A right-handed signalling pathway drives heart looping in vertebrates.

Most animals show external bilateral symmetry, which hinders the observation of multiple internal left-right (L/R) asymmetries that are fundamental to organ packaging and function. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand side by the epithelial-mesenchymal transition (EMT) inducer Snail1 (refs 3, 4). Despite some existing evidence, it remains unclear whether an equivalent instructive pathway provides right-hand-specific information to the embryo. Here we show that, in zebrafish, BMP mediates the L/R asymmetric activation of another EMT inducer, Prrx1a, in the lateral plate mesoderm with higher levels on the right. Prrx1a drives L/R differential cell movements towards the midline, leading to a leftward displacement of the cardiac posterior pole through an actomyosin-dependent mechanism. Downregulation of Prrx1a prevents heart looping and leads to mesocardia. Two parallel and mutually repressed pathways, respectively driven by Nodal and BMP on the left and right lateral plate mesoderm, converge on the asymmetric activation of the transcription factors Pitx2 and Prrx1, which integrate left and right information to govern heart morphogenesis. This mechanism is conserved in the chicken embryo, and in the mouse SNAIL1 acts in a similar manner to Prrx1a in zebrafish and PRRX1 in the chick. Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates.

Inflammatory complications of vocal fold injection with hyaluronic acid: a multiinstitutional study

Background/aim: This study aimed to assess the inflammatory adverse reactions of vocal fold injection laryngoplasty with hyaluronic acid. Materials and methods: This study was a retrospective chart review of patients who underwent vocal fold injection augmentation with HA injection from January 2005 to September 2016 in nine different institutions. Demographic data, indication for injection, injection techniques, types of injection material, settings of procedure, and complications were reviewed. The types of complication, onset time, and management of complications were also noted. Results: In all, 467 patients were identified. The majority of patients had been injected under general anesthesia (n = 382, 84.7%). For injection material, two different types of hyaluronic acid were used: hyaluronic acid alone or hyaluronic acid with dextranomer. Complications occurred in nine patients (1.9%). The majority of complications were inflammatory reactions (n = 7, 1.47%). Main symptoms were dysphonia and/or dyspnea with an onset of 0 h to 3 weeks after the hyaluronic acid injection. Three patients were hospitalized, one of which was also intubated and observed in the intensive care unit for 24 h. Systemic steroids and antibiotics were the main medical treatment in the majority of cases. There was no statistical difference in complication rates between patients who received hyaluronic acid and those who received hyaluronic acid with dextranomer (P = 0.220). Conclusion: Hyaluronic acid can be considered as a safe substance for the injection of vocal folds with a low risk of inflammatory reaction.

Non-epithelial tumors of the larynx: case series of 12 years.

PURPOSE: Laryngeal neoplasms are almost always epithelial in origin and squamous cell carcinoma is the most common tumor of the larynx. Non-epithelial tumors make a small subset of laryngeal neoplasms. We present the experience of a single institution to define clinical presentations and outcomes. MATERIALS AND METHODS: The pathology archives and clinical records of our center with the diagnosis of laryngeal tumors between the 2005 and 2018 were reviewed. Age, gender, symptoms, location of the tumor, histopathological diagnosis, treatment modality and disease status were discussed. RESULTS: 657 patients were diagnosed with laryngeal tumor between 2005 and 2018 and 13 patients with non-epithelial tumors were identified. The majority of the patients were male. The age ranged between 13 and 93 years. The most common tumor localizations were vocal cords and subglottis. Seven patients were diagnosed with malignant tumors and six patients had benign tumors. Chondrosarcoma was the most common malignant mesenchymal tumor. Others were leiomyosarcoma, fibrosarcoma and liposarcoma. The most common benign non-epithelial tumors were schwannoma and hemangioma. Plexiform neurofibroma and granular cell tumor were the other benign tumors. Eleven patients underwent excisional biopsy. One patient underwent partial laryngectomy and one had total laryngectomy. Three cases presented with recurrent tumor. Among the recurrent cases, two were malignant tumors. CONCLUSION: Non-epithelial tumors of the larynx are rare and have a wide histological diversity. Immunohistochemical studies are of great importance in the diagnosis of these tumors. Primary mesenchymal tumors of the larynx should be kept in mind in differential diagnosis.

Comparison of the effectiveness of Brandt-Daroff Vestibular training and Epley Canalith repositioning maneuver in benign Paroxysmal positional vertigo long term result: A randomized prospective clinical trial.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is the most common peripheral cause of vertigo. It can be defined as transient vertigo induced by rapid change in head position, associated with a characteristic paroxysmal positional nystagmus. Posterior canal benign paroxysmal positional vertigo is the most frequent form of BPPV. The aim of our study was to investigate and compare the effectiveness of Epley maneuver and Brand-Daroff home exercises for the treatment of posterior canal BPPV. METHODS: A total of 50 patients between 27 and 76 years of age who were diagnosed with unilateral posterior canal into BPPV were randomized prospectively into two groups. In Group-1, modified particle repositioning maneuver and in Group-2 Brandt-Daroff exercises were utilized as treatment. Patients were followed weekly. Cure weeks were recorded. The patients were followed for 12 to 24 months for recurrence. RESULTS: The recovery rates at the first, second and third week controls were 76%, 96% and 100% for Group-1 (modified Epley maneuver) and 64%, 88% and 100% for Group-2 (Brandt-Daroff exercises) respectively. The recovery rates were similar for both groups. The average follow-up duration was 18 months. In Group 1, 7 patients (28%) and in Group 2, 5 patients (20%) had recurrence, which was also similar with no statistical difference. CONCLUSION: It was concluded that both Brandt-Daroff Exercises and Modified Epley maneuvers were almost equally effective in the treatment of BPPV.

Comparison of Clinical Results in Nasal Tip Augmentation Either Via Face to Face or Back to Back Technique With Autogenous Auricular Conchal Cartilage.

OBJECTIVE: To compare the objective and subjective findings between patients who underwent nasal tip augmentation surgery via two different methods using autogenous auricular conchal cartilage. MATERIALS AND METHODS: This study included the data of 21 patients who underwent nasal tip augmentation surgery. The patients were randomly divided in two groups according to the technique used to form a double layer columellar strut graft; either face to face (group 1) and back to back (group 2). All patients were assessed via nasal obstruction symptom evaluation scale (NOSE) and via acoustic rhinometry and rhinomanometry at preoperative and postoperative 1st and 6th months. RESULTS: There was statistically significant improvement in symptom score in both patient groups with no difference inbetween. Total nasal resistance decreased nonsignificantly at the end of 6th month in both groups; 13.1 Pa/cm3 to 8.6 Pa/cm3 and 10.3 Pa/cm3 to 9.5 Pa/cm3 respectively. There was no significant increment in MCA values for both groups except left MCA1. CONCLUSIONS: We achieved good results in tip augmentation via both techniques. An autogenous conchal cartilage is a good alternative to replace lacking caudal septal cartilage. It provides safe and stable support to the nasal tip. However, further comprehensive studies with larger sample size and long follow-up are required to elucidate any difference between these two techniques.

[The effects of CO2 laser posterior cordotomy on quality of life in patients with bilateral vocal cord paralysis]. / Iki tarafli vokal kord paralizili hastalarda CO2 lazer posteriyor kordotominin yasam kalitesine etkisi.

OBJECTIVES: In this study, we evaluated the effects of CO2 laser posterior transverse cordotomy on the quality of life in patients with bilateral vocal cord paralysis (BVCP). PATIENTS AND METHODS: Between April 2009 and October 2011, 14 patients with BVCP who underwent unilateral CO2 laser posterior cordotomy were included. The functional outcome of the procedure was assessed by the changes in the subscales of the Quality of Life Survey (SF-36). Postoperative glottic space and voice quality were evaluated using an arbitrary classification system. RESULTS: There was a statistically significant improvement in all parameters of SF-36 subscales after surgery, except the emotional role functioning and mental health component subscales. No significant correlation was found between the findings of the SF-36 subscales and stages of glottic space. No correlation was observed between the changes in the SF-36 subscales and voice quality. There was a significant correlation between the stages of glottic space and voice quality (p=0.036). CONCLUSION: The CO2 laser surgery is a safe and effective surgical modality which improves quality of life in the patients with BVCP. It can be also suggested that a considerable amount of tissue ablation is not necessarily required with this surgery and this helps to prevent impairment of voice quality.

Treatment Results and Postoperative Complications of Single-Stage Tracheal Resection in Adolescent Patients with Post-Intubation Tracheal Stenosis, Compared to Adults.

Objective: The purpose of this study was to analyze the treatment outcomes and postoperative complications of tracheal resection in patients under the age of 19 years with post-intubation tracheal stenosis, and to compare the results with those of adults. Methods: Data were retrospectively retrieved from the medical records, including demographic characteristics, perioperative features, any postoperative complications and follow-up statuses of the patients. Treatment results and postoperative complications were compared between adolescent and adult groups. Results: Overall, anastomotic and non-anastomotic complication rates in the adolescent group and the adult group were 40%, 40%, 10% and 63%, 44.4%, 33.3%, respectively. Overall treatment success rates based on tracheostomy tube and tracheal stent free status were 90% and 92.6% in adolescent and adults, respectively. Conclusion: Treatment success rates and incidence of anastomotic complications were found similar in patients under the age of 19 years and adult patients who underwent single-stage tracheal resection and end to end anastomosis for treatment of post-intubation tracheal stenosis.

The reliability of SleepStrip as a screening test in obstructive sleep apnea syndrome.

OBJECTIVES: This study aims to assess the reliability of SleepStrip as a screening test in obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: Seventy-two patients (50 males, 22 females; mean age 51.4±11.1 years; range 20 to 74 years) with OSAS were included in this prospective, non-randomized double-blinded single cohort study between May 2008 and February 2009. Patients who underwent an attended overnight polysomnography (PSG) and consented to participate in the study were asked to use SleepStrip device within the week following PSG recording. The apnea-hypopnea index (AHI) was compared with the SleepStrip score (Sscore). RESULTS: The mean body mass index of patients was 31.1±4.3. Both AHI and Sscore were obtained in 64 patients. There was a strong correlation between Sscore and AHI (r=0.76, p<0.001). The sensitivity and specificity of the SleepStrip were 94.4% and 93.5% when used to diagnose cases with AHI = or >40. The sensitivity and specificity of the SleepStrip was reduced to 80% and 87.2% when AHI threshold was chosen as = or >25 and 83.3% and 76.5% for AHI = or >15 respectively. CONCLUSION: There is a strong correlation between SleepStrip and AHI. SleepStrip was found to be effective in diagnosing severe OSAS with AHI = or >40, however, its diagnostic capability was reduced in patients with lower AHI's who constitute the main target of screening.

The role of selective neck dissection in pathological N1 squamous cell carcinomas of the head and neck.

OBJECTIVES: This study aims to evaluate the effectiveness of selective neck dissection (SND) in stage pN1 head and neck cancers. PATIENTS AND METHODS: Patients who underwent neck dissection due to squamous cell carcinoma of oral cavity, larynx, oro-hypopharynx were evaluated retrospectively. Sixty-one patients diagnosed with pathological N1 by neck dissection were included in the study. Thirty-four of the 61 necks, to which SND was applied, comprised the study group, and 27 necks, which underwent comprehensive neck dissection (CND), comprised the control group. RESULTS: Neck recurrence rates were 4.9% for all cases, 5.9% for the SND group and 3.7% for the CND group. Two- and five-year disease-specific survival rates were similar for SND group (78.6%, 72.5%) and CND group (90.5%, 82.9%). Two- and five-year overall survival rates were also similar for SND group (67.6%, 58%) and CND group (81.5%, 66%). None of them were significantly different between groups (p>0.05). CONCLUSION: Selective neck dissection provides comparable results to CND in the treatment of pN1 necks.

The prognostic value of thyroid gland invasion in locally advanced laryngeal cancers.

BACKGROUND: Locally advanced laryngeal cancers can spread to the thyroid gland by direct invasion of cricothyroid membrane. The prevalence of thyroid gland invasion (TGI) and the predictive factors of TGI were well described in literature. However, the association of TGI with survival was undetermined yet. OBJECTIVES: The aim of this study is to analyze the effects of TGI on survival rates in patients with locally advanced laryngeal cancer. MATERIALS AND METHODS: Medical records of 91 patients who underwent total laryngectomy with thyroidectomy were retrospectively reviewed. Demographical, clinical, and histopathological characteristics of the patients were noted. Kaplan-Meier test was used for survival analysis. RESULTS: Histopathology reports revealed the prevalence of TGI as 14.3% (13/91). Survival analyses showed that TGI did not affect recurrence free (p = .078) and overall (p = .080) survival rates. CONCLUSIONS: Thyroid gland invasion is one of the characteristic features of locally aggressive laryngeal tumors. In this study, TGI is not a statistically significant prognostic factor that has impact on survival of the patients with locally advanced laryngeal cancer.

The rationale of using mesenchymal stem cells in patients with COVID-19-related acute respiratory distress syndrome: What to expect.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis with an extremely rapid progress resulting in thousands of patients who may develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) treatment. So far, no specific antiviral therapeutic agent has been demonstrated to be effective for COVID-19; therefore, the clinical management is largely supportive and depends on the patients' immune response leading to a cytokine storm followed by lung edema, dysfunction of air exchange, and ARDS, which could lead to multiorgan failure and death. Given that human mesenchymal stem cells (MSCs) from various tissue sources have revealed successful clinical outcomes in many immunocompromised disorders by inhibiting the overactivation of the immune system and promoting endogenous repair by improving the microenvironment, there is a growing demand for MSC infusions in patients with COVID-19-related ARDS in the ICU. In this review, we have documented the rationale and possible outcomes of compassionate use of MSCs, particularly in patients with SARS-CoV-2 infections, toward proving or disproving the efficacy of this approach in the near future. Many centers have registered and approved, and some already started, single-case or phase I/II trials primarily aiming to rescue their critical patients when no other therapeutic approach responds. On the other hand, it is also very important to mention that there is a good deal of concern about clinics offering unproven stem cell treatments for COVID-19. The reviewers and oversight bodies will be looking for a balanced but critical appraisal of current trials.

Management of pain after tonsillectomy: a prospective, randomized clinical study.

OBJECTIVES: We evaluated the alleviation of post-tonsillectomy pain with systemic and topical applications. PATIENTS AND METHODS: Data obtained from 78 patients (28 females, 50 males) who had undergone tonsillectomy for recurrent tonsillitis by conventional cold surgery were reviewed with prospective, randomized clinical study. Initially, the patients were assigned into topical and systemic drug groups. These groups were then divided into three sub-groups; (i) clindamycin, dexamethasone, and control (saline) (ii) groups for the topical drug group; (iii) cefprozil, amoxicillin+clavulanate and control (no medications except analgesic) for the systemic drug group. The intensity of pain perceived by the patients at 21 different times was assessed by visual analog scale and facial scale. RESULTS: No significant relation was found between topical or systemic antibiotic use and pain intensity after tonsillectomy. CONCLUSION: Neither topical application nor systemic administration is significantly superior to the other for postoperative management of pain.

Evaluation of amylase levels in the neck drainage and serum for early diagnosis of the pharyngocutaneous fistula.

OBJECTIVES: To assess the value of amylase levels in neck drainage and serum for the diagnosis of pharyngocutaneous fistula in the early postoperative period. PATIENTS AND METHODS: We conducted a prospective study in a tertiary referral setting. Thirty-two patients (31 males, 1 female; mean age 63; range 45 to 75 years) who had laryngectomy operation as the primary treatment were studied. Amylase levels in the neck drainage and serum were analyzed in the first three postoperative days. The results were compared between patients who developed pharyngocutaneous fistula and who did not. RESULTS: Serum amylase levels were significantly higher in pharyngocutaneous fistula group, whereas amylase in the neck drainage was not diagnostic. CONCLUSION: Serum amylase levels may be used in laryngectomy patients for the early diagnosis of pharyngocutaneous fistula.

Unexpected findings in the neck dissection specimens for primary head and neck squamous cell carcinoma.

OBJECTIVES: We aimed to determine the incidence of unexpected pathological findings observed during the histopathological examination of the neck dissection specimens performed for primary head and neck squamous cell carcinoma, and their impacts on the treatment and follow-up plans. PATIENTS AND METHODS: We retrospectively reviewed 410 patients (369 males, 41 females; 169 patients unilateral, 241 patients bilateral) with a diagnosis of squamous cell carcinoma of head and neck, who underwent 651 neck dissections. RESULTS: Unexpected pathological findings were found in 3.2% of patients and 2% of neck dissections. These unexpected findings were tuberculosis in eight patients (2%), metastatic papillary thyroid carcinoma in three patients (0.7%), Warthin,s tumor in one patient and cystic hygroma in one patient. All patients who had metastatic papillary thyroid carcinoma received radioactive iodine treatment after thyroidectomy. In control examinations, none of these cases had problem related to neither primary disease nor thyroid pathology. Only two of eight patients who had tuberculosis in lymph nodes received medical treatment for tuberculosis, while the others were observed by clinical and radiological examinations. None of these patients had problems related to tuberculosis. We had no long-term follow-up results for cystic hygroma and Warthin,s tumor since these patients did not continue their routine examinations. CONCLUSION: During the pathologic examination of neck dissections, unexpected pathologic findings may occasionally be encountered. Most frequently seen unexpected findings were tuberculosis lymphadenitis and metastatic papillary thyroid carcinoma. However, these pathologic findings do not seem to affect the management of the primary disease.

Prognosis of subglottic carcinoma: Is it really worse?

It is traditionally accepted that subglottic carcinoma has a worse prognosis than tumors arising in other subsites of the larynx, owing to its tendency to present in advanced stages, with a high incidence of cartilage invasion and extralaryngeal spread. The incidence of subglottic carcinoma varies among series, mainly because there is no uniform definition of the upper boundary of the subglottis. The extent of the tumor may be difficult to define because subglottic carcinoma may spread through the submucosa without visible mucosal changes. There is also a rich lymphatic network in the subglottis draining to the prelaryngeal and paratracheal lymph nodes, which are usually not involved by cancers arising in other laryngeal subsites. Current literature data indicates that early-stage subglottic carcinoma can be treated using radiotherapy or chemoradiotherapy with high locoregional control and survival rates. In advanced stage subglottic carcinoma, combination of surgery followed by radiotherapy or chemoradiotherapy resulted in comparable outcomes, as in advanced carcinomas from the rest of the larynx. Stage for stage, it is likely that the prognosis for subglottic carcinoma and of glottic and supraglottic cancers is similar.

Hypothyroidism after primary surgical treatment for laryngeal and hypopharyngeal cancer.

OBJECTIVES: We investigated the incidence of hypothyroidism after treatment of laryngeal or hypopharyngeal cancer (LHC), and evaluated its relationship with treatment modalities. PATIENTS AND METHODS: Thyroid functions of 42 patients (41 males, 1 female; mean age 58 years; range 35 to 81 years) undergoing surgical treatment with (74%) or without adjuvant radiotherapy for LHC were prospectively evaluated preoperatively, on the 15th day, and in the sixth month postoperatively. The results were compared in relation to the treatment methods employed. RESULTS: The overall incidence of post-treatment hypothyroidism was 23.8%. Five patients had hypothyroidism in the early postoperative period, and this number increased to 10 after six months. All patients with hypothyroidism had undergone total laryngectomy with bilateral neck dissection, followed by radiotherapy. A significantly higher incidence of hypothyroidism was associated with total laryngectomy, bilateral neck dissection, level VI dissection, partial or bilateral thyroidectomy, adjuvant radiotherapy, and upper mediastinal radiotherapy. CONCLUSION: The incidence of post-treatment hypothyroidism is not rare in LHC patients, requiring long-term monitoring of thyroid functions to prevent associated morbidities.

[The relationship between lymph node size and metastasis and extracapsular spread in squamous cell carcinoma of the larynx, orohypopharynx, and oral cavity]. / Larenks, orohipofarenks ve oral kavite yassi hücreli karsinomlarinda lenf nodu boyutu ile metastaz ve ekstrakapsüler yayilim arasindaki iliski.

OBJECTIVES: We examined the relationship between lymph node size and metastasis and extracapsular spread (ECS) in patients who underwent neck dissection for squamous cell carcinoma of the larynx, orohypopharynx, or oral cavity. PATIENTS AND METHODS: We retrospectively evaluated a total of 200 neck dissections performed in 128 patients (107 males, 21 females; mean age 56+/-11 years; range 26 to 81 years) with squamous cell carcinoma of the larynx, orohypopharynx, or oral cavity, and having complete clinical and pathologic data. Along with 442 metastatic lymph nodes (139 with ECS), the greatest axial diameter of the biggest benign lymph node obtained from each patient was measured. Lymph nodes were classified according to the neck zone and size, and the relationship of lymph node size with metastasis and ECS was examined. RESULTS: Lymph nodes with metastasis and ECS were often 11 to 30 mm in size and the highest rates of metastasis and ECS were seen in lymph nodes measuring 31 to 60 mm. However, approximately 40% and 25% of lymph nodes with metastasis and ECS, respectively, were in the range of 1 to 10 mm, which is not clinically accepted as pathologic. CONCLUSION: In larynx, orohypopharynx, and oral cavity squamous cell carcinomas, the clinical assessment of the size of neck lymph nodes is usually not a predictor for lymph node metastasis or ECS. Thus, until methods like sentinel lymph node biopsy become standard to determine occult metastasis, the importance of elective neck dissections is still valid in clinically N0 necks.

Selective neck dissection in surgically treated head and neck squamous cell carcinoma patients with a clinically positive neck: Systematic review.

Adequate treatment of lymph node metastases is essential for patients with head and neck squamous cell carcinoma (HNSCC). However, there is still no consensus on the optimal surgical treatment of the neck for patients with a clinically positive (cN+) neck. In this review, we analyzed current literature about the feasibility of selective neck dissection (SND) in surgically treated HNSCC patients with cN + neck using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. From the reviewed literature, it seems that SND is a valid option in patients with cN1 and selected cN2 neck disease (non-fixed nodes, absence of palpable metastases at level IV or V, or large volume ->3 cm-multiple lymph nodes at multiple levels). Adjuvant (chemo) radiotherapy is fundamental to achieve good control rates in pN2 cases. The use of SND instead a comprehensive neck dissection (CND) could result in reduced morbidity and better functional results. We conclude that SND could replace a CND without compromising oncologic efficacy in cN1 and cN2 cases with the above-mentioned characteristics.

P53 gene mutations in surgical margins and primary tumor tissues of patients with squamous cell carcinoma of the head and neck.

AIMS AND BACKGROUND: The frequency of p53 mutations in primary tumors, the effect of the mutations on some clinical and pathological features of head and neck squamous cell carcinoma, and the impact of p53 mutations in the surgical margins on local recurrence were determined, MATERIAL AND METHODS: We investigated the presence of p53 mutations in primary tumor samples and in the surgical margins of 34 patients with head and neck cancer using single strand conformational polymorphism and sequencing analysis. RESULTS: The p53 mutations (codons 175addAT, 175delGC, 206G --> A, and 248delC) were found in the primary tumor samples of 15 of 34 patients (44.12%) and in the surgical margins of 5 of the 15 tumors (33.33%) with p53 mutations. CONCLUSIONS: We found no statistically significant association between the presence of p53 mutations in the primary tumor, the clinical and pathological features, or outcome of head and neck squamous cell carcinoma in this study. Furthermore, the presence of p53 mutations in the surgical margins may not increase the risk of local-regional recurrence, but probably increases the risk of developing distant metastases or second primary tumors.