Case report: Ultrasound diagnosis of fish bone penetration into the thyroid.

Ultrasonography is useful in the diagnosis of foreign body migrations (eg, fish bones) into the soft tissues of the neck.

Validity and reliability of the reflux symptom score.

OBJECTIVES/HYPOTHESIS: To develop and validate the Reflux Symptom Score (RSS), a self-administered patient-reported outcome questionnaire for patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Prospective controlled study. METHODS: A total of 113 patients with LPR were enrolled and treated with diet and 3 months of pantoprazole, alginate, and/or magaldrate depending on the LPR characteristics (acid, nonacid, or mixed). Eighty asymptomatic individuals completed the study. Patients and controls completed the RSS twice within a 7-day period to assess test-retest reliability. Internal consistency was measured using Cronbach's α for the RSS items in patients and controls. Validity was assessed by comparing the baseline RSS with the Reflux Symptom Index (RSI) and Voice Handicap Index (VHI). Seventy-seven patients completed the RSS at baseline and after 6 and 12 weeks of treatment to assess responsiveness to change. The RSS cutoff for determining the presence and absence of LPR was examined by receiver operating characteristic analysis. RESULTS: Test-retest reliability (rs = 0.921) and internal consistency reliability (α = 0.969) were high. RSS exhibited high external validity indicated by a significant correlation with the RSI (rs = 0.831). Internal validity was excellent based on the higher RSS in patients compared with controls (P = .001). RSS, RSI, and VHI scores significantly improved from pre- to posttreatment, indicating a high responsiveness to change. RSS >13 can be considered suggestive of LPR-related symptoms. RSS was not influenced by the occurrence of gastroesophageal reflux disease, LPR subtypes, or patient characteristics. CONCLUSIONS: RSS is a self-administered patient-reported outcome questionnaire that demonstrates high reliability and excellent criterion-based validity. RSS can be used in diagnosing and monitoring LPR disease. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:E98-E107, 2020.

MALDI Orbitrap mass spectrometry for fast and simplified analysis of novel street and designer drugs.

BACKGROUND: New strategies of rapid high-throughput analysis of street drugs without time-consuming sample preparations are necessary due to the massive variety of illicit substances available on the market. METHODS: We used matrix-assisted laser desorption/ionization (MALDI) high-resolution mass spectrometry (HRMS) to identify substances in 74 drug samples obtained from anonymous drug users who participate in the drug prevention initiative "checkit!". We compared our methodology with results derived from "checkit!" where samples are analyzed by high performance liquid chromatography (HPLC) coupled to ultraviolet diode array detection (UV-DAD) as well as single Quad-MS. Reference substances were serially diluted for calibration curves to assess the possibility of obtaining quantitative information with MALDI using an ionic liquid matrix. RESULTS: All drug substances found by "checkit!" analysis were also identified by MALDI HRMS full scan without previous chromatographic separations, including the detection of additionally 16 substances not detected by "checkit!". Reference substances such as cocaine, lysergic acid diethylamide, levamisole and papaverine were detectable using the ionic liquid matrix N,N-diisopropylethylammonium α-cyanohydroxycinnamate. Serial dilutions revealed correlation coefficients ranging from 0.95 to 0.99. CONCLUSION: Considering the growing complexity in the analysis of designer drugs the presented method can be used either in parallel or instead of already established drug identification techniques as a fast and comprehensive primary screening tool.

Matrix-assisted laser desorption/ionization for simultaneous quantitation of (acyl-)carnitines and organic acids in dried blood spots.

RATIONALE: Screening for inborn errors of metabolism using mass spectrometry is part of nationwide newborn screening programs and involves the detection of disease relevant (acyl-)carnitines and organic acids from dried blood spots. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) is a well-established tool for proteomics approaches. In recent years, this technique has become more and more integrated in analysis and identification of small metabolites and disease biomarkers in daily clinical laboratories. METHODS: We used a combination of both MALDI and high-resolution accurate mass (HR/AM) mass spectrometry using a linear ion trap-Orbitrap for the identification of small molecules from dried blood spots that serve as biomarkers for inborn errors of metabolism. The levels of detected metabolite species were compared between healthy newborns and affected patients with various inborn errors of metabolism using isotopically labeled internal standards and new bioinformatics software, respectively. RESULTS: (Acyl-)carnitine levels from normal and affected patients could be quantified and differentiated. Additionally, using the high resolving power of full scan Orbitrap mass spectrometry and novel software tools we demonstrated the identification and quantification of disease-specific organic acids. CONCLUSIONS: MALDI-HR/AM and full scan spectra to obtain information for the metabolic status of patients is a promising complementary approach to electrospray ionization mass spectrometry by simplified sample preparation, facilitating the screening of hundreds of metabolites from small sample volumes.

Short-incubation mass spectrometry assay for lysosomal storage disorders in newborn and high-risk population screening.

The interest in early detection strategies for lysosomal storage disorders (LSDs) in newborns and high-risk population has increased in the last years due to the availability of novel treatment strategies coupled with the development of diagnostic techniques. We report the development of a short-incubation mass spectrometry-based protocol that allows the detection of Gaucher, Niemann-Pick A/B, Pompe, Fabry and mucopolysaccharidosis type I disease within 4h including sample preparation from dried blood spots. Optimized sample handling without the need of time-consuming offline preparations, such as liquid-liquid and solid-phase extraction, allows the simultaneous quantification of five lysosomal enzyme activities using a cassette of substrates and deuterated internal standards. Applying incubation times of 3h revealed in intra-day CV% values ranging from 4% to 11% for all five enzyme activities, respectively. In a first clinical evaluation, we tested 825 unaffected newborns and 16 patients with LSDs using a multiplexed, turbulent flow chromatography-ultra high performance liquid chromatography-tandem mass spectrometer assay. All affected patients were identified accurately and could be differentiated from non-affected newborns. In comparison to previously published two-day assays, which included an overnight incubation, this protocol enabled the detection of lysosomal enzyme activities from sample to first result within half a day.