Pharmacokinetics-Based Pediatric Dose Evaluation and Optimization Using Saliva - A Case Study.

Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling in children is challenging, alternative PK sampling strategies are needed. In this case study we evaluated the suitability of saliva as alternative PK matrix to simplify studies in infants, investigating metamizole, an analgesic used off-label in infants. Six plasma and 6 saliva PK sample collections were scheduled after a single intravenous dose of 10 mg/kg metamizole. Plasma/saliva pharmacometric (PMX) modeling of the active metabolites 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA) was performed. Various reduced plasma sampling scenarios were evaluated by PMX simulations. Saliva and plasma samples from 25 children were included (age range, 5-70 months; weight range, 8.7-24.8 kg). Distribution of metamizole metabolites between plasma and saliva was without delay. Estimated mean (individual range) saliva/plasma fractions of 4-MAA and 4-AA were 0.32 (0.05-0.57) and 0.57 (0.25-0.70), respectively. Residual variability of 4-MAA (4-AA) in saliva was 47% (28%) versus 17% (11%) in plasma. A simplified sampling scenario with up to 6 saliva samples combined with 1 plasma sample was associated with similar PK parameter estimates as the full plasma sampling scenario. This case study with metamizole shows increased PK variability in saliva compared to plasma, compromising its suitability as single matrix for PK studies in infants. Nonetheless, rich saliva sampling can reduce the number of plasma samples required for PK characterization, thereby facilitating the conduct of PK studies to optimize dosing in pediatric patients.

Eustachian Tube Balloon Dilation in Children: Short- and Long-Term Outcome.

OBJECTIVE: Eustachian Tube Balloon Dilation (ETBD) represents an innovative therapeutic approach for chronic Eustachian tube dysfunction (CETD), a common disease in children. Some evidence of a benefit of ETBD in the adults exist in contrast to sparse reports in children. The objective was to analyze short- and long-term outcome of ETBD in children with CETD. METHODS: A retrospective chart-review was performed in a cohort of 19 children (mean age 13 years, 7-17) who underwent ETBD. The following parameters were analyzed: tubomanometry (R-value), tympanogram, hearing (CPT-AMA, Air-bone gap [ABG]), Eustachian Tube Score (ETS and ETS-7), and Eustachian Tube Disease questionnaire (ETDQ). RESULTS: Twenty-four ears were dilated (in 5 patients subsequently after successful first intervention) and grouped as A (17) without and B (7) with additional T-tube insertion. Most children suffered from either chronic otitis media with effusion or chronic perforation (12, 63%), the remainder comprising recurrent otitis media, adhesive otitis media and CETD with barotrauma. Mean duration of symptoms were 7/8.2 years and mean follow-up 13.7/11.1 months. Eighty percent of patients reported a subjective benefit. Accordingly, the R-value, ETS, and ETS-7 were significantly (P < .05) improved. Tympanometry, CPT-AMA and ABG showed a positive trend, but the result was not significant. Tympanic retraction remained largely the same; a spontaneous closure of a chronic tympanic perforation was seen in 1 of 3 cases. CONCLUSIONS: The high subjective benefit and some significant objective improvement warrants further analysis of ETBD as part of the therapeutic management in pediatric CETD.

Acute bilateral blindness due to diffuse outer retinopathy following clear lens exchange: a case report.

BACKGROUND: As the trend of refractive lens exchange for presbyopia continues to grow, our case report shows the first occurrence of an acute bilateral outer retinopathy following uncomplicated sequential clear lens extraction in an otherwise healthy individual. CASE PRESENTATION: A 54-year-old male without significant medical history benefited from a sequential bilateral lens exchange for presbyopia. He then experienced a rapid vision loss in both eyes, accompanied by photopsias and myodesopsias, with symptoms appearing respectively 4 and 3 weeks after the surgeries. Multimodal imaging revealed a fulminant outer retinopathy, leading to a total loss of light perception within a few days. Immediate intravenous corticosteroid therapy was administered, permitting to recover a small area of central visual function in both eyes, enabling shape and color distinction. The primary diagnostic hypothesis is a presumed autoimmune retinopathy, triggered by the cataract extraction, while an alternative diagnosis could be a toxic reaction secondary to the use of intracameral cefuroxime and lidocaine during the surgery. CONCLUSION: In this report, the authors describe the first recorded instance of outer retinopathy following cataract surgery. This occurrence raises the possibility of auto-immunization leading to retinal atrophy and vision loss as a potential outcome after undergoing cataract surgery.

Prospective Validation of Tubomanometry in Children With Normal Eustachian Tube Function.

OBJECTIVES: Tubomanometry (TMM), described initially by Estève, is a relatively new manometric method for testing the eustachian tube function (ETF). This study presents the analysis of the measurement of ETF of healthy children by TMM, which has, to date, not been properly evaluated. The objectives of the study were to establish normative data for TMM and to demonstrate TMM as a reliable and valid method for measuring ETF in children. DESIGN: The evaluation, after initial power analysis, comprised 35 children from 6 to 15 years of age with an intact tympanic membrane, no severe ET dysfunction, and less than three inflammations of the middle ear in their medical history. TMM was performed twice at three pressure levels for both ears. Statistical assessment of the various parameters of TMM was performed with emphasis on the R value and possible age dependency. RESULTS: The 90th percentile for the R value was calculated to be 1.12. No clinically relevant age effect regarding the use of TMM as a screening method for children was found. Healthy children showed an opening within normal limits for the so-called R value in 88%; a delayed opening was measured in 6%, and rarely no opening was measured in 2%. CONCLUSIONS: TMM is a reliable tool for measuring ETF in children. The normal limit for the R value should be set at 1.12. The proposed measuring algorithm and results can be used to calculate sensitivity and specificity in a future study.

Silastic sheeting in staged ear surgery: Is there still a role for this procedure?

OBJECTIVE: To review long-term outcomes for chronic otitis media with and without cholesteatoma in staged canal-wall-up tympanoplasty with temporary silastic sheeting and to compare hearing and recurrence results with the literature. METHODS: Retrospective data analysis of all patients suffering from chronic otitis media with or without cholesteatoma (COMC/COM) and treated by staged canal-wall-up (CWU) technique with silastic insertion between 1992 and 2012. Literature analysis in PubMed 1990-2017. RESULTS: 74 cases were included in the analysis. In COMC (n = 47) a total of 2 (4%) recurrent and 14 (30%) residual cholesteatoma were documented. The postoperative hearing test showed a pure-tone-average (PTA) of 36 dB hearing level (HL) and an air-bone-gap (ABG) of 21 dB HL. A significant improvement was only observed for stage I disease (PTA 8 dB HL and ABG 9 dB HL). In COM (n = 27) postoperative PTA and ABG were significantly improved by 33 dB HL and 23 dB HL, respectively. Mean postoperative follow-up was 47 months (12-173) for COMC and 22 months (2-120) for COM. CONCLUSIONS: The cholesteatoma recurrence rate in this study reflects contemporary published rates. Assessment of hearing outcome is difficult due to the low number of cases and very high heterogeneity of published data. Still, the staged CWU procedure with temporary silastic sheeting seems to bear some advantages in regard to hearing. The role of additional factors such as Eustachian Tube function to assess outcome should be considered. An internationally agreed upon reporting system should be followed, if various surgical approaches are to be compared. LEVEL OF EVIDENCE: 3.

Co-therapy with S-adenosylmethionine and nicotinamide riboside improves t-cell survival and function in Arts Syndrome (PRPS1 deficiency).

Arts syndrome or phosphoribosyl-pyrophosphate-synthetase-1 (PRPS1) deficiency is caused by loss-of-function mutations in the PRPS1 gene (Xq22.3). PRPS1 is an initial and essential step for the synthesis of the nucleotides of purines, pyrimidines, and nicotinamide. Classically, affected males present with sensorineural hearing loss, optic atrophy, muscular hypotonia, developmental impairment, and recurrent severe respiratory infections early in life. Treatment of a 3-year old boy with S-adenosylmethionine (SAM) replenished erythrocyte purine nucleotides of adenosine and guanosine, while SAM and nicotinamide riboside co-therapy further improved his clinical phenotype as well as T-cell survival and function.

Monitoring the recovery time of children after tonsillectomy using commercial activity trackers.

An observational prospective feasibility study in which children received a tracker 2 weeks before a tonsillectomy and were required to wear it until four weeks postoperatively. The parents used a diary to log the estimated steps of their child. As primary endpoint, the compliance of complete datasets was compared between the tracker and the diary. As secondary endpoints, the agreement of steps between tracker and diary, and the recovery time after tonsillectomy were analyzed.Twenty-four patients (50% male) with a median age of 6 years were recruited. The tracker had a complete dataset compliance of 91.7% in the pre-operative and 58.3% in postoperative period, whereas the diary's compliance was 62.5% in the pre-operative and 12.5% in the postoperative period. The difference of 29.2% and 45.8% in the pre-operative and postoperative periods between the tracker and the diary was significant (p < 0.005). The tracker and diary had a mean agreement difference of 1063 steps per day. Mean recovery time was 21 days after tonsillectomy.Conclusion: The results of this pilot study support the use of a tracker in terms of compliance and practicability. Consumer-level activity trackers are a viable alternative to conventional manual logging for clinical use in pediatric research.Trial registration: ClinicalTrials.gov Identifier: NCT03174496 What is known: • Consumer-level activity trackers are already used in clinical research to monitor steps and physical activity. • The use of consumer-level activity trackers in clinical studies has mostly been validated in the adult population. What is new: • This study proves the feasibility of using physical activity trackers in a pediatric population before and after a surgical intervention. • Recovery of a patient could be assessed with an activity tracker.

Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome.

Down syndrome (DS) is characterized by the occurrence of three copies of human chromosome 21 (HSA21). HSA21 contains a cluster of four interferon receptor (IFN-R) genes: IFNAR1, IFNAR2, IFNGR2, and IL10RB. DS patients often develop mucocutaneous infections and autoimmune diseases, mimicking patients with heterozygous gain-of-function (GOF) STAT1 mutations, which enhance cellular responses to three types of interferon (IFN). A gene dosage effect at these four loci may contribute to the infectious and autoimmune manifestations observed in individuals with DS. We report high levels of IFN-αR1, IFN-αR2, and IFN-γR2 expression on the surface of monocytes and EBV-transformed-B (EBV-B) cells from studying 45 DS patients. Total and phosphorylated STAT1 (STAT1 and pSTAT1) levels were constitutively high in unstimulated and IFN-α- and IFN-γ-stimulated monocytes from DS patients but lower than those in patients with GOF STAT1 mutations. Following stimulation with IFN-α or -γ, but not with IL-6 or IL-21, pSTAT1 and IFN-γ activation factor (GAF) DNA-binding activities were significantly higher in the EBV-B cells of DS patients than in controls. These responses resemble the dysregulated responses observed in patients with STAT1 GOF mutations. Concentrations of plasma type I IFNs were high in 12% of the DS patients tested (1.8% in the healthy controls). Levels of type I IFNs, IFN-Rs, and STAT1 were similar in DS patients with and without recurrent skin infections. We performed a genome-wide transcriptomic analysis based on principal component analysis and interferon modules on circulating monocytes. We found that DS monocytes had levels of both IFN-α- and IFN-γ-inducible ISGs intermediate to those of monocytes from healthy controls and from patients with GOF STAT1 mutations. Unlike patients with GOF STAT1 mutations, patients with DS had normal circulating Th17 counts and a high proportion of terminally differentiated CD8+ T cells with low levels of STAT1 expression. We conclude a mild interferonopathy in Down syndrome leads to an incomplete penetrance at both cellular and clinical level, which is not correlate with recurrent skin bacterial or fungal infections. The constitutive upregulation of type I and type II IFN-R, at least in monocytes of DS patients, may contribute to the autoimmune diseases observed in these individuals.

[Hematochezia and right-sided upper abdominal pain after puncture of a liver abscess in a 75-year-old male]. / Hämatochezie und rechtsseitiger Oberbauchschmerz nach Punktion eines Leberabszesses bei einem 75-Jährigen.

This article presents the case of a 75-year-old male patient, who underwent a percutaneous abscess puncture of a liver abscess. A few days after the puncture and drainage there was a sudden onset of right upper quadrant abdominal pain accompanied by hematochezia. The patient presented with markedly elevated liver enzyme levels and a significant drop in hemoglobin concentration. After gastroscopy and abdominal computed tomography (CT) in the portal venous phase no bleeding source could be identified. A false aneurysm of the cystic artery was identified only after a CT angiography of the abdomen. Due to spontaneous cessation of the bleeding a cholecystectomy was subsequently performed for definitive treatment of the false aneurysm.

Appropriateness of antimicrobial prescribing in a Swiss tertiary care hospital: a repeated point prevalence survey.

AIMS OF THE STUDY: Inappropriate use of antimicrobials is associated with the emergence of antimicrobial resistance and adverse events. Antimicrobial stewardship programmes may both optimise treatment of infections and reduce antimicrobial resistance but are implemented in only a minority of Swiss hospitals. In addition, data on prescribing patterns and quality are scarce. We conducted a repeated point prevalence survey to evaluate the quality of antimicrobial prescribing in a single tertiary care centre. METHODS: Antimicrobial use was audited twice (summer 2017 and winter 2018) among all patients admitted to the University Hospital Basel, Switzerland. Data were collected from the electronic health record. Appropriateness of antimicrobial use was evaluated according to previously published rules and local national guidelines. RESULTS: We evaluated 1112 patients of whom 378 (34%) received 548 prescriptions in total (30% for prophylaxis). Penicillins with β-lactamase inhibitors were most commonly used (30%), followed by cotrimoxazole (12%) and ceftriaxone (7%). Intravenous administration was chosen in 56% of patients. Prior to antimicrobial therapy, blood cultures were collected in 69% of patients. Overall, 182 (33%) prescriptions were not appropriate; reasons included lack of indication (11%), incorrect dosing (7%), delay in intravenous to oral switch (9%) or non-adherence to local guidelines (15%). A minority of patients received antimicrobials despite documented allergies (2%). Almost 38% of empirical prescriptions were inappropriate, compared with only 19% of prophylactic and 20% of targeted prescriptions. Penicillins with β-lactamase inhibitors and cephalosporins were most commonly involved in inappropriate prescribing (>50%) followed by carbapenems (30%), narrow-spectrum penicillins (17%) and cotrimoxazole (6%), with oral administration being involved less frequently than intravenous administration (15 vs 37%). Infectious diseases consultation and presence of immunosuppression were associated with reduced odds (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.21–0.70 and OR 0.31, 95% CI 0.17–0.54, respectively) of inappropriate prescription in the per-patient multivariable analysis, whereas being admitted to a surgical or intensive care unit was associated with increased odds (OR 1.83 and 5.67) compared with a medical unit. CONCLUSION: Almost one third of prescriptions were inappropriate in our tertiary care centre despite local guidelines and an on-demand infectious diseases consultation service. Our results underscore the need for expanding current antimicrobial stewardship efforts, including national initiatives such as stewardship and prescribing guidelines, repeated surveys and identification of areas for improvement including timely intravenous to oral switches in order to reduce the consequences of inappropriate prescribing and of multidrug resistant organisms.

Dose evaluation of intravenous metamizole (dipyrone) in infants and children: a prospective population pharmacokinetic study.

PURPOSE: The prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants < 1 year. We aimed to assess the pharmacokinetics of the main metabolites of metamizole in children aged 3-72 months. METHODS: A single dose of 10 mg/kg metamizole was administered intravenously for postoperative analgesia. Pharmacokinetic samples were drawn at predefined time points. Pharmacokinetics of the main active metabolite 4-methylaminoantipyrine and three other metabolites was characterized by both non-compartmental and population pharmacokinetic analysis. AUC0-inf of 4-methylaminoantipyrine was calculated by non-compartmental analysis for two age cohorts (3-23 months, 2-6 years) and compared with the 80-125% range of adult dose-adjusted reference exposure (AUCref). Population pharmacokinetic analysis investigated age and weight dependency of the pharmacokinetics and optimal dosing strategies to achieve equivalent adult exposure. RESULTS: A total of 25 children aged 5 months-5.8 years (7.8-24.8 kg) with at least one concentration sample were included; 19 children had ≥ 5 predefined samples up to 10 h after metamizole dose administration. AUC0-inf of 4-methylaminoantipyrine in children 2-6 years was 29.9 mg/L/h (95% CI 23.4-38.2), significantly lower than AUCref (80-125% range 39.2-61.2 mg/L/h). AUC0-inf of 4-methylaminoantipyrine in infants < 2 years was 43.6 mg/L/h (95% CI 15.8-119.0), comparable with AUCref, while infants < 12 months showed increased exposure. Observed variability could be partially explained by covariates weight and age. CONCLUSIONS: Age-related changes in pharmacokinetics of 4-methylaminoantipyrine requires reduced weight-based IV dosing in infants < 1 year compared with infants and children up to 6 years (5 versus 10-20 mg/kg) to achieve equivalent adult exposure. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02660177 .

Sialoblastoma of the submandibular gland: a distinct entity?

Sialoblastoma is a rare congenital malignant tumor of the salivary glands. A case of a submandibular sialoblastoma in a 1.5-year-old child is presented. A comparative analysis on 79 pediatric cases reported in the literature suggests a less aggressive behavior for submandibular sialoblastoma in comparison with other sites. Classically, diagnosis is confirmed by open biopsy, but fine-needle aspiration may offer an alternative with reduced morbidity. Expression of AFP and high levels of Ki-67 have been associated with poor prognosis. Whilst early surgical resection with negative margins is widely accepted as first-line treatment, there is no consensus on therapy of recurrence and follow-up. MRI and sonography represent valid tools for the follow-up, which is usually restricted to 3-5 years.Conclusion: Submandibular sialoblastomas may have a different biological profile in comparison with parotid tumors with the absence of metastasis and much lower rate of recurrence. Comprehensive diagnostics should include additional options such as fine-needle aspiration and markers to assess cell proliferation and AFP. Literature suggests that surgery alone is sufficient for the treatment of tumors with low malignancy. Follow-up should be tailored according to the tumor site and might be limited to 3-5 years. What is Known: • Sialoblastoma is a rare congenital malignant tumor with an unpredictable clinical outcome. What is New: • Sialoblastoma of submandibular origin seems to have a less aggressive behavior in comparison with other sites. • Fine-needle aspiration and markers to assess proliferation index (i.e., suggestive of potential more aggressive course/malignancy) should be strongly considered in the diagnostic work-up. • Radical surgery as first-line therapy and a 3-5-year follow-up are acceptable for tumors with a low malignancy.

Prosthetic valve endocarditis caused by Pseudomonas aeruginosa with variable antibacterial resistance profiles: a diagnostic challenge.

BACKGROUND: Infective endocarditis (IE) caused by gram-negative bacilli is rare. However, the incidence of this severe infection is rising because of the increasing number of persons at risk, such as patients with immunosuppression or with cardiac implantable devices and prosthetic valves. The diagnosis of IE is often difficult, particularly when microorganisms such as Pseudomonas aeruginosa, which rarely cause this infection, are involved. One of the mainstays for the diagnosis of IE are persistently positive blood cultures with the same bacteria, while polymicrobial bacteremia usually points to another cause, e.g. an abscess. The antimicrobial resistance profile of some P. aeruginosa strains may change, falsely suggesting an infection with several strains, thus further increasing the diagnostic difficulties. CASE PRESENTATION: A 66-year old male patient who had a transcatheter aortic valve implantation (TAVI) one year previously developed fever seven days after an elective inguinal hernia repair. During the following four weeks, P. aeruginosa with different antibiotic resistance profiles was repeatedly isolated from blood cultures. Repeated trans-esophageal echocardiograms (TEE) were negative and an infection by different P. aeruginosa strains was suspected. Extensive diagnostic workup for an infectious focus was performed with no results. Finally, an oscillating mass on the aortic valve was detected by TEE five weeks after the initial positive blood cultures. P. aeruginosa endocarditis was confirmed by culture of the surgically removed valve. Whole genome sequencing of the last two P. aeruginosa isolates (valve and blood culture) revealed identical strains, with genome mutations for AmpR, AmpD and OprD. CONCLUSIONS: The diagnosis of prosthetic valve endocarditis is particularly difficult for several reasons. The modified Duke criteria have a lower sensitivity for patients with prosthetic valve endocarditis and the infection may be caused by "unusual" pathogens such as P. aeruginosa. Patients with repeatedly positive blood cultures should make clinicians suspicious for endocarditis even if imaging studies are negative and if isolated pathogens are "unusual". Repeatedly positive blood cultures for P. aeruginosa should be considered as "persistent bacteremia" (suspicious for IE) even in the presence of different antibiotic susceptibility patterns, since P. aeruginosa might rapidly activate or deactivate resistance mechanisms depending on antibiotic exposition.

Influence of a resin-based blood culture medium on the time to clearance of methicillin-susceptible Staphylococcus aureus bloodstream infection - A retrospective cohort study.

We evaluated the improved sensitivity and time to detection of new resin-based blood culture (BC) media in Staphylococcus aureus bloodstream infection. We observed a significantly longer duration of bacteremia and shorter time to detection compared to traditional charcoal-based BC media, which may influence diagnostic work-up and treatment duration.

Sodium Polystyrene Sulfonate and Cytomegalovirus-Associated Hemorrhagic Duodenitis: More than Meets the Eye.

BACKGROUND Hemorrhagic duodenitis is an exceptionally rare adverse event of sodium polystyrene sulfonate (SPS) treatment and is a common manifestation of cytomegalovirus (CMV) reactivation. SPS is known to cause marked inflammation in the lower gastrointestinal tract, including colonic necrosis, whereas involvement of the small bowel is uncommon. Although its effectiveness and safety has been disputed since its introduction, SPS remains widely used due to lack of alternatives. CMV infection and reactivation are well-known complications after solid-organ transplantation, particularly in seronegative recipients receiving organs from seropositive donors, and is associated with significant morbidity and mortality. The lower gastrointestinal tract is more commonly involved, but infections of all parts of the intestine are observed. CASE REPORT Here, we report the case of a 56-year-old man who presented with severe upper-gastrointestinal bleeding. Hemorrhagic duodenitis was initially attributed to the use of SPS, as abundant SPS crystals were detected in the duodenal mucosa but we found only 2 CMV-infected endothelial cells. Two weeks later, gastrointestinal bleeding recurred. However, this time, abundant CMV-infected cells were demonstrated in the duodenal biopsies. CONCLUSIONS Our case report highlights an uncommon adverse event after SPS use with a simultaneous CMV reactivation. The main difficulty was to differentiate between CMV reactivation and CMV as an "innocent bystander". This demonstrates the challenge of decision-making in patients with complex underlying diseases.

The Application of Next-Generation Sequencing for Mutation Detection in Autosomal-Dominant Hereditary Hearing Impairment.

OBJECTIVE: Identification of the causative mutation using next-generation sequencing in autosomal-dominant hereditary hearing impairment, as mutation analysis in hereditary hearing impairment by classic genetic methods, is hindered by the high heterogeneity of the disease. PATIENTS: Two Swiss families with autosomal-dominant hereditary hearing impairment. INTERVENTION: Amplified DNA libraries for next-generation sequencing were constructed from extracted genomic DNA, derived from peripheral blood, and enriched by a custom-made sequence capture library. Validated, pooled libraries were sequenced on an Illumina MiSeq instrument, 300 cycles and paired-end sequencing. Technical data analysis was performed with SeqMonk, variant analysis with GeneTalk or VariantStudio. The detection of mutations in genes related to hearing loss by next-generation sequencing was subsequently confirmed using specific polymerase-chain-reaction and Sanger sequencing. MAIN OUTCOME MEASURE: Mutation detection in hearing-loss-related genes. RESULTS: The first family harbored the mutation c.5383+5delGTGA in the TECTA-gene. In the second family, a novel mutation c.2614-2625delCATGGCGCCGTG in the WFS1-gene and a second mutation TCOF1-c.1028G>A were identified. CONCLUSION: Next-generation sequencing successfully identified the causative mutation in families with autosomal-dominant hereditary hearing impairment. The results helped to clarify the pathogenic role of a known mutation and led to the detection of a novel one. NGS represents a feasible approach with great potential future in the diagnostics of hereditary hearing impairment, even in smaller labs.

Bilateral congenital deafness: What investigations should be performed?

BACKGROUND: The introduction of newborn hearing screening has led to earlier identification of children with congenital sensorineural hearing loss (SNHL). Aetiological clarification offers several benefits. There is currently a lack of agreement on which examinations should be recommended. OBJECTIVE: Descriptive review of the literature reporting investigations performed to establish the aetiology of congenital SNHL and comparison of the management policy in Swiss referral centres. METHODS: PubMed Search from 1985 to March 2016 with specific search terms; study selection according to inclusion/exclusion criteria; narrative analysis by use of defined criteria and question-naire. RESULTS: Ninety-two studies were finally included in this review. Forty studies investigated more than a single aetiology. Overall frequencies of aetiological parameters investigated were: genetic (47 studies), radiological (35), ophthalmic (35), serological (32), cardiac (25), renal (14), endocrine (12), neurological (8). Most of the studies were retrospective and various limitations such as poor population description, incomplete data or deficiencies in methodological quality were frequently detected. The variability detected in the investigative approach chosen by Swiss referral centres reflects the heterogeneous data seen in the literature. CONCLUSIONS: The evidence in the literature regarding an appro-priate evaluation is mostly of low quality and difficult to assess owing to high heterogeneity. Nevertheless, imaging, genetic testing, neuropaediatric and ophthalmological evaluations, electrocardiograms and cytomegalovirus analysis have been identified as examinations to be included in the assessment of children with congenital SNHL. There is a need for international consensus on the various issues of such an evaluation, such as choice of investigations and diagnostic criteria.

Diagnostic value of core needle biopsy and fine-needle aspiration in salivary gland lesions.

BACKGROUND: Core needle biopsy (CNB) has gained acceptance as a minimally invasive procedure in the head and neck. Nevertheless, many concerns arise regarding the value and safety of this method in the assessment of salivary gland lesions. METHODS: This prospective study comprises 111 patients with a salivary gland lesion. The results of ultrasound-guided CNB were compared with those of fine-needle aspiration (FNA) in the 103 histologically verified cases. RESULTS: CNB achieved a higher accuracy than FNA in identifying true neoplasms (98% vs 91%) and detecting malignancy (99% vs 87%), and was also superior to FNA providing a specific diagnosis (93% vs 74%). In both methods, no complications, such as bleeding, infection, nerve injury, or tumor-cell seeding, occurred. CONCLUSION: CNB is a simple, safe, and highly accurate procedure, which should be considered as an additional diagnostic tool in the assessment of salivary gland lesions. © 2015 Wiley Periodicals, Inc. Head Neck 38: E346-E352, 2016.

Value of narrow band imaging in the early diagnosis of laryngeal cancer.

BACKGROUND: Narrow band imaging (NBI) is a new imaging technique for the depiction of tumor-specific neoangiogenesis. The purpose of the present study was to assess the value of NBI in the early diagnosis of laryngeal cancer. METHODS: This prospective study includes 205 consecutive patients with a laryngeal lesion scheduled for microlaryngoscopy. NBI was immediately performed after white light endoscopy (WLE), whereas excisional biopsy was carried out for histologic verification of diagnosis. RESULTS: In identifying laryngeal cancer and its precursor lesions, NBI with WLE showed a significantly higher sensitivity (97% vs 79%) and accuracy (97% vs 90%) than WLE alone, but the specificity (96% vs 95%) was essentially equal in both methods. CONCLUSION: NBI qualifies for rapid detection and delineation of suspicious lesions. Additionally, this noninvasive method is also beneficial in a variety of benign lesions.