Thyroglobulin is a poor predictor of differentiated thyroid cancer in patients who undergo surgery for thyroid nodular diseases.

OBJECTIVES: Thyroglobulin, produced exclusively by thyroid follicular cells, serves as a specific tumor marker for the follow-up of differentiated thyroid cancer (DTC) patients after thyroidectomy. However, its role as a predictor of malignancy in patients with thyroid nodules is controversial. We assessed the potential role of preoperative serum thyroglobulin concentration to predict DTC in patients without a preoperative diagnosis of malignancy who underwent partial or total thyroidectomy. METHODS: This retrospective study included patients with a preoperative diagnosis of benign multinodular goiter (MNG) or a thyroid nodule with indeterminate cytology (INC) (Bethesda system categories III/IV) who underwent partial or total thyroidectomy between January 2014 and May 2019. We compared the patients' demographic, clinical, imaging, and biochemical data according to their final diagnosis: DTC or benign thyroid nodular disease. Further statistical analysis included odds ratio calculation and receiver operating characteristic (ROC) curve analysis. RESULTS: Of 131 patients who met inclusion and exclusion criteria, the indication for surgery was benign MNG in 69 patients and a thyroid nodule with INC in 62 patients. A final diagnosis of DTC was reported in 18 of the 69 benign MNG patients (26%) and in 30 of the 62 thyroid nodule with INC patients (48%). The preoperative measurements of nodule diameter and serum thyroid-stimulating hormone and thyroglobulin concentrations did not significantly differ between patients with a final diagnosis of DTC and those with benign histology. CONCLUSIONS: Preoperative serum thyroglobulin alone is insufficient to differentiate between malignant and benign thyroid nodular disease.

Rates of Malignancy in Cytology Indeterminate Thyroid Nodules: A Single Center Surgical Series.

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.

Safety and long-term efficacy of tonsillectomy versus subtotal tonsillectomy in children with sleep disordered breathing.

OBJECTIVES: to compare safety and long-term symptoms after TE compared to Subtotal Tonsillectomy (STT). METHODS: A retrospective review data of 412 patients, one to twelve years old that underwent either TE or STT, as treatment for sleep disorder breathing, at two different medical centers. Symptoms were assessed by a questionnaire 3-5 years post-surgery. Additionally, data regarding immediate post-operative symptoms and complications were also collected. RESULTS: Long-term symptoms score was significantly lower in the TE group: 1.585 (±1.719) compared to 1.967 (±1.815) in the STT group (p = 0.033); 51.3% of patients in the ST group presented long-term SDB symptoms, compared to 40.6% in the TE group (p = 0.035); The main difference between the groups was snoring as 49% of the STT group suffered from snoring, versus 28.9% in the TE group (p < 0.001). CONCLUSIONS: TE showed an advantage over STT in resolving snoring in the long term.

Assessment of parathyroid gland cellularity by digital slide analysis.

BACKGROUND: Computer-aided examination of digital tissue images has attracted attention in recent years. Application in the field of parathyroid pathology has not been studied previously. It holds a potential to assist in the examination of parathyroid gland adenoma or hyperplasia. OBJECTIVES: To explore parathyroid cell detection of slide images by digital tissue analysis and compare the results to standard human processing. METHODS: 47 incisional biopsies of healthy appearing parathyroid glands were evaluated for their cellularity level. First, by the standard examination using microscopy by three independent pathologists. We compared the mean cellularity grading of the pathologists to the output of a computerized cell detection software. RESULTS: A disagreement was found between the standard human cellularity grading and the digital analysis output. However, the digital analysis reaches a 94% specificity and 48% sensitivity to predict high cellularity (>60% parenchymal cells). CONCLUSIONS: Digital analysis of parathyroid tissue can be used as a tool for hypercellularity elimination, therefore assisting in the diagnosis of parathyroid cell hyperplasia. Additional studies using more advanced algorithms are necessary for further precision enhancement.

Treatment Modality and Second Primary Tumors of the Head and Neck.

INTRODUCTION: Second primary tumors (SPTs) in head and neck cancer are thought to occur from premalignant lesions that are present at the time of the primary tumor diagnosis. The association of the modality used to treat the primary lesion with SPT occurrence is not clear. OBJECTIVE: The aim of the study was to assess the incidence of SPTs in patients with head and neck malignancies, according to treatment modality. METHODS: We conducted a retrospective cohort study. All patients who were treated at Soroka Medical Center between 2000 and 2013 for a head and neck squamous cell carcinoma were assessed. Data analysis included tumor site of the primary and second primary and treatment modality of the primary tumor. In addition, demographics as well as habits were recorded as well. RESULTS: Of the 184 patients included in the cohort, SPT developed in 31 patients (17%) with a median time to diagnosis of 4.3 years. Smoking was reported in 74% of those with SPT and 78% of those without. The most common site for SPT was the lungs, with 13 cases, 42% of the total SPTs. Among patients who developed an SPT, for 12 of those with an index tumor in the oral cavity or oro-hypopharynx, 8 (67%) developed an SPT in the same location; for 18 of those with an index tumor in the larynx, 11 (61%) developed a SPT in the lungs and bronchi (p = 0.001). On multivariate analysis, the treatment modality used was not found to be associated with the occurrence of SPTs and the radiotherapy showed no protective or harmful effect (HR 0.64 p = 0.24). CONCLUSION: Treatment modality used for head and neck cancer does not seem to be associated with the occurrence of SPTs.

Trauma-induced vestibular dysfunction: Possible functional repair under α1-antitrypsin-rich conditions.

Transient vestibular organ deafferentation, such that is caused by traumatic tissue injury, is presently addressed by corticosteroid therapy. However, restoration of neurophysiological properties is rarely achieved. Here, it was hypothesized that the tissue-protective attributes of α1-antityrpsin (AAT) may promote restoration of neuronal function. Inner ear injury was inflicted by unilateral labyrinthotomy in wild-type mice and in mice overexpressing human AAT. A 2-week-long assessment of vestibular signs followed. All animals responded with peak vestibular dysfunction scores within 4 h after local trauma. While wild-type animals displayed partial or no recovery across 7 days post-injury, AAT-rich group exhibited early recovery: from behavioral score 9-out-of-9 at peak to 4.8 ±â€¯0.44 (mean ±â€¯SD) within 8 h from injury, a time when wild-type mice scored 8.6 ±â€¯0.54 (p < 0.0001), and from vestibular score 15-out-of-15 to 7.8 ±â€¯2.2 within 24 h, when wild-type mice scored 13.0 ±â€¯2.0 (p < 0.01). Thus, recovery and functional normalisation of an injured vestibular compartment is achievable without corticosteroid therapy; expedited tissue repair processes appear to result from elevated circulating AAT levels. This study lays the foundation for exploring the molecular and cellular mediators of AAT within the repair processes of the delicate microscopic structures of the vestibular end organ.

Limitations of ultrasound in predicting bilaterality vs unilaterality of well-differentiated carcinoma of the thyroid.

PURPOSE: The purpose of this study is to assess the efficacy of ultrasonography in the differentiation of a bilateral and a unilateral WDTC to help physicians decide on performing a total or a partial thyroidectomy. MATERIALS AND METHODS: Retrospective chart review of all patients diagnosed with papillary thyroid carcinoma following a total thyroidectomy or a complete thyroidectomy between January 2013 and December 2015 at the Department of Otorhinolaryngology and Head and Neck Surgery in Soroka University Medical Center in southern Israel. The preoperative ultrasound images of the thyroid were compared to the final pathology in the contralateral lobe. RESULTS: Seventy seven patients (77) were included in this study, There was no correlation between the sonography in the contralateral lobe and the malignancy on that side (p = 0.479). US had a 39% false negative rate and 69% false positive rate. CONCLUSION: The patients with a well-differentiated carcinoma of the thyroid, a benign nodule detected sonographically in the contralateral lobe should not bear a high weight in decision making regarding the extent of surgery.

Endogenous α1-antitrypsin levels in the perilymphatic fluid correlates with severity of hearing loss.

OBJECTIVES: To determine the levels of endogenous α1-antitrypsin in the perilymph of patients undergoing cochlear implant (CI), and its reverse association with the severity of hearing loss. STUDY DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study includes 38 patients undergoing CI surgery, 11 patients diagnosed with congenital deafness and 27 non-congenital deafness, eight patients diagnosed with moderate hearing loss (N = 8; PTA = 70 dB), severe hearing loss (N = 11; PTA 70-90 dB) and profound hearing loss (N = 19; PTA > 90 dB). MAIN OUTCOME AND MEASURE: 1 to 12 µL perilymphatic fluids were collected by micropipette. α1-antitrypsin levels were determined, and current and historic audiological parameters were obtained. RESULTS: The congenital and non-congenital group exhibited AAT concentrations of 2.5 ± 1.9 × 106 LFQ and 3.2 ± 1.2 × 106 LFQ, respectively (mean ± SD; P = .38). Mean levels of α1-antitrypsin in the perilymph fluid within the moderate group was 3.64 × 106  ± 2.1 × 106 LFQ vs 3.5 × 106  ± 1.2 × 106 in severe hearing loss (P = .81) and 2.4 × 106  ± 1.1 × 106 LFQ in the profound hearings loss group (P = .06). The difference in levels of AAT in samples from the severe hearings loss group vs the profound hearings loss group reached statistical significance (P = .04). CONCLUSION: Insufficiency in α1-antitrypsin levels in the perilymph fluid of the inner ear appears to display a relationship with the severity of hearing loss. The prospect of introducing clinical-grade plasma-purified α1-antitrypsin directly onto the site of cochlear injury deserves thorough investigation.

MET activation confers resistance to cetuximab, and prevents HER2 and HER3 upregulation in head and neck cancer.

An understanding of the mechanisms underlying acquired resistance to cetuximab is urgently needed to improve cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Here, we present a clinical observation that MET pathway activation constitutes the mechanism of acquired resistance to cetuximab in a patient with HNSCC. Specifically, RNA sequencing and mass spectrometry analysis of cetuximab-sensitive (CetuxSen ) and cetuximab-resistant (CetuxRes ) tumors indicated MET amplification and overexpression in the CetuxRes tumor compared to the CetuxSen lesion. Stimulation of MET in HNSCC cell lines was sufficient to reactivate the MAPK pathway and to confer resistance to cetuximab in vitro and in vivo. In addition to the direct role of MET in reactivation of the MAPK pathway, MET stimulation abrogates the well-known cetuximab-induced compensatory feedback loop of HER2/HER3 expression. Mechanistically, we showed that the overexpression of HER2 and HER3 following cetuximab treatment is mediated by the ETS homologous transcription factor (EHF), and is suppressed by MET/MAPK pathway activation. Collectively, our findings indicate that evaluation of MET and HER2/HER3 in response to cetuximab in HNSCC patients can provide the rationale of successive line of treatment.

Assessment of the Association Between Post-tonsillectomy Hemorrhage and Weather Conditions.

BACKGROUND: The most common complication after tonsillectomy is bleeding. We investigated whether performing the procedure during the summer or the winter affects the bleeding rate. OBJECTIVES: To investigate whether there is an association between meteorological conditions and the occurrence of post-tonsillectomy hemorrhage (PTH) in the southern Israel Negev region. METHODS: All patients who underwent tonsillectomy from 2001-2013 at the Soroka Medical Center were included. We collected patient demographic data and indications for surgery. Meteorological data were obtained from a weather station operated by the Israel Ministry of Environmental Protection. RESULTS: Of 4438 patients who underwent tonsillectomy, with or without adenoidectomy, 432 (9.73%) experienced hemorrhage. Patients who suffered from PTH were significantly older: median age 9.61 years vs.4.7 years, P < 0.0001. When comparing patients without PTH to those who bled within 0-3 days after surgery, there was a higher risk for bleeding during the warmer seasons: relative risk (RR) 1.38, 95% confidence interval ([95%CI] 1.07-1.77), RR 1.45 (95%CI 1.17-1.80), and 1.62 (95%CI 1.27-2.06) comparing the winter to spring, summer, and fall, respectively. A statistically significant positive association was also found with the average temperature on the day of surgery. Bleeding more than 3 days after surgery was less likely in summer: RR 0.82, 95%CI 0.69-0.97. We found no association with temperature on the day of surgery and PTH after postoperative day 3. CONCLUSIONS: Seasonality, and to an extent temperature, seem to play only a minor role in PTH.

Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.

Randomized study comparing inflammatory response after tonsillectomy versus tonsillotomy.

To determine if there was a difference in the inflammatory reaction after tonsil surgery with "traditional" techniques (tonsillectomy and adenoidectomy or TA) compared to partial intracapsular tonsillectomy and adenoidectomy (PITA). DESIGN: Randomized, double-blind study. SETTING: tertiary care academic hospital. Children under the age of 16 years with a diagnosis of obstructive sleep disordered breathing were randomly allocated into three study groups: TA with electrocautery (n = 34), PITA with CO2 laser (n = 30) and PITA with debrider (n = 28). All of the children underwent adenoidectomy with a current at the same surgical procedure. MAIN OUTCOME MEASURE: c-reactive protein level (CRP) was the primary endpoint. In addition, the following were assessed: white blood cells (WBC), neutrophils (NEU), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Pre- and post-procedure measurements were compared between the groups. Parents filled out a questionnaire daily during the first postoperative week assessing pain, swallowing and snoring. CRP levels ascended higher in the PITA groups after surgery (p = 0.023), WBC and NEU showed the same pattern, IL-6 levels were higher in PITA group and there was no difference in TNF-alpha levels between the two types of procedures. Postoperative pain and postoperative hemorrhage were significantly lower in the PITA groups as compared to the TA group (p = 0.01 and 0.048). PITA in comparison to TA is associated with lower morbidity; however, the inflammatory response does not differ significantly in the first 24 h after surgery. Additional long-term studies assessing efficacy of PITA are warranted. LEVEL OF EVIDENCE: Level 1, prospective randomized controlled trial.

Facial Reconstruction of a Mucormycosis Survivor by Free Rectus Abdominis Muscle Flap, Tissue Expansion, and Ocular Prosthesis.

Invasive sinonasal mucormycosis is a rare fungal infection that usually occurs in immunocompromised or diabetic patients, and it is often fatal. The authors present a case of a woman patient suffering from systemic lupus erythematosus and diabetes mellitus treated with prednisone, presenting with a rapidly progressive rhino-orbital-cerebral mucormycosis. She was successfully treated with combined intravenous antifungal therapy and radical debridement followed by complex defect reconstruction with a free vertical rectus abdominis myocutaneous flap, tissue expander, and ophthalmic prosthesis.

Association of reactive oxygen species levels and radioresistance in cancer stem cells.

The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.

Oral Mucoceles in Children--Analysis of 56 New Cases.

BACKGROUND: Mucoceles are common cystic lesions of the oral mucosa. Extravasation mucoceles (EMs) are mainly found in the lower lip of young patients, whereas retention mucoceles (RMs) are usually located in the cheek or palate of older patients. This study was undertaken to more fully characterize the clinicopathologic features of mucoceles in pediatric patients. METHODS: The records of 56 pediatric patients with mucoceles were included in the study. Age, sex, history of trauma, intraoral site, size, and method of treatment were evaluated. Histopathologically the lesions were classified as being EMs or RMs. RESULTS: The age range was 1.5 to 16 years (mean age 11.2 yrs). Of the 56 patients, 24 (43%) were males and 32 (57%) were females, with a male:female ratio of 1:1.33. A history of trauma was recorded in 32 (57%) patients of the lower lip. The intraoral sites were the lower lip (38 [68%]), tongue (10 [18%]), and floor of the mouth (8 [14%]). Of the 56 patients, 44 (79%) were EM and 12 (21%) were ranulas. No RMs were found. Mucoceles ranged from 0.3 to 3.8 cm in diameter (mean 0.9 cm). The treatment of EMs was surgical excision. Cryosurgey, electrosurgery, and carbon dioxide laser were also used. CONCLUSION: In contrast to adults, where EM and RM types can be found, among children all cases are of the EM type. The disparate site and age incidences of EMs and RMs of the oral mucosa suggest that these two types are not related and possibly have a different etiopathogenesis.

Sudden hearing loss with simultaneous posterior semicircular canal BPPV: possible etiology and clinical implications.

OBJECTIVES: The objectives of this study were to describe the clinical course and outcome of patients with sudden sensorineural hearing loss (SSNHL) in conjunction with benign paroxysmal positional vertigo (BPPV), and hypothesize the possible pathophysiology of this entity. STUDY DESIGN: Retrospective study of all patients with evidence of SSNHL with any type of BPPV between 2008 and 2012. SETTINGS: Tertiary care university hospital. SUBJECTS AND METHODS: Five patients aged 56 to 71 were diagnosed with unilateral profound SSNHL and BPPV. Neurotologic examination revealed an ipsilateral torsional, up-beating nystagmus on Dix-Hallpike exam. Severe or profound ipsilateral-sensorineural hearing loss was recognized on audiometry. The rest of the exam was normal; this was in keeping with the diagnosis of SSNHL with ipsilateral posterior semicircular canal BPPV. RESULTS: All patients were treated with a modified Epley maneuver; oral steroids were administered for two weeks. In all cases vertigo resolved and the Dix-Hallpike exam became normal within several weeks. However, the hearing loss remained unchanged in two patients. Magnetic resonance imaging of the head was normal and ENG caloric test demonstrated mild ipsilateral canal paresis in two patients. CONCLUSIONS: 1. Patients with SSNHL and BPPV can have a variable clinical course and outcome. This entity may be quite common, but the diagnosis of BPPV can be missed if a complete neurological physical examination is not performed. 2. Arterial occlusions or selective multiple vascular or neural involvement may explain the pathophysiology of SSNHL with BPPV of the posterior semicircular canal.

Exploring the Interplay of Dataset Size and Imbalance on CNN Performance in Healthcare: Using X-rays to Identify COVID-19 Patients.

INTRODUCTION: Convolutional Neural Network (CNN) systems in healthcare are influenced by unbalanced datasets and varying sizes. This article delves into the impact of dataset size, class imbalance, and their interplay on CNN systems, focusing on the size of the training set versus imbalance-a unique perspective compared to the prevailing literature. Furthermore, it addresses scenarios with more than two classification groups, often overlooked but prevalent in practical settings. METHODS: Initially, a CNN was developed to classify lung diseases using X-ray images, distinguishing between healthy individuals and COVID-19 patients. Later, the model was expanded to include pneumonia patients. To evaluate performance, numerous experiments were conducted with varied data sizes and imbalance ratios for both binary and ternary classifications, measuring various indices to validate the model's efficacy. RESULTS: The study revealed that increasing dataset size positively impacts CNN performance, but this improvement saturates beyond a certain size. A novel finding is that the data balance ratio influences performance more significantly than dataset size. The behavior of three-class classification mirrored that of binary classification, underscoring the importance of balanced datasets for accurate classification. CONCLUSIONS: This study emphasizes the fact that achieving balanced representation in datasets is crucial for optimal CNN performance in healthcare, challenging the conventional focus on dataset size. Balanced datasets improve classification accuracy, both in two-class and three-class scenarios, highlighting the need for data-balancing techniques to improve model reliability and effectiveness. MOTIVATION: Our study is motivated by a scenario with 100 patient samples, offering two options: a balanced dataset with 200 samples and an unbalanced dataset with 500 samples (400 healthy individuals). We aim to provide insights into the optimal choice based on the interplay between dataset size and imbalance, enriching the discourse for stakeholders interested in achieving optimal model performance. LIMITATIONS: Recognizing a single model's generalizability limitations, we assert that further studies on diverse datasets are needed.

Epiglottic abscess as a complication of acute epiglottitis.

OBJECTIVE: An epiglottic abscess is considered a life-threatening medical situation that can cause death by obstruction the upper airways. We describe a 58-year-old man who presented to our hospital with sore throat, dysphagia and dysphonia. MATERIALS AND METHODS: A fiberoptic laryngoscope (FOL) demonstrated beefy red edematous epiglottis with edema extending from the base of the tongue to the aryepiglottic folds and arytenoids. CT scan showed multiple air bubbles inside the swollen epiglottis, in keeping with the diagnosis of necrotizing epiglottic abscess. RESULTS: Under local anesthesia we performed puncture of the abscess at the tip of the epiglottis. He was dismissed 5days from his admission to the hospital after an improvement was noticed in his epiglottis. CONCLUSION: Treatment consists of airway management if needed under anesthesia and draining of the abscess. An IV antibiotics plus corticosteroids should be administrated the moment a suspicion of epiglottitis is present.

Ivabradine for Uncontrolled Sinus Tachycardia in Thyrotoxic Cardiomyopathy - Case Report.

BACKGROUND: Beta-blockers, mainly propranalol, are usually administered to control heart rate in patients with thyrotoxicosis, especially when congestive heart failure presents. However, when thyrotoxicosis is not controlled, heart rate may be difficult to control even with maximal doses of propranolol. This presentation alerts physicians to the possibility of using ivabradine, a selective inhibitor of the sinoatrial pacemaker, for the control of heart rate. CASE PRESENTATION: We present a 37-year-old woman with thyrotoxicosis and congestive heart failure whose heart rate was not controlled with a maximal dose of beta blockers during a thyroid storm. The addition of ivabradine, a selective inhibitor of the sinoatrial pacemaker, controlled her heart rate within 48 hours. CONCLUSION: Ivabradine should be considered in patients with thyrotoxicosis, including those with heart failure, in whom beta blockers are insufficient to control heart rate.

Metastatic neuroblastoma of the mandible: a cytogenetic and molecular genetic study.

Neuroblastoma (NB) jaw metastases are rare. Here, we report on cytogenetic and genetic studies on metastatic NB to the mandible. A 7-year-old boy, with an abdominal neuroblastoma, presented with a mass of the left body of the mandible. Cytogenetic analysis of the original tumor and the mandibular lesion biopsies revealed similar heterogenous subclones with 42 ~ 47,XY,+der(1)(q11 → qter),-2,del(7)(q21.1 → qter),-8,-9,-10,-11,del(11)(q13.3 → qter),-13,-14,-15,-17, + 18-18,der(18)(?),+21,+m1,+m2,+m3,+m4,+m5,+m6,+m7[cp25]. The different markers were identified by SKY analysis. Most of the cells carried 3-6 of these translocations: der(1;21), der(2;9;17), der(2;15;18), der(2;15;Y), der(8;10), der(10;17). Molecular examination using Neuroblastoma MLPA kit (MRC-Holland) revealed gain of 1q25, 1q42, 2q33, 2p23, 2p24 (N-myc), and 21q22, and loss of 11q22, 11q23, 17p13, and 17q11. FISH analysis using N-myc probe showed high amplification levels of N-myc. The cytogenetic and molecular genetic work-ups revealed that the mandibular lesion is a metastasis of the original abdominal tumor and not a second primary caused by the aggressive treatment. Clinical parameters such as : patient's age, site of primary tumor and the mandibular metastasis, together with poor prognosis genetic markers explain the patient's short-term survival.