Cytological and Ultrasound Features of Thyroid Nodules Correlate With Histotypes and Variants of Thyroid Carcinoma.

CONTEXT: Prognosis is excellent for papillary thyroid carcinoma (PTC), noninvasive follicular thyroid neoplasia with papillary-like nuclear features (NIFT-P), and follicular thyroid carcinoma (FTC) but is poor for poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). Among PTCs, the prognosis is more favorable for follicular (FV-PTC) and classic (CV-PTC) than for tall cell (TCV-PTC), and solid (SV-PTC) variants. OBJECTIVE: To associate histotypes and variants of thyroid carcinoma with ultrasound and cytological features. METHODS: Histology of 1018 benign tumors and 514 PTC (249 CV, 167 FV, 49 TC, 34 SV, and 15 other variants), 52 NIFT-P, 50 FTC, 11 PDTC, and 3 ATC was correlated with fine-needle aspiration biopsy categories (Italian classification: TIR1, TIR2, TIR3A, TIR3B, TIR4, and TIR5) and ultrasound features at the Endocrinology Unit, University Hospital of Pisa. In total, 1117 patients with thyroid nodule(s) who underwent thyroidectomy were included. RESULTS: Of PTC, 36.3% had indeterminate cytology (TIR3A or TIR3B), 56.6% were suspicious for malignancy or malignant (TIR4 or TIR5); 84.0% FTC and 69.3% NIFT-P were TIR3A or TIR3B; 72.5% FV-PTC and 73.6% SV-PTC were TIR3A or TIR3B; 79.9% CV-PTC and 95.9% TCV-PTC were TIR4 or TIR5. The association of a hypoechoic pattern, irregular margins, and no microcalcifications was more frequent in TCV-PTC than in CV-PTC (P = .02, positive predictive value = 38.9%; negative predictive value = 85.5%). CONCLUSION: At cytology, most FTC, NIFT-P, FV-PTC, and SV-PTC were indeterminate, most CV-PTC and TCV-PTC were suspicious for malignancy or malignant. Ultrasound can be helpful in ruling out TCV-PTC.

Off-pump injectable versus on-pump conventional tissue valves for pulmonary valve replacement: the injectable valve implantation randomised trial (INVITE).

OBJECTIVES: To assess the effectiveness of injectable tissue pulmonary valve compared with standard pulmonary valve in patients requiring pulmonary valve replacement surgery. DESIGN: A multicentre, single-blind, parallel two-group randomised controlled trial. Participants were blind to their allocation. Follow-up continued for 6 months. Randomised allocations were generated by a computer using block randomisation, stratified by centre. SETTING: Two National Health Service secondary care centres in the UK. PARTICIPANTS: People aged 12-80 years requiring pulmonary valve replacement. INTERVENTIONS: Participants were randomly allocated (1:1 ratio) to injectable pulmonary valve replacement (IPVR) without cardiopulmonary bypass (CPB) or standard pulmonary valve replacement (SPVR) with CPB. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was chest drainage volume over the first 24 hours after surgery. Secondary outcomes included in-hospital clinical outcomes; valve and heart function 6 months postsurgery and health-related quality of life 6 weeks and 6 months postsurgery. RESULTS: Nineteen participants agreed to take part. Eleven were allocated to IPVR and eight to SPVR. The trial was stopped before the target sample size of 60 participants was reached due to challenges in recruitment. The primary analysis includes all randomised participants; there were no withdrawals. Chest drain volume 24 hours after surgery was on average 277.6 mL lower with IPVR (IPVR mean 340.0 mL; SPVR mean 633.8 mL; mean difference, -277.6; 95% CI, -484.0 to -71.2; p=0.005). There were no statistically significant differences in time to readiness for extubation (p=0.476), time to fitness for discharge (p=0.577) and time to first discharge from the intensive care unit (p=0.209). Six participants with IPVR required CPB. Safety profiles and quality of life scores were similar. CONCLUSIONS: IPVR reduced chest drain volume despite >50% of participants requiring CPB. There was no evidence of any other benefit of IPVR. TRIAL REGISTRATION NUMBER: ISRCTN23538073.

The tricuspid valve in hypoplastic left heart syndrome: Echocardiography provides insight into anatomy and function.

Tricuspid regurgitation (TR) is commonly seen in surgically palliated patients with hypoplastic left heart syndrome, and when significant, is associated with an increase in both morbidity and mortality. Tricuspid valve dysfunction appears to be the result of a combination of inherent structural malformations and the unique physiological circumstances resulting from right ventricular pressure and volume overload. Valve dysfunction evolves rapidly, and manifests early on in the surgical pathway. Whilst traditional echocardiographic imaging can identify anatomical defects and dysfunction resulting in varying degrees of regurgitation even at early stages, more sophisticated investigations such as 3D echocardiography, strain imaging and transesophageal 3DE might prove useful to better demonstrate the complex interactions between abnormal anatomy of the valve complex, ventricular function, mechanical synchrony, and TR. Recognition of specific mechanisms of TR can enhance patient-specific care by directing precise surgical interventions and by informing the best timing for intervention on the valve.

Thyroid autoimmunity, thyroglobulin autoantibodies, and thyroid cancer prognosis.

The relevance of thyroid autoimmunity to the prognosis of papillary thyroid carcinoma is still unsettled. We decided to investigate the impact of thyroid autoimmunity on the prognosis of papillary thyroid carcinoma and the handling of TgAbs. We evaluated the clinical course of a large group of patients according to the presence (PTC-LT) or absence (PTC) of lymphocytic thyroiditis at histology. We studied 194 consecutive patients with a diagnosis of PTC and treated them with total thyroidectomy plus ¹³¹I ablation between 2007 and 2009. Median follow-up (with 25th-75th percentiles) was 84.0 (56.4-118.0) months. The remission criteria were: basal Tg < 0.2 ng/mL (or stimulated Tg: < 1), TgAbs < 8 IU/mL (otherwise 'decreasing TgAb trend', a decline of ≥20% in sequential TgAb measurements) and unremarkable imaging. PTC-LT and PTC patients had comparable treatment.TgAbs were detectable in 72.5% of PTC-LT and 16.5% of PTC patients. Time to remission was longer in the detectable than in the undetectable TgAb cohort (28.5 vs· 7.5 months (median); HR: 0.54, CI: 0.35-0.83, P = 0.005). When comparing PTC-LT to PTC patients, the difference was maintained in the detectable TgAb (29.3 vs 13.0 months; HR: 0.38, CI: 0.18-0.80; P = 0.01) but not in the undetectable TgAb cohort (7.7 vs 7.3 months; HR: 0.90, CI: 0.55-1.47; P = 0.68). Using the decreasing TgAb trend, the influence of detectable TgAbs on time to remission was abolished. Thyroid autoimmunity does not influence the prognosis of papillary thyroid carcinoma. A decreasing TgAb trend seems an appropriate criterion to establish the remission of papillary thyroid carcinoma.

The three facets of the SARS-CoV-2 pandemic during the first two waves in the northern, central, and southern Italy.

BACKGROUND: There is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions. OBJECTIVE: This study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions. METHODS: An observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes. RESULTS: Male patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area. CONCLUSIONS: Statistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings.

COVID-induced thyroid autoimmunity.

Breakdown of self-tolerance to thyroid antigens (thyroperoxidase, thyroglobulin and the thyrotropin-receptor) is the driver of thyroid autoimmunity. It has been suggested that infectious disease might trigger autoimmune thyroid disease (AITD). Involvement of the thyroid has been reported during severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection, in the form of subacute thyroiditis in subjects with mild coronavirus disease 19 disease (COVID-19) and of painless, destructive thyroiditis in hospitalized patients with severe infection. In addition, cases of AITD, both Graves' disease (GD) and Hashimoto's thyroiditis (HT), have been reported in association with (SARS-CoV-2) infection. In this review, we focus on the relationship between SARS-CoV-2 infection and occurrence of AITD. Nine cases of GD strictly related to SARS-CoV-2 infection and only three cases of HT associated to COVID-19 infection have been reported. No study has demonstrated a role of AITD as a risk factor for a poor prognosis of COVID-19 infection.

Steroid treatment in the management of destructive thyrotoxicosis induced by PD1 blockade.

Objective: Destructive thyroiditis is the most common endocrine immune-related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless, in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. The aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status. Methods: We conducted a retrospective study, comparing the course of thyrotoxicosis of four patients treated with oral prednisone at the dosage of 25 mg/day (tapered to discontinuation in 3 weeks) and an enlarged thyroid volume to that of eight patients with similar thyroid volume who were left untreated. Results: The levels of thyroid hormones were lower in subjects treated compared to those untreated at time of 7, 14, 21, 28, 35, 42, 60 and 90 days (P < 0.05 at each time). The time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 120 days in untreated patients (P < 0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the two groups (4/4 in the steroid group vs 7/8 in the untreated group, P = 0.74) and no difference was found in tumor progression (P = 0.89). Conclusions: Our preliminary data suggest that in patients with a poor performance status experiencing a severe destructive thyrotoxicosis induced by PD-1 blockade, a short period of administration of oral prednisone is effective in obtaining a quick reduction of the levels of thyroid hormones.

Analysis of a Cooperation and Interventional Model in Humanitarian Medicine.

Background: Every year, around 15 million children, in developing countries, die or develop life-long disabilities because of congenital cardiac diseases. In this report we measure the effect of a pediatric cardiac surgery humanitarian project on the health of the individual and on the potential influence this has on the countries economy and its growing health services. Methods: We collected and analyzed data from the Italian NGO, Mission Bambini's database, including all congenital cardiac missions undertaken in Cambodia between 2012 and 2019. DALY's (Disability Adjusted Life Years) saved by the humanitarian mission were estimated and used to reflect on the impact this had on the populations economy. Progression in the local medical teams skills emulated the advancements made in the health sector of the region. Results: Between 2012 and 2019, 128 patients underwent a congenital cardiac operation at Angkor Hospital for Children at Siem Reap, Cambodia. The median age was 6 years. The majority of the pathologies included VSD, TOF, ASD. The mean Aristotle's Complexity Score was 6. Post-operative mortality was 0.8% (1/128). The cost-effectiveness analysis identified 5.360 DALY's saved by surgery. The competency of the local team was progressive with them being able to handle more complex cases on subsequent missions. Conclusion: In developing Countries, performing congenital cardiac surgery cases can be carried out successfully with improvement in both the economy and the health system of the country by increasing the years and the quality of life of the working population and developing the expertise of the regional team.

Subacute Thyroiditis During the SARS-CoV-2 Pandemic.

CONTEXT: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been related to subacute thyroiditis (SAT). OBJECTIVE: We compared SAT cases during the SARS-CoV-2 pandemic to those observed in the previous years. METHODS: A cross-sectional, retrospective study was conducted at the Endocrinology Unit of University Hospital of Pisa, Italy. We included all patients observed from January 2016 to December 2020 because of an untreated SAT, who had developed the disease within 15 days prior to the visit. SAT cases from 2016 to 2019 (N = 152) are referred to as pre-SARS-CoV-2, while 2020 SAT patients are classified as pos-SARS-CoV-2 (N = 18) or neg-SARS-CoV-2 (N = 28), according to positive or negative SARS-CoV-2 testing performed up to 45 days from SAT onset. RESULTS: While during 2016-2019, most SAT cases were observed in the third quarter, in 2020, 2 peaks were seen, superimposable to the SARS-CoV-2 outbreaks in the second and the fourth quarters. In the second and fourth quarters of 2020, we observed higher levels of free thyroxine (FT4), C-reactive protein (CRP), and thyroglobulin (Tg) compared with the same quarters of the years 2016-2019. Pos-SARS-CoV-2 patients had higher FT4 (28.4 vs 24.1 nmol/L), CRP (8.5 vs 3.6 mg/L), and Tg (155 vs 60 µg/L) (P < 0.05 for all) and more frequently had hypothyroidism (13/15 vs 30/152 at 3 months) (P < 0.001) than pre-SARS-CoV-2 patients. Neg-SARS-CoV-2 patients showed a clinical picture intermediate between the other 2 groups. CONCLUSION: The SARS-CoV-2 pandemic has caused a shift in the annual timing and severity of SAT cases.

Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade.

CONTEXT: Thyrotoxicosis is a common immune-related adverse event in patients treated with programmed cell death protein-1 (PD1) or programmed cell death protein ligand-1 (PD-L1) blockade. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy, is lacking, as are data on response to treatment and follow-up. OBJECTIVE: The aim of this study was to better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and treatment. METHODS: We conducted a retrospective study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis on PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, 99mtechnecium scintiscan, and longitudinal thyroid function tests. RESULTS: Five patients had normal or increased scintigraphic uptake (Sci+), no serum antibodies against the thyrotropin receptor, and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N = 9) or euthyroidism (N = 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P = .04). Among Sci- individuals, a larger thyroid volume was associated with a longer time to remission (P < .05). Methimazole (MMI) was effective only in Sci+ individuals (P < .05). CONCLUSION: Administration of PD1- or PD-L1-blocking antibodies may induce 2 different forms of thyrotoxicosis that appear similar in clinical severity at onset: a type 1 characterized by persistent hyperthyroidism that requires treatment with MMI, and a type 2, characterized by destructive and transient thyrotoxicosis that evolves to hypothyroidism or euthyroidism. Thyroid scintigraphy and ultrasound help in differentiating and managing these 2 forms of iatrogenic thyrotoxicosis.

Mission Bambini and the "Children's Heart Program": The Challenge of Congenital Heart Disease Among Emergency and Education.

Congenital heart disease is defined as abnormality in the cardiovascular structure or function that is present at birth and it is the most common cause of congenital anomalies. Approximately 90% of more than 1,000,000 children born per year with congenital heart disease worldwide receive suboptimal care or have no access to care at all. Furthermore, the mortality is likely underreported in Low-and Middle-Income Countries. Mission Bambini Foundation is an Italian NGO founded in 2000, aiming at "helping and supporting children who are poor, sick, without education or physically and morally abused" in Italy and worldwide. In 20 years, through 1.700 projects, 1.4 million children have been supported in 75 Countries. In 2005, Mission Bambini launched the "Children's Heart Program," based on long-term partnerships and on medical/surgical volunteering, in order to provide multidisciplinary education and training and technical support.

Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series.

CONTEXT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide and the pandemic is still spreading. After the first case we reported, we observed 4 additional cases of subacute thyroiditis (SAT) related to SARS-CoV-2 infection. OBJECTIVES: The objective of this work is to describe additional cases of SAT associated with SARS-CoV-2 infection to alert physicians that SAT may be a manifestation of SARS-CoV-2 infection. METHODS: We describe clinical, biochemical, and imaging features of 4 patients with SAT related to SARS-CoV-2 infection. RESULTS: All patients were female (age, 29-46 years). SAT developed 16 to 36 days after the resolution of coronavirus disease 2019 (COVID-19). Neck pain radiated to the jaw and palpitations were the main presenting symptoms and were associated with fever and asthenia. One patient was hospitalized because of atrial fibrillation. Thyroid function tests (available for 3 individuals) were suggestive of destructive thyroiditis, and inflammatory markers were high. At neck ultrasound the thyroid was enlarged, with diffuse and bilateral hypoechoic areas and (in 3 patients) absent vascularization at color Doppler. Symptoms disappeared a few days after commencement of treatment (prednisone in 3 patients and ibuprofen in 1). Six weeks after the onset of SAT, all patients were asymptomatic and inflammatory markers had returned to normal range. Two patients were euthyroid, whereas 2 were diagnosed with subclinical hypothyroidism. CONCLUSIONS: SAT may be an underestimated manifestation of COVID-19. Clinicians should keep in mind the possible occurrence of SAT during and after SARS-CoV-2 infection.

Subacute Thyroiditis After Sars-COV-2 Infection.

CONTEXT: Subacute thyroiditis (SAT) is a thyroid disease of viral or postviral origin. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly worldwide and Italy has been severely affected by this outbreak. OBJECTIVES: The objective of this work is to report the first case of SAT related to SARS-CoV-2 infection. METHODS: We describe the clinical, laboratory, and imaging features of an 18-year-old woman who came to our attention for fever, neck pain radiated to the jaw, and palpitations occurring 15 days after a SARS-CoV-2-positive oropharyngeal swab. Coronavirus disease 2019 (COVID-19) had been mild and the patient had completely recovered in a few days. RESULTS: At physical examination the patient presented with a slightly increased heart rate and a painful and enlarged thyroid on palpation. At laboratory exams free thyroxine and free triiodothyronine were high, thyrotropin undetectable, and inflammatory markers and white blood cell count elevated. Bilateral and diffuse hypoechoic areas were detected at neck ultrasound. One month earlier, thyroid function and imaging both were normal. We diagnosed SAT and the patient started prednisone. Neck pain and fever recovered within 2 days and the remaining symptoms within 1 week. Thyroid function and inflammatory markers normalized in 40 days. CONCLUSIONS: We report the first case of SAT after a SARS-CoV-2 infection. We alert clinicians to additional and unreported clinical manifestations associated with COVID-19.

Graves' Disease Induced by Immune Checkpoint Inhibitors: A Case Report and Review of the Literature.

INTRODUCTION: In the last few years, immune checkpoint inhibitors (ICPis) have become a common treatment of cancer. ICPis are associated with peculiar immune side effects, termed immune-related adverse events (irAEs). Thyroid disfunction is a common irAE, but clinical manifestation, severity, and pathogenesis can be variable. While destructive thyroiditis and hypothyroidism are the most common thyroid irAEs induced by ICPis, autoimmune hyperthyroidism (Graves' disease) is rare. We describe a case of a Graves' disease induced by anti-PD-1 therapy and we review the previous reports on this issue. CASE PRESENTATION: A 51-year-old man developed an overt autoimmune hyperthyroidism 2 months after he had started nivolumab (anti-PD-1) therapy for a metastatic non-small cell lung cancer. Although TSH-receptor autoantibodies (TRAb) were negative, the persistence of hyperthyroidism, the hypervascular pattern at thyroid ultrasound, and the high uptake at thyroid scintigraphy were all features suggestive of Graves' disease. Methimazole was started with the prompt restoration of euthyroidism. TRAb remained undetectable during the entire follow-up. CONCLUSIONS: Autoimmune hyperthyroidism can be induced by anti-PD-1 treatment. TRAb were negative in both cases of nivolumab-induced Graves' disease described to date. A correct differential diagnosis between destructive thyroiditis and autoimmune hyperthyroidism is crucial for the appropriate treatment.

Clinical heterogeneity of hypophysitis secondary to PD-1/PD-L1 blockade: insights from four cases.

SUMMARY: Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy. LEARNING POINTS: PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade. Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities. Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease. PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases.

Lenvatinib Administered via Nasogastric Tube in Poorly Differentiated Thyroid Cancer.

BACKGROUND: The tyrosine kinase inhibitors (TKIs) are indicated for the treatment of locally advanced or metastatic progressive thyroid carcinoma (CDT), refractory to radioactive iodine. The following report describes the efficacy of lenvatinib administered through a nose-gastric tube (SNG) in a patient affected with a poorly differentiated thyroid carcinoma (PDTC) which determined a stenosis of the esophagus. MATERIAL AND METHODS: A patient was followed up for papillary thyroid carcinoma follicular variant (T3NxMx), subjected to total thyroidectomy and treated with iodine-131 radio metabolic therapy. Two years after surgery, following the onset of dysphonia and dysphagia, patient was submitted to a computed tomography (CT) scan of the neck that showed the presence of a lesion of 6 × 2.5 × 3.5 cm, which determined trachea deviation and cervical esophagus compression. The biopsy indicated the presence of PDTC, triggering tracheal lumen reduction and sub-stenosis of the cervical esophagus for an ab-extrinsic compression. A nose-gastric tube (SNG) was placed and lenvatinib was started at a dose of 20 mg/day, administered via this probe after opening the capsules and diluting the drug in 10 ml of saline solution. RESULTS: One month later, CT showed a significant cervical lesion reduction. Bronchoscopy confirmed tracheal infiltration, but the residual caliber was improved from 50% to 75%. At the esophagogastroduodenoscopy (EGDS), the sub stenosis of the cervical esophagus was no longer appreciated; however, a double perforation of the esophagus was found, without fistula. CONCLUSION: Lenvatinib therapy is effective also when administered via SNG. Our result is of particular relevance in the management of thyroid cancer patients, especially in the presence of subjects unable to swallow. Further studies are needed to validate the administration of lenvatinib by SNG, in order to extend the indications to this alternative administration way, beside the oral one.

Echocardiographic predictors of reoperation for subaortic stenosis in children and adults.

OBJECTIVES: Subaortic stenosis (SAS) can present as various types of obstruction of the left ventricular outflow tract (LVOT) below the level of the aortic valve. Even though corrective surgery has been identified as the most effective treatment, SAS more frequently reoccurs requiring reoperation in a significant proportion of the patients. Previous studies have focused on predictors of recurrence in various subgroups of patients with SAS, but rarely in the overall population of patients with SAS. The aim of this study was to determine the predictors of recurrence of SAS after initial corrective surgery. METHODS: Patients from the database of the Congenital Cardiology Department of the University Hospital of Southampton with significant SAS requiring corrective surgery were included in the study. Data retrieved were obtained and used to determine the predictors of SAS recurrence after the initial corrective surgery. RESULTS: Eighty-two patients (paediatric, n = 72 and adult, n = 10) who underwent initial successful resection were included in the analysis. Thirty patients required reoperation for recurrent SAS. These were significantly younger (median age 3.0 vs 6.7 years, P = 0.002). The recurrence of SAS was more common in patients with an interrupted aortic arch (23.3% vs 3.8%, P = 0.010) and unfavourable left ventricle geometry (43.3% vs 7.6%, P < 0.001), with steeper aortoseptal angle (131.0° ± 8.7° vs 136.1° ± 8.6°, P = 0.030), shorter distance between the point of obstruction of the LVOT and the aortic valve annulus in systole and diastole (median 4.30 vs 5.90 mm, P = 0.003 and 3.65 vs 4.95 mm, P = 0.006, respectively) and in those who had higher residual peak and mean LVOT gradients postoperatively (29.3 ± 16.0 vs 19.8 ± 10.7 mmHg, P = 0.006 and 15.9 ± 8.3 vs 10.1 ± 5.8 mmHg, P = 0.002, respectively). Overall, the presence of an interrupted aortic arch [odds ratio (OR) 10.34, 95% confidence interval (CI) 1.46-73.25; P < 0.019] and unfavourable left ventricle geometry (OR 10.42, 95% CI 1.86-58.39; P < 0.008) could independently predict reoperation for SAS after initial successful resection. CONCLUSIONS: Patients who have initial corrective surgery for SAS at a younger age, unfavourable left ventricle geometry, an interrupted aortic arch and higher early postoperative LVOT gradients are more likely to have recurrent SAS requiring reoperation.

Primary surgical repair of tetralogy of Fallot at under three months of age.

Background Classical management of small infants with tetralogy of Fallot has involved placement of a Blalock-Taussig shunt followed later by complete repair, rather than primary complete repair which is the strategy adopted in larger infants. Some advantages of early complete repair compared to a staged strategy have been shown. We sought to review our institutional outcomes. Methods Patients under 3-months old undergoing complete surgical repair of tetralogy of Fallot in our institution between 2005 and 2015 were retrospectively reviewed and compared with an older control group matched by anatomical diagnosis and outflow tract intervention. Results Fourteen index cases (group A) and 14 controls (group B) were identified. At surgery, the median age was 43 days and weight 4.2 kg in group A, and 130 days and 6.1 kg in group B. Nine of 14 in group A were admitted for surgery as emergencies compared to none in group B. Peak inotrope score (22.3 vs. 12.8, p = 0.02) and intensive care unit stay (4.4 vs. 2.6 days, p = 0.02) were higher in group A. Bypass and crossclamp times, duration of intubation, and total length of stay did not differ. Conclusions We conclude that although babies undergoing early repair of tetralogy of Fallot have an increased need for intensive care support in the early postoperative period, the total length of stay is not prolonged despite more emergency admissions. As it is known that early repair may reduce long-term morbidity, we propose consideration of earlier complete repair of tetralogy of Fallot.

Hybrid strategies for high-risk non-hypoplastic left heart syndrome patients.

Single-stage repair of complex cardiac abnormalities in high-risk neonates presents formidable challenges. The majority of hybrid strategies involving bilateral pulmonary artery banding (bPAB) with or without patent ductus arteriosus (PDA) stenting is described in the setting of hypoplastic left heart syndrome. We present a series of cases describing two-stage repair with initial palliative hybrid procedures involving bPAB with or without PDA stenting. This allows weight gain and stabilization of circulation before complete repair, provides good results, and may overcome risk factors associated with single-stage repair in neonates.