Thyroid US-guided FNA techniques: A prospective,randomized controlled study.

BACKGROUND: Thyroid nodules are common in the general population. Ultrasonography is the most efficient diagnostic approach to evaluate thyroid nodules. The US FNAC procedure can be performed using either the short axis (perpendicular), or a long axis (parallel) approach to visualize the needle as it is advanced toward the desired nodule. The main aim of this study was to compare the percentage of non-diagnostic results between the long and short axis approach. METHODS: A prospective study that included a randomized controlled trial and was divided into two arms-the short axis and the long axis-was conducted. A total of 245 thyroid nodules were collected through the fine needle aspiration cytology, performed with ultrasound, from march 2021 to march 2022. The patient's demographic information were collected and also nodules characteristics. RESULTS: Of 245 nodules sampled, 122 were sampled with the long axis method, while 123 with the short axis method. There is not significantly less non diagnostic approach with either method compared to the other (11.5 % vs 16.3 % respectively). DISCUSSION: Previous studies came to the conclusion that the long axis method yields fewer non diagnostic samples. This study evaluated the two FNA approaches which were proceeded by the same physician who is expert in both techniques. CONCLUSION: The US FNAC performed in the long axis approach will not produce more conclusive results and less non diagnostic results (Bethesda category 1) than the short axis approach one.

Does acute isolated sphenoidal sinusitis meet the criteria of the recent acute sinusitis guidelines, EPOS2020?

INTRODUCTION: Isolated sphenoidal sinusitis (ISS) is a rare disease with non-specific symptoms and a potential for complications. Diagnosis is made clinically, endoscopically, and with imaging like CT scans or MRIs. This study aimed to evaluate if ISS meets the EPOS 2020 criteria for diagnosing acute rhinosinusitis and if new diagnostic criteria are needed. MATERIALS AND METHODS: The study analyzed 193 charts and examination records from 2000 to 2022 in patients diagnosed with isolated sphenoidal sinusitis at the Ziv Medical Center in Safed, Israel. Of the 193, 57 patients were excluded, and the remaining 136 patients were included in the final analysis. Patients were evaluated using Ear, Nose and Throat (ENT), neurological and sinonasal video endoscopy, radiological findings, demographic data, symptoms and signs, and laboratory results. All these findings were reviewed according to the EPOS 2020 acute sinusitis diagnosis criteria and were analyzed to determine if ISS symptoms and signs fulfilled them. RESULTS: The patients included 40 men and 96 women, ranging in age from 17 to 86 years (mean ± SD, 37 ± 15.2 years). A positive endoscopy and radiography were encountered in 29.4%, and headache was present in 98%; the most common type was retro-orbital headache (31%). The results showed that there is no relationship between the symptoms of isolated sphenoidal sinusitis and the criteria for diagnosing acute sinusitis according to EPOS 2020. CONCLUSION: ISS is an uncommon entity encountered in clinical practice with non-specific symptoms and a potential for complications. Therefore, the condition must be kept in mind by clinicians, and prompt diagnosis and treatment must be initiated. This kind of sinusitis does not fulfill the standard guidelines for acute sinusitis diagnosis criteria.

The "Vestibular Eye Sign"-"VES": a new radiological sign of vestibular neuronitis can help to determine the affected vestibule and support the diagnosis.

INTRODUCTION: Nystagmus is a valuable clinical finding. Although nystagmus is often described by the direction of its quick phases, it is the slow phase that reflects the underlying disorder. The aim of our study was to describe a new radiological diagnostic sign called "Vestibular Eye Sign"-VES. This sign is defined as an eye deviation that correlates with the slow phase of nystagmus (vestibule pathological side), which is seen in acute vestibular neuronitis and can be assessed on a CT head scan. MATERIALS AND METHODS: A total of 1250 patients were diagnosed with vertigo in the Emergency Department at Ziv Medical Center (ED) in Safed, Israel. The data of 315 patients who arrived at the ED between January 2010 and January 2022 were collected, with criteria eligible for the study. Patients were divided into 4 groups: Group A, "pure VN", Group B, "non-VN aetiology", Group C, BPPV patients, and Group D, patients who had a diagnosis of vertigo with unknown aetiology. All groups underwent head CT examination while in the ED. RESULTS: In Group 1, pure vestibular neuritis was diagnosed in 70 (22.2%) patients. Regarding accuracy, VES (Vestibular Eye Sign) was found in 65 patients in group 1 and 8 patients in group 2 and had a sensitivity of 89%, specificity of 75% and a negative predictive value of 99.4% in group 1-pure vestibular neuronitis. CONCLUSION: VN is still a clinical diagnosis, but if the patient undergoes head CT, we suggest using the "Vestibular Eye Sign" as a complementary sign. As per our findings, this is a valuable sign on CT imaging for diagnosing the pathological side of isolated pure VN. It is sensitive to support a diagnosis with a high negative predictive value.

Kaposi sarcoma at the base of the tongue in a renal transplant patient.

Oral Kaposi Sarcoma (OKS) commonly occurs in patients with AIDS. The incidence of Kaposi sarcoma (KS) is greatly increased in renal transplant recipients compared with the general population, with particular prevalence in certain ethnic groups where it can occur in up to 5% of transplant recipients. From them, only 2% can manifest first with OKS.A man in his early 40s, 2 years after kidney transplantation, presented with a reddish-purple hypertrophic ulcerated lesion at the base of the tongue. Cervical ultrasonography revealed enlarged lymph nodes, and pathological examination of biopsies revealed KS. The patient had HIV-negative status. Following an investigation, calcineurin inhibitor treatment was stopped, and an mTOR (mammalian target of rapamycin) inhibitor treatment was started. Fibreoptic examination 3 months after beginning mTOR inhibitor treatment revealed no traces of the disease in the base of the tongue.An isolated oral lesion should not distract clinicians from further systemic investigation for metastatic disease.OKS is a rare but serious complication in kidney transplant patients after receiving calcineurin inhibitor that could result in airway obstruction due to mass effect or bleeding and aspiration.Early diagnosis and management of OKS in a renal transplant patient who received a calcineurin inhibitor carry a good prognosis. OKS can be managed by changing the treatment regime to an mTOR inhibitor followed by radiation therapy. This contrasts with KS treatment in non-renal transplant patients without calcineurin inhibitors who may need treatment using different modalities such as surgery and chemotherapy.We emphasise the importance of this case for nephrologists responsible for patient follow-up after renal transplantation who prescribed calcineurin inhibitors. These patients must be advised that if they feel any physical mass in the tongue, they should immediately seek an examination by an ear, nose and throat specialist. Nephrologists and patients should be aware that these symptoms should not be underestimated.

Ultrasound-Guided Fine Needle Aspiration of Deep Thyroid Nodule: Is There a Correlation between the Nodule's Depth and Nondiagnostic Results?

Objective: To evaluate whether thyroid nodule depth correlates with nondiagnostic results in ultrasound-guided fine needle aspiration cytopathology. Background: Many factors correlate with nondiagnostic ultrasound-guided fine needle aspiration cytology (FNAC) results, including older age, macrocalcification, small-sized nodules, aspirin medication, and cystic portion in more than 50% of the thyroid nodules. However, there are few studies which have examined whether there is a relationship between the depth of nodules and the percentage of nondiagnostic results in cytology (Bethesda category I). We conducted this study in order to investigate if such a correlation exists. Materials and Methods: FNAC was performed on 283 thyroid nodules between January 2019 and December 2020. Cytological analyses of the nodules were reviewed and sorted as nondiagnostic and diagnostic according to the Bethesda score. Patient files and ultra sound (US) scans were reviewed for clinical information (such as age, sex, and ethnic group) and sonographic features of nodules (such as depth, size, cystic portion, type of calcification, and echogenicity) and were compared between the nondiagnostic and diagnostic nodule results. The depth of a nodule was calculated as the shortest distance from the skin to the most superficial border of the nodule in the axial plane, using our medical center's computer program, which allows reviewing all saved shots of the US scan. Results: Age, sex, and ethnicity were not significantly different between the nondiagnostic group and the diagnostic group (p > 0.05). Nodule diameter, cystic portion, calcification, and echogenicity were also not associated with the frequency of nondiagnostic results. The depth of nodules ≥9 mm was correlated with nondiagnostic US-guided FNA cytological results (OR = 2.55, p=0.018). Conclusions: Deep thyroid nodules correlated with nondiagnostic US-guided FNA cytological results. Further studies are needed for optimizing the approach to deep thyroid nodules in order to improve the efficacy of FNA in deep thyroid nodules.

US-guided FNA techniques for thyroid nodules is the short axis better than the long axis?

BACKGROUND: Ultrasound-guided fine needle aspiration cytology (FNAC US) has been proven to be an accurate and efficient tool in thyroid nodule evaluation. Thyroid nodule aspiration can be acquired with either of two techniques: the short axis, in which only the tip of the needle is observed, and the long axis, in which the entire length of the needle is observed. Our retrospective study aimed to compare the adequacy of the two techniques. METHODS: FNAC US was performed in 538 thyroid nodules between January 2019 and December 2021. Data on the technique and the diagnostic accuracy were collected. RESULTS: A total of 273 nodules were aspirated using the long axis technique, and 265 nodules were aspirated using the short axis technique. The diagnostic adequacies of the long axis technique were significantly higher than those of the short axis technique (92 % versus 86 %, respectively, p < 0.025). CONCLUSION: In our study, the long axis technique provided more accurate cytological evaluation than the short axis technique. LEVEL OF EVIDENCE: level 3.

Three Complex alleles associated with N1303K mutation and their molecular consequences.

Cystic Fibrosis (CF) in Arab Mediterranean countries has a different CFTR mutational profile if compared either to Caucasians or in the Arabian Peninsula. The c.3909C>G (N1303K, p.Asn1303Lys) mutation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR). This mutation represents a higher frequency in the Mediterranean countries in association with different polymorphisms or mutations in cis position constituting various complex alleles. N1303K mutation induces many phenotypes, especially pancreatic insufficiency from mild to severe and it is associated in cis with other polymorphisms. The aim of this investigation is therefore to screen complex alleles carrying N1303K mutation among Lebanese, Egyptian and French patients. All exons of the CFTR and their flanking regions were performed by PCR amplification, followed by automated direct DNA sequencing. Two complex alleles are more frequent corresponding to Wild Type and mutated haplotype. Besides that two other very rare complex alleles have been detected, one in Egyptian and French samples, and then another one in Lebanon samples. We have studied their impact on the CFTR mRNA splicing using a minigene strategy. Constructs containing wild-type and mutant CFTR cloned into the pTBNdeI hybride minigene have been expressed in HeLa, HT29 and HEK293 cells. RT-PCR analysis of mRNA using ß-globin-specific primers revealed that N1303K and the polymorphisms associated with cis induce weak abnormal splicing and a modification of the quality and the quantity of CFTR protein. These different associations of identified polymorphisms with N1303K in cis could have an impact on the severity of the disease.

Pembrolizumab as a first line therapy in a patient with extensive mucoepidermoid salivary gland carcinoma. A complete clinical, radiological and pathological response. A very specific case.

BACKGROUND: Patients with advanced salivary gland malignancies (SGCs) have few therapy options. Although results from newly published trials suggest that checkpoint inhibition may be useful in a subgroup of patients, there are no clear criteria for PD-L1 score in SGCs. Chemotherapy benefits were observed to be limited, with a dismal prognosis in unresectable and high-grade SGC. Immunotherapies have demonstrated extraordinary efficacy in a variety of cancers, including non-small cell lung cancer and malignant melanoma. Anti-PD-1 antibody pembrolizumab has been shown to have potent anti-tumor action in a number of clinical trials. CASE PRESENTATION: We report a unique case of advanced high grade mucoepidermoid carcinoma of the parotid salivary gland after Pembrolizumab treatment as a first line therapy. The tumor was downstaged as a result of the pembrolizumab treatment, allowing for a successful surgical excision with no facial nerve sacrifice and no major neoadjuvant treatment adverse effects, and the final specimen pathology was tumor-free. In these types of malignancies, a similar technique resulted in a complete response (CR) radiologically and pathologically has never been discussed before. CONCLUSIONS: In pretreated patients with high-grade salivary gland mucoepidermoid carcinoma, pembrolizumab showed good anticancer activity and provided a clinically, radiologically, and pathological response with a viable treatment choice. More research is needed to bring Pembrolizumab to the front-line of treatment. The time and duration of medication should be compared to the time required for surgery in these investigations.

Complexity of phenotypes induced by p.Asn1303Lys-CFTR correlates with difficulty to rescue and activate this protein.

Cystic Fibrosis is the most common recessive autosomal rare disease found in Caucasian. It is caused by mutations on the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) that encodes for a protein located on the apical membrane of epithelial cells. c.3909C>G (p.Asn1303Lys) is one of the most common worldwide mutations located in nucleotide binding domain 2. The effect of the p.Asn1303Lys mutation on misprocessing was studied by immunofluorescence and western blotting analysis in presence and absence of treatment. To evaluate the functionality of potentially rescued p.Asn1303Lys-CFTR, we assessed the channel activity by radioactive iodide efflux. No recovery of the activity was observed in transfected cultured cells treated with VX-809. Thus, our results suggest that multiple drugs may be needed for the treatment of c.3909C>G patients in order to correct and activate p.Asn1303Lys-CFTR as it shows folding and functional defects.

In cellulo analyses of the p.Val322Ala mutation on the CFTR protein conformation and activity.

Cystic fibrosis is caused by mutations on the Cystic Fibrosis Transmembrane conductance Regulator gene (CFTR). Exonic mutations may have variable effect on the CFTR protein and may alter the normal localization of CFTR on the apical membrane of epithelial cells or/and its function as a chloride channel. Identifying the effect of a missense mutation can be a first step in helping the medical counseling and the therapeutic strategies. In this study, the effect of the c.965T>C exon 8 mutation that induces a valine-to-alanine substitution (p.Val322Ala) into the fifth helix of the first membrane spanning domain was determined by in silico and in cellulo analyses. The confocal microscopy analyses and functionality test showed, in the tested cell line, that this mutation should have no impact on the function of the p.Val322Ala-CFTR protein. However, regarding the importance of this Val322 amino acid in the CFTR protein, precautions and individual follow-up are still required when c.965T>C if associated with other mutation(s).

N1303K (c.3909C>G) mutation and splicing: implication of its c.[744-33GATT(6); 869+11C>T] complex allele in CFTR exon 7 aberrant splicing.

Cystic Fibrosis is the most common recessive autosomal rare disease found in Caucasians. It is caused by mutations on the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) that encodes a protein located on the apical membrane of epithelial cells. c.3909C>G (p.Asn1303Lys, old nomenclature: N1303K) is one of the most common worldwide mutations. This mutation has been found at high frequencies in the Mediterranean countries with the highest frequency in the Lebanese population. Therefore, on the genetic level, we conducted a complete CFTR gene screening on c.3909C>G Lebanese patients. The complex allele c.[744-33GATT(6); 869+11C>T] was always associated with the c.3909C>G mutation in cis in the Lebanese population. In cellulo splicing studies, realized by hybrid minigene constructs, revealed no impact of the c.3909C>G mutation on the splicing process, whereas the associated complex allele induces minor exon skipping.

Multi-physiopathological consequences of the c.1392G>T CFTR mutation revealed by clinical and cellular investigations.

This study combines a clinical approach and multiple level cellular analyses to determine the physiopathological consequences of the c.1392G>T (p.Lys464Asn) CFTR exon 10 mutation, detected in a CF patient with a frameshift deletion in trans and a TG(11)T(5) in cis. Minigene experiment, with different TG(m)T(n) alleles, and nasal cell mRNA extracts were used to study the impact of c.1392G>T on splicing in both in cellulo and in vivo studies. The processing and localization of p.Lys464Asn protein were evaluated, in cellulo, by western blotting analyses and confocal microscopy. Clinical and channel exploration tests were performed on the patient to determine the exact CF phenotype profile and the CFTR chloride transport activity. c.1392G>T affects exon 10 splicing by inducing its complete deletion and encoding a frameshift transcript. The polymorphism TG(11)T(5) aggravates the effects of this mutation on aberrant splicing. Analysis of mRNA obtained from parental airway epithelial cells confirmed these in cellulo results. At the protein level the p.Lys464Asn protein showed neither maturated form nor membrane localization. Furthermore, the in vivo channel tests confirmed the absence of CFTR activity. Thus, the c.1392G>T mutation alone or in association with the TG repeats and the poly T tract revealed obvious impacts on splicing and CFTR protein processing and functionality. The c.[T(5); 1392G>T] complex allele contributes to the CF phenotype by affecting splicing and inducing a severe misprocessing defect. These results demonstrate that the classical CFTR mutations classification is not sufficient: in vivo and in cellulo studies of a possible complex allele in a patient are required to provide correct CFTR mutation classification, adequate medical counseling, and adapted therapeutic strategies.