Staphylococcus aureus nasal colonization level and intracellular reservoir: a prospective cohort study.

Staphylococcus aureus is a major pathogen in humans. The nasal vestibule is considered as the main reservoir of S. aureus. However, even though the nasal cavity may also be colonized by S. aureus, the relationships between the two sites are still unclear. We conducted a prospective study in humans to assess the S. aureus colonization profiles in the vestibule and nasal cavity, and to investigate the presence of intracellular S. aureus in the two sites. Patients undergoing ear, nose, and throat surgery were swabbed during endoscopy to determine S. aureus nasal load, genotype, and presence of intracellular S. aureus. Among per-operative samples from 90 patients, the prevalence of S. aureus carriage was 32.2% and 33.3% in the vestibule and the nasal cavity, respectively. The mean S. aureus load was 4.10 and 4.25 log10 CFU/swab for the nasal vestibule and nasal cavity, respectively (P > 0.05). Genotyping of S. aureus revealed that all nasal strains isolated from a given individual belong to the same clonal complex and spa-type. An intracellular carriage was observed in 5.6% of the patients, all of whom exhibited a S. aureus vestibule load higher than 3 log10 CFU/swab. An intracellular niche was observed in the vestibule as well as in the nasal cavity. In conclusion, the nasal cavity was also found to be a major site of S. aureus carriage in humans and should draw attention when studying host-pathogen interactions related to the risk of infection associated with colonization.

Technique of flat-mount immunostaining for mapping the olfactory epithelium and counting the olfactory sensory neurons.

The pathophysiology underlying olfactory dysfunction is still poorly understood, and more efficient biomolecular tools are necessary to explore this aspect. Immunohistochemistry (IHC) on cross sections is one of the major tools to study the olfactory epithelium (OE), but does not allow reliable counting of olfactory sensory neurons (OSNs) or cartography of the OE. In this study, we want to present an easy immunostaining technique to compensate for these defects of IHC. Using the rat model, we first validated and pre-screened the key OSN markers by IHC on cross sections of the OE. Tuj-1, OMP, DCX, PGP9.5, and N-cadherin were selected for immunostaining on flat-mounted OE because of their staining of OSN dendrites. A simple technique for immunostaining on flat-mounted septal OE was developed: fixation of the isolated septum mucosa in 0.5% paraformaldehyde (PFA) preceded by pretreatment of the rat head in 1% PFA for 1 hour. This technique allowed us to correctly reveal the olfactory areas using all the 5 selected markers on septum mucosa. By combining the mature OSN marker (OMP) and an immature OSN marker (Tuj-1), we quantified the mature (OMP+, Tuj-1-), immature (OMP-, Tuj-1+), transitory (OMP+, Tuj-1+) and total OSN density on septal OE. They were respectively 42080 ± 11820, 49384 ± 7134, 14448 ± 5865 and 105912 ± 13899 cells per mm2 (mean ± SD). Finally, the same immunostaining technique described above was performed with Tuj-1 for OE cartography on ethmoid turbinates without flat-mount.

Benign Paroxysmal Vertigo of Childhood. Video Recordings of Episodes.

OBJECTIVES: The main objective was to describe the nystagmus observed during benign paroxysmal vertigo (BPV) of childhood, which is one of the criteria included in the three versions of the International Classification of Headache Disorders that has never been specified. The secondary objectives were to emphasize the usefulness of a mobile phone to record nystagmus and discuss the physiopathology of this nystagmus. PATIENT: A 6-year-old boy complained of approximately 30 to 50 vertigo attacks, most of them lasting around 1 minute, during a 6-month period. INTERVENTION: Otoneurologic history and examination, audiovestibular exploration, and brain imaging were performed between the attacks. Video recording by the parents' mobile phone and video electroencephalography recording during a 1-day hospitalization were performed during the episodes. MAIN OUTCOME MEASURE: Analysis of seven video recordings performed by the parents and four during a 1-day hospitalization, as well as follow-up. RESULTS: The assessment between the attacks confirmed the diagnosis of BPV according to International Classification of Headache Disorders criteria. Video recordings constantly demonstrated a strong left horizontal nystagmus present at fixation in all direction of gaze, enhanced in left gaze. This nystagmus was associated with a rightward body deviation. CONCLUSION: The clinical presentation was more consistent with a peripheral vestibular deficit than with a central disorder. We encourage video recording of their child by the parents because it will help both to define the ictal nystagmus and to understand the underlying pathophysiology. The latter is discussed and is probably more complex than initially thought in BPV.

Exercise laryngoscopy in athletes and sportsmen: an easy way to assess exercise-induced laryngeal obstruction.

BACKGROUND: Exercise-induced laryngeal obstruction (EILO) is an exercise-dependent dyspnoea, linked to a laryngeal closure during physical effort. It may concern from 5% to 7% of adolescents and young athletic adults. EILO is a quite recently described condition: standardized diagnostic criteria and consensual management are still to come. Formal diagnosis of EILO requires a continuous laryngoscopy during exercise (CLE). This test allows visualization of laryngeal abnormalities during an effort but is only accessible in specialized centres. AIMS: We wanted to assess performance of a simplified CLE (sCLE) procedure for EILO diagnosis in everyday practice. MATERIAL AND METHODS: The procedure consisted in a continuous flexible videolaryngoscopy during a cycloergometre cardio-pulmonary exercise test. Screening questionnaire and visual scoring of laryngeal abnormalities were performed. Patients clinically suspected of EILO were included from 2018 to 2020. RESULTS: Seventeen consecutive subjects had an indication for sCLE. Fifteen patients underwent sCLE, and EILO-linked significative abnormalities were observed in 80% of them, thus confirming the diagnosis. CONCLUSIONS: CLE can be done successfully in a simple way. Due to its simplicity, tolerance and contribution in EILO diagnosis, this simplified version of CLE may promote its widespread use in ENT and pulmonology practices, as an affordable confirmation test.

Dual laryngeal reinnervation in bilateral vocal fold paralysis: anatomical pitfalls.

BACKGROUND: Bilateral laryngeal reinnervation can be a promising procedure for reanimation of laryngeal muscles, but currently not yet standardized. Besides patient conditions some intraoperative anatomical pitfalls need to be solved. METHODS: Twelve human head and neck specimens (24 sides) have been studied using microdissection and histological serial sections of the nerves. The surgical anatomy of the dual reinnervation procedure according to JP Marie was investigated notably the branching pattern of the phrenic nerve (PN), the Ansa cervicalis (AC) and the recurrent laryngeal nerve (RLN). RESULTS: Despite variations of the AC, a prominent inferior common trunk for sterno-hyoid and sterno-thyroid muscles can be used in more than 90% of the specimens. If the AC is missing because of previous surgery, the tiny nerve of the thyro-hyoid muscle can be used preferred. The PN display a double roots pattern from C3 to C4 cervical plexus in 50% of the specimens. A single root pattern can be found and an end-to-lateral neurorraphy can be used. Intra-laryngeal nerves pattern of the RLN display tiny collaterals which cannot be selected for abduction-adduction activity. Direct implantation of the Y-shape great auricular nerve within the posterior crico-arytenoid muscles can be a reliable method leading to challenging mechanical and functional conditions. CONCLUSION: Several anatomical pitfalls, including intra-operative choices and variants of the donor nerves, but also the challenging intra-laryngeal dissection of the inferior laryngeal nerve need to be solved. A successful laryngeal reinnervation still needs further studies for a simplified procedure.

High endothelial venules are present in pharyngeal and laryngeal carcinomas and they are associated with better prognosis.

BACKGROUND: Tumors lymphocytic infiltration has prognostic and predictive value. However, the mechanisms involved in lymphocyte recruitment remain poorly characterized. High endothelial venules (HEV) are blood vessels specialized in lymphocyte recruitment, recently showing prognostic significance in some types of cancer. Their implications in laryngeal or pharyngeal cancer is largely unknown. AIM OF THE STUDY: To investigate the possible presence of HEVs in head and neck cancer. MATERIAL AND METHODS: Oropharyngeal (n = 61), hypopharyngeal (n = 53) and laryngeal (n = 21) squamous cell carcinomas were immunohistochemically studied with the MECA-79 antibody, which specifically recognizes HEVs. Histological and clinical factors were correlated with HEVs' presence. RESULTS: HEVs were present in 34% of tumors, showing significant correlations with oropharyngeal localization, higher lymphocytic response, lower tumor budding, lower T status, absence of distant metastases and better overall and progression-free survival. CONCLUSION: HEVs represent an important prognostic factor in head and neck cancer.

The Impact of Iron Supplementation for Treating Anemia in Patients with Chronic Kidney Disease: Results from Pairwise and Network Meta-Analyses of Randomized Controlled Trials.

After relative erythropoietin deficiency, iron deficiency is the second most important contributing factor for anemia in chronic kidney disease (CKD) patients. Iron supplementation is a crucial part of the treatment of anemia in CKD patients, and intravenous (IV) iron supplementation is considered to be superior to per os (PO) iron supplementation. The differences between the available formulations are poorly characterized. This report presents results from pairwise and network meta-analyses carried out after a comprehensive search in sources of published and unpublished studies, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations (International prospective register of systematic reviews PROSPERO reference ID: CRD42020148155). Meta-analytic calculations were performed for the outcome of non-response to iron supplementation (i.e., hemoglobin (Hgb) increase of <0.5-1.0 g/dL, or initiation/intensification of erythropoiesis-stimulating agent (ESA) therapy, or increase/change of iron supplement, or requirements of blood transfusion). A total of 34 randomized controlled trials (RCT) were identified, providing numerical data for analyses covering 93.7% (n = 10.097) of the total study population. At the network level, iron supplementation seems to have a more protective effect against the outcome of non-response before the start of dialysis than once dialysis is initiated, and some preparations seem to be more potent (e.g., ferumoxytol, ferric carboxymaltose), compared to the rest of iron supplements assessed (surface under the cumulative ranking area (SUCRA) > 0.8). This study provides parameters for adequately following-up patients requiring iron supplementation, by presenting the most performing preparations, and, indirectly, by making it possible to identify good responders among all patients treated with these medicines.

Correlation Between Semiquantitative Metabolic Parameters After PET/CT and Histologic Prognostic Factors in Laryngeal and Pharyngeal Carcinoma.

Positron emission tomography/computed tomography (PET/CT) has shown prognostic significance in head and neck cancer patients. The underlying pathologic features that could explain the mechanisms associated with this observation are not clear. To analyze the correlation between 18-F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake assessed by PET/CT in head and neck cancer and histopathologic prognostic factors. Ninety-nine patients with laryngeal and pharyngeal squamous cell carcinoma were retrospectively reviewed for pretreatment PET/CT measurements, namely standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The corresponding histologic material was evaluated for tumor stroma-related prognostic factors such as the amount and type of stroma, lymphocytic response, tumor budding activity, and size of tumor cell nests in the tumor core area and tumor front. TLG and MTV were associated with tumor localization, as they were higher in oropharyngeal tumors. These values were also associated with tumor cell nest size in the tumor core with higher values corresponding to tumors with smaller nests. MTV40% was marginally associated with fibroblastic stroma type and higher budding activity. SUVmax was not associated with the histological factors in the whole sample, but higher values trended with higher tumor budding activity and stroma-rich tumors of the oropharynx. 18F-FDG PET measurements in head and neck squamous cell carcinomas are associated with prognostic histopathologic factors and suggest a possible correlation of glucose metabolism to epithelial-to-mesenchymal transition.

Gene Expression Comparison Between the Primary Tumor and its Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma: A Pilot Study.

BACKGROUND/AIM: In metastatic head and neck squamous cell carcinoma (HNSCC) the metastatic tumor does not always keep the same gene expression profile as the parental tumor, which may influence the course of the disease. The aim of this study was to compare the expression of genes implicated in HNSCC carcinogenesis between the primary tumor and the corresponding lymph node metastasis. MATERIALS AND METHODS: Eighteen HNSCC, their corresponding node metastases and non-neoplastic tissues were studied by RT-qPCR for the expression of EGFR, VEGF, claudin7, maspin, survivin and SCCA. The levels of expression were correlated with histological characteristics and patients' prognosis. RESULTS: All genes except for survivin displayed different expression in node metastasis compared to the primary tumor. The expression of EGFR, survivin, maspin, and claudin7 in node metastasis and SSCA in the primary tumor affected the prognosis. SCCA expression is associated with the expression of claudin7 and maspin. P16-positive tumors expressed low levels of VEGF and SCCA, while keratinizing tumors over-expressed VEGF. CONCLUSION: Differential gene expression levels in node metastases compared to the primary tumor is linked to the prognosis of HNSCC patients. The histological/immunohisto-chemical characteristics of the tumor are associated with these genes expression changes.

Prognostic significance of tumor budding, tumor-stroma ratio, cell nests size, and stroma type in laryngeal and pharyngeal squamous cell carcinomas.

BACKGROUND: Despite immune microenvironment of head and neck squamous cell carcinoma (HNSCC) has been studied, there are no sufficient data on the role of tumor stroma factors. The aim of the study was to explore the prognostic and predictive role of these factors in a large series of HNSCC. METHODS: This is a retrospective study of 266 patients with laryngeal and pharyngeal SCC. Clinical data were correlated with the following histological parameters: tumor-stroma ratio (TSR), tumor budding activity (BA), cell nests size (CNS), and stroma type. RESULTS: Stroma-rich tumors, tumor budding, smaller CNS at core and front area, and fibroblastic stroma type, were all adverse prognostic factors (P < 0.0001, 0.001, 0.003, 0.001, 0.007, respectively). Stroma-poor tumors and with larger CNS showed good response to induction chemotherapy (P = 0.009 and 0.02, respectively). CONCLUSIONS: TSR, tumor budding, CNS, and stroma type are important prognostic and predictive factors in laryngeal and pharyngeal SCC.

Clinical characteristics and prognostic factors of sinonasal undifferentiated carcinoma: a multicenter study.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a very rare entity with a poor prognosis. Due to the lack of studies on the subject, evidence is lacking concerning its management. METHODS: A multicenter collaborative study was conducted to assess treatment strategy, oncological outcome, and prognostic factors. RESULTS: Definitive analyses focused on 54 patients with a majority of advanced stage; the 3-year overall survival (OS) and 3-year recurrence-free survival (RFS) rates were, respectively, 62.4% and 47.8%. During the follow-up, 18 patients (33.3%) died, 10 (18.5%) developed metastases, 7 had lymph-node involvement (13%), and 12 (22.2%) showed recurrence or local progression. In univariate analyses, treatment modalities associated with improved RFS were induction chemotherapy (p = 0.02) and intensity-modulated radiotherapy (p = 0.007). In the multivariate analyses, only induction chemotherapy (p = 0.047, hazard ratio [HR] = 0.39) was significantly associated with improved RFS. CONCLUSION: Multimodal therapies including induction chemotherapy and intensity-modulated radiotherapy may improve the prognosis of SNUC; surgery might improve local control. Further multicenter studies are required.

Intraoperative monitoring of the recurrent laryngeal nerve by vagal nerve stimulation in thyroid surgery.

The aim of the present study was to evaluate the thyroarytenoid muscle response during bilateral thyroid surgery using vagal nerve stimulation. 195 patients (390 nerves at risk) underwent a total thyroidectomy. The recurrent laryngeal nerve's function was checked by analyzing the amplitude and the latency of the thyroarytenoid muscle's responses after a vagal nerve's stimulation (0.5 and 1 mA) using the NIM3 Medtronic system. All patients were submitted to preoperative and postoperative laryngoscopy. 20 patients get no thyroarytenoid muscle response to the vagal nerve stimulation, and 14 postoperative recurrent laryngeal nerve palsies were confirmed (3.8 %). Two palsies were present after 6 months (0.51 %). All the patients with muscle's response have normal mobility vocal fold. The test sensitivity was 100 % and the test specificity was 98 %. Physiologically, the mean latencies of the muscular potentials for the right RLN were, respectively, 3.89 and 3.83 ms (p > 0.05) for the stimulation at 0.5 and 1 mA. The mean latencies for the left RLN were, respectively, 6.25 and 6.22 ms for the stimulation at 0.5 and 1 mA (p > 0.05). The difference of the latencies between the right and the left nerve was 2.30 ms (1.75-3.25 ms) with a stimulation of 0.5 or 1 mA (p < 0.05). Thyroarytenoid muscle's response via a vagal nerve stimulation showed a functional asymmetry of the laryngeal adduction with a faster right response. Surgically, this method can predict accurately an immediate postoperative vocal folds function in patients undergoing a bilateral thyroid surgery.

Clinical and Histologic Predictive Factors of Response to Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: Induction chemotherapy (IC) is occasionally used in head and neck cancer, leading to less extensive surgery and reduced need for irradiation. Factors predicting the response to IC have not been determined. In this study, we investigated the clinical and histopathologic factors that predict the response to IC. METHODS: Head and neck squamous cell carcinomas from 81 patients were analyzed; clinical factors, histologic parameters, and expression of p16 and p53 were correlated with response to chemotherapy and prognosis. RESULTS: Factors predicting a good response to IC were the nonoropharyngeal localization, a rich lymphocytic tissue response, and a low platelet-to-lymphocyte blood ratio before treatment. Response to IC did not correlate with prognosis, whereas a low neutrophil-to-lymphocyte ratio (NLR), the absence of a desmoplastic reaction, a rich lymphocytic tissue response, and the overexpression of p53 were associated with better prognosis. CONCLUSIONS: Lymphocytic tissue response, NLR, and nonoropharyngeal localization are factors predictive of response to IC.

Preauricular transmandibular and transzygomatic approach for tumors of the infratemporal fossa revisited.

AIM: To demonstrate the surgical technique and results in patients operated on with a preauricular transmandibular transzygomatic approach. METHODS: This surgical technique was used in 21 patients with benign and malignant tumors of the infratemporal fossa (ITF), operated on between 1999 and 2011. RESULTS: Twenty-one patients were enrolled in the study. There were 6 patients with benign tumors and 15 with malignant ones. No patients with benign lesions show any disease recurrence 5 years after surgery and present excellent functional and cosmetic results. Postoperatively, a reduction of pain was noted in all patients with malignant lesions. Four patients in this group, who are alive 5 years after surgery, do not demonstrate any disease progression. CONCLUSION: The described approach provides an excellent exposure of the ITF and could be the procedure of choice in the management of ITF tumors.

Human papillomavirus and head and neck squamous cell carcinomas in the South-East of France: prevalence, viral expression, and prognostic implications.

CONCLUSION: Human papillomavirus (HPV) infection, especially by HPV 16, is frequently detected in oropharyngeal squamous cell carcinoma (OSCC). The expression of viral oncoproteins in tumoral tissues of OSCCs suggests the implication of HPV in tumorogenesis. It should now be systematically detected and considered in each patient's treatment and outcome. OBJECTIVES: To investigate the prevalence of HPV infection, the oncogenic role of HPV in patients from the South-East of France with head and neck squamous cell carcinoma (HNSCC), and the resulting clinical implications. METHODS: Biopsy samples from 200 patients with HNSCC were analyzed. For each patient, one or two biopsies of tumoral tissue were analyzed simultaneously with a biopsy of healthy tissue. Fresh frozen tissues were tested by molecular techniques for HPV DNA detection and genotyping as well as mRNA expression of oncoproteins E6 and E7. Expression of p16 was also analyzed by immunohistochemical staining. RESULTS: HPV DNA tested positive in 11.5% of biopsy samples. The HPV prevalence was higher in OSCCs (91.3 vs 27.3, p < 0.0001) and in patients not consuming tobacco (65.2% vs 95.4%, p < 0.0001). The estimated 3-year overall survival rates were 67.0% for HPV-infected patients versus 39.9% for non-infected patients. The high-risk HPV 16 was the most common type detected (65.2%). In 12 of 18 patients exhibiting DNA of high-risk HPV in their tumor tissue, the same viral genome was also present in normal tissue. E6 and E7 expression was found in 9 of 14 tumoral biopsies tested for these markers.

Endoscopic parathyroidectomy in primary hyperparathyroidism.

During the past decade, endoscopic video-assisted parathyroidectomy (EP) for primary hyper parathyroidism (PHPT) has gained wider acceptance. The endoscopic gasless procedure described by P. Miccoli (1997-1998) offers an attractive technique. A routine preoperative localization study was performed with both ultrasonography and 99m TC-Sestamibi scintigraphy for each patient with sporadic PHPT. The criteria to select patients eligible for EP included absence of significant nodular goiter, a previous neck surgery, a need for concomitant thyroidectomy, a significant obesity, and multiple enlarged parathyroid glands. The surgical outcome and the use of preoperative localization together with the operative strategy were evaluated. From 2005 to 2009, 59 out of 75 patients (78%) were potentially candidates for this approach. An enlarged parathyroid gland was located by both types of imaging for 34 patients (57%) and by 99 m Tc-Sestamibi scintigraphy for 46 patients (77%). Conversion was required in 11 cases (18%). Nine patients had a negative preoperative imaging study and five underwent a successful EP. The operating time ranged from 35 to 120 min (median 45 min). Usually patients were discharged home at 48 h. There were no cases of permanent hypocalcemia or recurrent laryngeal nerve palsy. Postoperative review showed that all calcium and parathyroid hormone levels remained normal at 3 months except for 1 patient with a double adenoma. EP is a quick, safe, and effective procedure in a selected group of patients. Our results show that this technique can be easily introduced into a general head and neck practice.