01). A significant reduction of median ultrasound score was identified at T1 (T0 20.5 [IQR 13.5] vs. T1 7.5 [IQR 4.7], P < 0.001), and maintained at T2 (7.0 [IQR 5], P < 0.0001), and T3 (7.0 [IQR 9.0], P < 0.0001).

Conclusions: Belimumab induces a sustained improvement of ultrasound-detected inflammatory status at the articular level.

January 2020
Alina Weissmann-Brenner MD, Anna Mitlin MD, Chen Hoffman MD, Reuven Achiron MD, Yishai Salem MD and Eldad Katorza MD

Background: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD.

Objectives: To examine the correlation between CHD and brain injury using fetal brain MRI.

Methods: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations.

Results: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group.

Conclusions: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.

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