Negative and positive predictive values of nerve monitoring in thyroidectomy

Background Recurrent nerve injury is 1 of the most important complications of thyroidectomy. During the last decade, nerve monitoring has gained increasing acceptance in several centers as a method to predict and to document nerve function at the end of the operation. We evaluated the efficacy of a nerve monitoring system in a series of patients who underwent thyroidectomy and critically analyzed the negative predictive value (NPV) and positive predictive value (PPV) of the method. Methods. NIM System efficacy was prospectively analyzed in 447 patients who underwent thyroidectomy between 2001 and 2008 (366 female/81 male; 420 white/47 nonwhite; 11 to 82 years of age; median, 43 years old). There were 421 total thyroidectomies and 26 partial thyroidectomies, leading to 868 nerves at risk. The gold standard to evaluate inferior laryngeal nerve function was early postoperative videolaryngoscopy, which was repeated after 4 to 6 months in all patients with abnormal endoscopic findings. Results. At the early evaluation, 858 nerves (98.8%) presented normal videolaryngoscopic features after surgery. Ten paretic/paralyzed nerves (1.2%) were detected (2 unexpected unilateral paresis, 2 unexpected bilateral paresis, 1 unexpected unilateral paralysis, 1 unexpected bilateral paralyses, and 1 expected unilateral paralysis). At the late videolaryngoscopy, only 2 permanent nerve paralyses were noted (0.2%), with an ultimate result of 99.8% functioning nerves. Nerve monitoring showed absent or markedly reduced electrical activity at the end of the operations in 25/868 nerves (2.9%), including all 10 endoscopically compromised nerves, with 15 false-positive results. There were no false-negative results. Therefore, the PPV was 40.0%, and the NPV was 100%. Conclusions. In the present series, nerve monitoring had a very high PPV but a low NPV for the detection of recurrent nerve injury. (C) 2011 Wiley Periodicals, Inc. Head Neck 34: 175-179, 2012

Laryngeal malformation in Richieri-Costa Pereira syndrome: New findings

Laryngeal structural anomalies were described in 13 cases of Richieri-Costa Pereira syndrome, and four previously reported cases were reviewed. The 17 individuals examined had the typical laryngeal anomalies and vocal disorders previously described. The new findings are the laryngeal microweb observed in three cases and arytenoid anteriorization movement observed in 14 cases. (C) 2012 Wiley Periodicals, Inc.

Individually Customized Implants for Laryngoplasty-Are They Possible?

Objective. To standardize the design of individually fitted implants based on computed tomographic (CT) images for use in medialization laryngoplasty without intraoperative voice monitoring. Study Design. Prospective tomographic and anatomical experimental study of 10 human cadaveric larynges. Methods. CT scans of 10 excised human larynges were analyzed to define the shape and size of ideal implants for medialization laryngoplasty. Silicone implants were designed according to CT parameters and used in simulated laryngoplasties in the laryngeal specimens. The efficacy of each implant in providing adequate medialization of the vocal fold was evaluated. Results. Diverse shapes and sizes of implants were obtained, reflecting variations in laryngeal anatomy. The implants enabled regular medialization of the entire extent of the free border of the vocal fold, including its posterior aspect. Medialization was considered adequate in all cases. Conclusions. This method proved to be a simple and efficient way to design individualized implants for medialization laryngoplasty, regardless of the size and shape of the larynx.

Expression of calcium binding protein S100 A7 (psoriasin) in laryngeal carcinoma

Many studies have reported increased expression of S100 A7 (psoriasin) in neoplastic lesions. Among them are studies on breast carcinoma, bladder squamous cell carcinoma, skin tumors and oral cavity squamous cell carcinoma. The expression of S100 A7 has not been described for laryngeal cancer. Objective: This study aims to identify the expression of the calcium-binding protein S100 A7 and its correlation with squamous cell carcinomas of the larynx. Material and Methods: Specimens from 63 patients were submitted to immunohistochemistry testing with antibody S100 A7. Results were classified and compared. Results: The group with highly differentiated tumors had the highest treatment failure scores. Moderately differentiated tumors had higher treatment failure scores than poorly differentiated tumors. Higher scores were predominantly seen on stages I and II in moderately differentiated tumors, whereas score distribution was more homogeneous in advanced stage disease (III and IV). Regarding failure in treatment, the group scoring zero (3/4 complications: 75%) differed significantly from the remaining groups (13/59: 22%). Conclusions: S100 A7 marker was expressed in 93.7% of laryngeal cancer cases, with higher positive correlation rates in more differentiated tumors and significantly lower rates of treatment failure. Scores had no impact on survival rates.

Neutrophil Paralysis in Plasmodium vivax Malaria

Background: The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects. Here, we examined the activation and function of neutrophils during acute episodes of malaria. Materials and Methods: Blood samples were collected from P. vivax-infected patients at admission (day 0) and 30-45 days after treatment with chloroquine and primaquine. Expression of activation markers and cytokine levels produced by highly purified monocytes and neutrophils were measured by the Cytometric Bead Assay. Phagocytic activity, superoxide production, chemotaxis and the presence of G protein-coupled receptor (GRK2) were also evaluated in neutrophils from malaria patients. Principal Findings: Both monocytes and neutrophils from P. vivax-infected patients were highly activated. While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production. Interestingly, neutrophils from the malaria patients expressed high levels of GRK2, low levels of CXCR2, and displayed impaired chemotaxis towards IL-8 (CXCL8). Conclusion: Activated neutrophils from malaria patients are a poor source of pro-inflammatory cytokines and display reduced chemotactic activity, suggesting a possible mechanism for an enhanced susceptibility to secondary bacterial infection during malaria.

Possible implication of Mdm2 as a prognostic marker in invasive laryngeal carcinoma

Laryngeal squamous cell carcinoma is one of the most common malignant neoplasms of the head and neck. In Brazil, laryngeal tumors represent 2% of all cancers and are associated with approximately 3,000 deaths annually. Human papillomavirus (HPV) has been reported to play an important role in the etiology of laryngeal cancer. The aim of the present study was to evaluate the expression of p53, p27, and Mdm2 in laryngeal carcinomas. Sixty-three larynx biopsies were selected for the study, including 9 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastasis and 27 laryngeal carcinomas with metastasis. Twenty-seven cervical lymph nodes from patients with metastatic lesions were also evaluated. The expression levels of p53, p27, and Mdm2 were assessed by immunohistochemistry using a computer-assisted system. HPV detection and typing were performed using PCR, and the HPV types that were evaluated included HPV 6, 11, 16, 18, 31 and 33. Out of 63 patients, 53 (84.1%) were positive for beta-globin (internal control), and 10 (15.9%) were beta-globin negative and therefore excluded from the evaluation. Thus, 7 (13.2%) out of 53 patients were HPV positive, and 46 (86.8%) out of 53 patients were HPV negative. Statistically significant differences (p < 0.05) in Mdm2 expression levels were observed in the in situ laryngeal carcinoma samples compared with the laryngeal carcinoma samples with metastasis. No statistically significant differences (p > 0.05) in either p53 or p27 expression levels were detected. These findings suggest that Mdm2 may be associated with the invasiveness and aggressiveness of laryngeal carcinomas.

Laryngeal involvement in pemphigus vulgaris: a proposed classification

Objective: (1) To investigate the incidence of laryngeal involvement in a large series of patients with pemphigus vulgaris, using endoscopic examination, (2) to describe the lesions, and (3) to establish a classification of laryngeal involvement in pemphigus vulgaris based on the location of the lesions. Study design: Prospective study. Methods: A total of 40 sequentially treated pemphigus vulgaris patients, diagnosed using clinical, histological and immunofluorescence criteria, were evaluated for laryngeal manifestations using endoscopic examination. The results were used to establish a graded classification of laryngeal involvement according to the location of the lesions. Results: Active laryngeal lesions (ulcers or blisters) were found in 16 patients (40 per cent). Of these, 37.5 per cent were classified as grade I, 20 per cent as grade II, 20 per cent as grade III and 17.5 per cent as grade IV. Conclusion: Laryngeal involvement is common in pemphigus vulgaris and must be considered at the point of diagnosis. Grade I lesions are the most frequent.

Experimental infection of suckling mice by subcutaneous inoculation with Oropouche virus

Oropouche virus, of the family Bunyaviridae, genus Orthobunyavirus, serogroup Simbu, is an important causative agent of arboviral febrile illness in Brazil. An estimated 500,000 cases of Oropouche fever have occurred in Brazil in the last 30 years, with recorded cases also in Panama, Peru, Suriname and Trinidad. We have developed an experimental model of Oropouche virus infection in neonatal BALB/c mouse by subcutaneous inoculation. The vast majority of infected animals developed disease on the 5th day post infection, characterized mainly by lethargy and paralysis, progressing to death within 10 days. Viral replication was documented in brain cells by in situ hybridization, immunohistochemistry and virus titration. Multi-step immunohistochemistry indicated neurons as the main target cells of OROV infection. Histopathology revealed glial reaction and astrocyte activation in the brain and spinal cord, with neuronal apoptosis. Spleen hyperplasia and mild meningitis were also found, without viable virus detected in liver and spleen. This is the first report of an experimental mouse model of OROV infection, with severe involvement of the central nervous system, and should become useful in pathogenesis studies, as well as in preclinical testing of therapeutic interventions for this emerging pathogen. (c) 2012 Elsevier B.V. All rights reserved.

Interferon-gamma and interleukin-10 production by mononuclear cells from patients with advanced head and neck cancer

OBJECTIVE: This study aims to evaluate the production of interferon-gamma and interleukin-10 by stimulated peripheral blood mononuclear cells isolated from patients with supraglottic laryngeal cancer before and after surgical treatment. METHODS: Fourteen patients with advanced supraglottic laryngeal cancer were studied. Cultures of peripheral blood mononuclear cells isolated during the preoperative and late postoperative periods were stimulated with concanavalin A and Bacille Calmette-Guerin, and the supernatant concentrations of interferon-gamma and interleukin-10 were measured. RESULTS: For non-stimulated cultures, the interferon-gamma levels produced by the preoperative period and the late postoperative period cultures were lower than the levels produced by the control group cultures. The interferon-gamma levels after stimulation with concanavalin A were higher in the late postoperative period cultures than in the preoperative evaluation cultures. Stimulation with Bacille Calmette-Guerin led to the production of similar levels of interferon-gamma and interleukin-10 by all cultures; thus, stimulation increased the levels of interferon-gamma produced by both the preoperative and postoperative cultures relative to the levels produced by the corresponding unstimulated cultures. CONCLUSION: Patients with advanced supraglottic laryngeal cancer exhibit an in vitro deficiency in interferongamma secretion by mononuclear cells. Stimulated cells seem to recover this function during the postoperative period.

Prognostic value of thumb pain sensation in birth brachial plexopathy

Objective: To evaluate the prognostic value of absent thumb pain sensation in newborns and young infants with birth brachial plexopathy. Methods: We evaluated 131 patients with birth brachial plexopathy with less than two months of age. Pain sensation was evoked by thumb nail bed compression to evaluate sensory fibers of the upper trunk (C6). The patients were followed-up monthly. Patients with less than antigravity elbow flexion at six months of age were considered to have a poor outcome. Results: Thirty patients had absent thumb pain sensation, from which 26 showed a poor outcome. Sensitivity of the test was 65% and specificity was 96%. Conclusion: Evaluation of thumb pain sensation should be included in the clinical assessment of infants with birth brachial plexopathy.

IL-12p40 Deficiency Leads to Uncontrolled Trypanosoma cruzi Dissemination in the Spinal Cord Resulting in Neuronal Death and Motor Dysfunction

Chagas' disease is a protozoosis caused by Trypanosoma cruzi that frequently shows severe chronic clinical complications of the heart or digestive system. Neurological disorders due to T. cruzi infection are also described in children and immunosuppressed hosts. We have previously reported that IL-12p40 knockout (KO) mice infected with the T. cruzi strain Sylvio X10/4 develop spinal cord neurodegenerative disease. Here, we further characterized neuropathology, parasite burden and inflammatory component associated to the fatal neurological disorder occurring in this mouse model. Forelimb paralysis in infected IL-12p40KO mice was associated with 60% (p<0.05) decrease in spinal cord neuronal density, glutamate accumulation (153%, p<0.05) and strong demyelization in lesion areas, mostly in those showing heavy protein nitrosylation, all denoting a neurotoxic degenerative profile. Quantification of T. cruzi 18S rRNA showed that parasite burden was controlled in the spinal cord of WT mice, decreasing from the fifth week after infection, but progressive parasite dissemination was observed in IL-12p40KO cords concurrent with significant accumulation of the astrocytic marker GFAP (317.0%, p<0.01) and 8-fold increase in macrophages/microglia (p<0.01), 36.3% (p<0.01) of which were infected. Similarly, mRNA levels for CD3, TNF-alpha, IFN-gamma, iNOS, IL-10 and arginase I declined in WT spinal cords about the fourth or fifth week after infection, but kept increasing in IL-12p40KO mice. Interestingly, compared to WT tissue, lower mRNA levels for IFN-gamma were observed in the IL-12p40KO spinal cords up to the fourth week of infection. Together the data suggest that impairments of parasite clearance mechanisms in IL-12p40KO mice elicit prolonged spinal cord inflammation that in turn leads to irreversible neurodegenerative lesions.

Endoscopic Laser Thyroarytenoid Myoneurectomy in Patients with Adductor Spasmodic Dysphonia: A Pilot Study on Long-Term Outcome on Voice Quality

Objectives. Adductor spasmodic dysphonia (ADSD) is a focal laryngeal dystonia, which compromises greatly the quality of life of the patients involved. It is a severe vocal disorder characterized by spasms of laryngeal muscles during speech, producing phonatory breaks, forced, strained and strangled voice. Its symptoms result from involuntary and intermittent contractions of thyroarytenoid muscle during speech, which causes vocal fold to strain, pressing each vocal fold against the other and increasing glottic resistance. Botulinum toxin injection remains the gold-standard treatment. However, as injections should be repeated periodically leading to voice quality instability, a more definitive procedure would be desirable. In this pilot study we report the long-term vocal quality results of endoscopic laser thyroarytenoid myoneurectomy. Study Design. Prospective study. Methods. Surgery was performed in 15 patients (11 females and four males), aged between 29 and 73 years, diagnosed with ADSD. Voice Handicap Index (VHI) was obtained before and after surgery (median 31 months postoperatively). Results. A significant improvement in VHI was observed after surgery, as compared with baseline values (P = 0.001). The median and interquartile range for preoperative VHI was 99 and 13, respectively and 24 and 42, for postoperative VHI. Subjective improvement of voice as assessed by the patients showed median improvement of 80%. Conclusions. Because long-term follow-up showed significant improvement of voice quality, this innovative surgical technique seems a satisfactory alternative treatment of ADSD patients who seek a definite improvement of their condition.

Nebulized 0.5, 2.5 and 5 ml L-epinephrine for post-extubation stridor in children: a prospective, randomized, double-blind clinical trial

Nebulized l-epinephrine has been recommended for the treatment of viral croup. However, the few studies assessing its effect on post-extubation stridor (PES) have shown conflicting results. We compared the efficacy and safety of nebulized l-epinephrine at three different doses for the treatment of PES. We conducted a prospective, randomized, double-blind trial including all consecutive children with a PES score of a parts per thousand yen4 (Westley score). The primary efficacy outcome was change in PES score at 40 min. A reduction of a parts per thousand yen2 points in stridor score was defined as clinically significant. A total of 96 patients were randomly assigned to receive one of three doses of nebulized l-epinephrine upon achieving a PES score of 4 or more following extubation. Stridor score and vital signs were recorded before treatment, and at 20, 40, 60 and 180 min after nebulization. Baseline characteristics were similar among all study groups. No significant difference was detected among the treatments based on change in Westley score by intent-to-treat analysis. In addition, the difference in the number of patients who clinically improved among the treatment groups was not significant (p = 0.54). Patients receiving 5 ml nebulized epinephrine had a significant increase of systolic and diastolic blood pressure at 40 and 180 min. Nebulized l-epinephrine at doses of 0.5, 2.5 and 5 ml demonstrated a lack of dose response in effect on PES and a modestly clinically significant increase in undesired side effects (heart rate and blood pressure) at higher doses.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 casecontrol studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.590.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.420.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.540.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.160.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Videolaryngostroboscopy and voice evaluation in patients with rheumatoid arthritis

Arthritis may affect the larynx and produce symptoms such as hoarseness and vocal fatigue. Objective: This paper aimed to evaluate the laryngeal manifestations of rheumatoid arthritis. Methods: This is prospective study assessed 27 patients with rheumatoid arthritis with the aid of videolaryngostroboscopy, auditory-perceptual analysis of the speech using the GIRBAS scale, acoustic analysis and the Voice Handicap Index questionnaire. Results: Nineteen patients had laryngeal complaints, the main ones being intermittent dysphonia and sensation of a foreign body in the throat. The most frequent laryngoscopical finding was overlapping arytenoids. Three patients had low pitch, nine patients had mild dysphonia and roughness. Median acoustic measures were: F0, 198.39 Hz; Jitter, 0.815; Shimmer, 4.915; and NHR, 0.144. Regarding the Voice Handicap Index, the median score was zero in all domains. There was a statistically significant correlation between voice complaints and the domains of this index. Functional classes were significantly correlated to: overlapping arytenoids (p = 0.001), PPQ (p = 0.0257), Shimmer (p = 0.0295), APQ (p = 0.0195), and the VHI physical (p = 0.0227) and total domains (p = 0.0425). Conclusion: Laryngeal complaints were reported by 70.4% of the patients and laryngoscopical alterations were observed in 48% of the subjects. Voice acoustic evaluation and self-perception were altered.