Incidence of spontaneous hearing threshold shifts during modern concert performances.

OBJECTIVES: Concerts have long periods of intense sound with short break intervals. Hearing concerns are well known to performers; concertgoers largely ignore them. Preperformance and postperformance audiograms were compared to assess hearing threshold shifts with and without earplugs. METHODS: A prospective, randomized study in which 29 volunteers attended 3 concerts, encompassing 3 music genres. Audiograms, seating location, sound intensity, and earplug-use data were collected. Data were analyzed to determine frequency test-retest variability. RESULTS: Sound levels averaged 99.8 dBA, and the maximum was 125.6 dBA. Sixty-four percent (9/14) of participants without earplugs showed significant threshold shifts compared with 27% (4/15) of those using earplugs. No significant differences existed between music genres or seating location. CONCLUSIONS: This study showed a high incidence of threshold shifts in unprotected concertgoers. Sound levels exceeded all Occupational Safety and Health Act rules despite standardized sound systems. A significant reduction in threshold shifts was seen with the use of earplugs. EBM rating: A-1b.     

Intraductal shock-wave lithotripsy in complicated common bile duct stones

Summary Intracorporeal shockwave lithotripsy was performed in 36 patients with problematic common bile duct stones. All of the patients had undergone unsuccessful mechanical lithotripsy prior to this procedure. In 29 patients (80.6%), the stones were fragmented under cholangioscopic control and subsequently extracted with a Dormia basket. In seven patients, the procedure failed due to stone impaction or failure to intubate the common bile duct with a nasobiliary tube. No complications were observed. Cholangioscopically guided intracorporeal shockwave lithotripsy is a highly effective and safe procedure for the conservative treatment of complicated common bile duct stones.Abbreviations ESWL extracorporeal shock-wave lithotripsy - ISWL intracorporeal shock-wave lithotripsy Dedicated to Prof. Dr. med. Ludwig Demling on the occasion of his 70th birthday     

Legal factors associated with change in alcohol use and partner violence among offenders

Intimate partner violence (IPV) is a pervasive social concern that may be exacerbated by high rates of alcohol dependence among perpetrators. Society has attempted to combat IPV through various legal interventions, but the effects of specific legal factors on behavioral change and treatment compliance remain largely unexamined. The primary focus of the current study was to comprehensively evaluate the impact of various legal factors (i.e., judicial mandate, judicial monitoring, stage of change, and stake in conformity) on mandatory treatment compliance and behavioral change over a 12 week post-adjudication period among a high-risk sample of alcohol dependent IPV offenders (N = 60). Growth curve analyses revealed effects of judicial monitoring and stage of change such that participants reporting low perceived judicial monitoring and early stages of change reported higher initial levels and a more rapid reduction in IPV than those reporting high perceived judicial monitoring and late stages of change, who reported consistently low IPV. Although we found that legal factors were poor predictors of treatment compliance and alcohol use during treatment, the association between alcohol and IPV was moderated by the legal factors. Stake in conformity was negatively associated with IPV among low alcohol users and positively associated among high alcohol users whereas stage of change was negatively associated with IPV among high alcohol users. The current results suggest that pretreatment legal factors may represent an important consideration in reducing IPV among alcohol dependent offenders. Further research is required to determine the efficacy of legal factors in isolation of treatment as well as methods of manipulating these factors to optimally compliment a prescribed course of treatment.     

Coagulopathy after snake bite byBothrops neuwiedi: Case report and results of in vitro experiments

Summary Coagulation studies were performed in a patient who had been bitten by a snake of the speciesBothrops neuwiedi. The patient presented with hemorrhagic necrosis at the envenomization site and considerable bleeding from venous puncture sites. He developed a severe defibrination syndrome with a clottable fibrinogen level of approximately 0.1 g/l. Fibrinogen was not measurable by clotting time assay. Fibrin degradation products were greatly elevated. Treatment with antivenom caused an anaphylactic reaction within ten minutes and serum sickness after three days. In vitro experiments revealed thatB. neuwiedi venom directly activates Factors II and X, but does not activate Factor XIII. In vivo consumption of Factor XIII afterB. neuwiedi envenomization is ascribed to the action of Factor IIa. At low venom concentrations clotting is initiated by activation of prothrombin by the venom either directly or via Factor X activation. Treatment with heparin might be beneficial in coagulopathy secondary to snake bite by reducing circulating active thrombin. The venom contains thrombinlike proteases which cause slow clotting of fibrinogen, and plasmin-like components causing further proteolysis of fibrinogen and fibrin. Antivenom has no effect on the proteolytic action of the snake venom. The in vivo effects of antivenom are presumably caused by acceleration of the elimination of venom components from the circulation. Intravenous administration of antivenom caused normalization of blood coagulation parameters within 48 h.     

Discordance in Tumor Mutation Burden from Blood and Tissue Affects Association with Response to Immune Checkpoint Inhibition in Real-World Settings

BackgroundTumor mutation burden (TMB), a biomarker for immune checkpoint inhibitor (CPI) response, is reported by both blood- and tissue-based next-generation sequencing (NGS) vendors. However, the agreement between TMB from blood (bTMB) and tissue (tTMB) in real-world settings, both in absolute value and association with CPI response, is not known.Materials and MethodsThis study utilizes Sarah Cannon’s precision medicine platform, Genospace, to harmonize clinico-genomic data from 17 206 patients with cancer with NGS results from September 2015 to August 2021. A subset of patients have both bTMB and tTMB results. Statistical analyses are performed in R and include (1) correlation (r) and concordance (ρ) between patient-matched bTMB-tTMB pairs, (2) distribution of total bTMB and tTMB values, and (3) association of bTMB and tTMB with time to CPI therapy failure.ResultsIn 410 patient-matched bTMB-tTMB pairs, the median bTMB (m = 10.5 mut/Mb) was significantly higher than the median tTMB (m = 6.0 mut/Mb, P < .001) leading to conflicting “high” and “low” statuses in over one-third of cases at a threshold of 10 mut/Mb (n = 410). Significant differences were observed in the distribution of bTMB values from blood-NGS vendors, with guardant health (GH) reporting higher (m = 10.5 mut/Mb, n = 2183) than Foundation Medicine (FMI, m = 3.8 mut/Mb, n = 462, P < .001). bTMB from GH required a higher threshold (≥40 mut/Mb) than bTMB from FMI (≥12 mut/Mb) in order to be associated with CPI response.ConclusionsThis study uncovers variability in bTMB reporting among commercial NGS platforms, thereby evidencing a need for assay-specific thresholds in identifying patients who may respond to CPI therapy.

Identifying those patients who will benefit from immune checkpoint inhibitor therapy is a major challenge. This article assesses the concordance between blood tumor mutation burden (bTMB) and tissue tumor mutation burden (tTMB) from patients in real-world settings and compares associations with immune checkpoint inhibitor response.

Implications for PracticeIn patients with both blood- and tissue-based sequencing results, the median tumor mutation burden (TMB) is higher in blood (10.5 mutations per megabase) than in tissue (6.0 mutations per megabase). This discordance necessitates different thresholds for TMB from blood (≥40 mutations per megabase) and tissue (≥10 mutations per megabase) to be associated with response to immune checkpoint inhibition. A higher TMB threshold should be considered for certain commercial blood-based next-generation sequencing tests when determining potential benefit from immune checkpoint inhibition.     

Obesity-related Differential Gene Expression in the Visceral Adipose Tissue

Background:This study investigates the expression patterns in human adipose tissue, and identifies genes that may be involved in the abnormal energy homeostasis. Methods: Subjects were prospectively recruited from morbidly obese patients undergoing bariatric surgery and from non-obese organ donors. Extensive clinical data and visceral fat specimens were obtained from each subject at the time of surgery. A group of 50 obese patients and 9 non-obese controls were selected for further study. Two custom two-color cDNA microarrays were produced with 40,173 human individual cDNA clones. Microarray experiments were performed for each sample, and a selected group of gene expression values were confirmed with real-time RT-PCR. Results: A comparison of gene expression profiles from obese and non-obese patients identified 1,208 genes with statistically significant differential expression between the 2 groups. Most prominent among these genes are multiple glycolysis enzyme encoding genes; others are involved in oxysterol biosynthesis and signaling, or are ATP-binding transporters and solute carriers. Conclusion: Differential gene expression in the adipose tissue of morbidly obese patients includes genes related to lipid and glucose metabolism, membrane transport, and genes promoting the cell cycle. These findings are a first step toward clarifying the molecular pathogenesis of obesity and identifying potential targets for therapeutic intervention.     

Critical difference table for word recognition testing derived using computer simulation.

PURPOSE: To construct a table for upper and lower limits of the 95% critical range for changes in word recognition scores obtained with monosyllabic word lists (of lengths 10, 25, 50, and 100 words) using newly available methods. Although such a table has been available for nearly 30 years (A. R. Thornton & M. J. M. Raffin, 1978), the earlier table was constructed by calculation and used an approximation to the variance of the difference score between 2 administrations of word lists of identical size. It has been used clinically, reproduced, and recommended for use by clinicians in handbooks and textbooks. METHOD: The new table was created using computer simulation of the relevant distributions and a direct estimate of the variance of the difference score between 2 tests, calculated using the simulated results. RESULTS: The new table differed from the previous table in 23% of entries. Critical ranges were both narrowed (82%) and expanded (18%). No range changed by more than 1 word correct in any direction. The original table was most accurate for list sizes of 25 words each. CONCLUSION: Using the new table will provide more accurate estimates of the 95% critical range for successive administrations of word recognition tests.     

A multinomial model for identifying significant pure-tone threshold shifts.

PURPOSE: Significant threshold differences on retest for pure-tone audiometry are often evaluated by application of ad hoc rules, such as a shift in a pure-tone average or in 2 adjacent frequencies that exceeds a predefined amount. Rules that are so derived do not consider the probability of observing a particular audiogram. METHODS: A general solution for evaluating threshold differences on retest was developed on the basis of multinomial probabilities. The model uses the standard deviation of inter-test differences for 1 frequency as a parameter of the underlying Gaussian distribution of test results. The number of test frequencies, the categories of threshold change, and the probability of each category's occurrence are used to calculate the probability that a given pattern of threshold differences on retest (or 1 rarer) could occur by chance. RESULTS: The multinomial model was compared with 2 other methods for identifying threshold shifts in persons exposed to high sound pressure levels during concerts. The multinomial model identified the same audiograms as the ad hoc methods. CONCLUSION: Tables developed using a multinomial model can provide a clinical tool for evaluating audiograms by identifying statistically significant patterns of test-retest differences in hearing thresholds.     

A comparison of psychometric functions for detection in normal-hearing and hearing-impaired listeners

Psychometric functions (PFD) for the detection of pure tones were obtained with a two-interval forced-choice procedure from a group of listeners with normal hearing and a group of listeners with sensorineural impairments of presumed cochlear origin. Five PFDs were obtained for each group at each of the four test frequencies (500, 2000, 4000, and 8000 Hz). The slopes of PFDs were abnormally steep in some of the hearing-impaired listeners, but were statistically significant only at 2000 Hz.