Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r = -0.407), but noise exposure effects are weak (r = -0.152). We conclude that noise exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r=-0.407), but noise-exposure effects are weak (r=-0.152). We conclude that noise-exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.

We aimed to assess the prognostic role of the neutrophil/lymphocyte ratio (NLR) in community-acquired pneumonia (CAP) via a single-center retrospective cohort of hospitalized adult patients from 1/2009 to 12/2019. Patients were dichotomized into lower NLR (≤12) and higher NLR (>12). The primary outcome was mortality. ICU admission and hospital- and ICU-free days were secondary outcomes. The pneumonia severity index (PSI) and the NLR\'s ability to predict outcomes was also tested. An NLR ≤12 was observed in 2513 (62.2%) patients and >12 in 1526 (37.8%). After adjusting for PSI, the NLR was not associated with hospital mortality (odds ratio [OR] 1.115; 95% confidence interval [CI] 0.774, 1.606; p = 0.559), but it was associated with a higher risk of ICU admission (OR 1.405; 95% CI 1.216, 1.624; p < 0.001). The PSI demonstrated acceptable discrimination for mortality (area under the receiver operating characteristic curve [AUC] 0.78; 95% CI 0.75, 0.82) which was not improved by adding the NLR (AUC 0.78; 95% CI 0.75, 0.82, p = 0.4476). The PSI\'s performance in predicting ICU admission was also acceptable (AUC 0.75; 95% CI 0.74, 0.77) and improved by including the NLR (AUC 0.76, 95% CI 0.74, 0.77, p = 0.008), although with limited clinical significance. The NLR was not superior to the PSI for predicting mortality in hospitalized CAP patients.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people living with HIV (PLWH) and the expression of some microRNAs could be useful as biomarkers for the diagnosis of NAFLD. The aim of this study was to identify patterns of differential expression of microRNAs in PLWH and assess their diagnostic value for NALFD.
A discovery case-control study with PLWH was carried out. The expression of miRNAs was determined using HTG EdgeSeq technology. Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, BMI, CD4+ lymphocyte count, active HCV infection, and ART regimen.
Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study.
Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.

In ischemic stroke, selectively cooling the ischemic penumbra might lead to neuroprotection while avoiding systemic complications. Because penumbral tissue has reduced cerebral blood flow and in vivo brain temperature measurement remains challenging, the effect of different methods of therapeutic hypothermia on penumbral temperature are unknown. We used the COMSOL Multiphysics® software to model a range of cases of therapeutic hypothermia in ischemic stroke. Four ischemic stroke models were developed with ischemic core and/or penumbra volumes between 33-300 mL. Four experiments were performed on each model, including no cooling, and intraarterial, intravenous, and active conductive head cooling. The steady-state temperature of the non-ischemic brain, ischemic penumbra, and ischemic core without cooling was 37.3 °C, 37.5-37.8 °C, and 38.9-39.4 °C respectively. Intraarterial, intravenous and active conductive head cooling reduced non-ischemic brain temperature by 4.3 °C, 2.1 °C, and 0.7-0.8 °C respectively. Intraarterial, intravenous and head cooling reduced the temperature of the ischemic penumbra by 3.9-4.3 °C, 1.9-2.1 °C, and 1.2-3.4 °C respectively. Active conductive head cooling was the only method to selectively reduce penumbral temperature. Clinical studies that measure brain temperature in ischemic stroke patients undergoing therapeutic hypothermia are required to validate these hypothesis-generating findings.

COVID-19 has been a diagnostic and therapeutic challenge. It has marked a paradigm shift when considering other types of pneumonia etiology. We analyzed the biomarkers related to endothelial damage and immunothrombosis in COVID-19 in comparison to community-acquired pneumonia (CAP) through a case-control study of 358 patients with pneumonia (179 hospitalized with COVID-19 vs. 179 matched hospitalized with CAP). Endothelial damage markers (endothelin and proadrenomedullin), neutrophil extracellular traps (NETs) (citrullinated-3 histone, cell-free DNA), and platelet activation (soluble P-selectin) were measured. In-hospital and 1-year follow-up outcomes were evaluated. Endothelial damage, platelet activation, and NET biomarkers are significantly higher in CAP compared to COVID-19. In-hospital mortality in COVID-19 was higher compared to CAP whereas 1-year mortality and cardiovascular complications were higher in CAP. In the univariate analysis (OR 95% CIs), proADM and endothelin were associated with in-hospital mortality (proADM: CAP 3.210 [1.698-6.070], COVID-19 8.977 [3.413-23.609]; endothelin: CAP 1.014 [1.006-1.022], COVID-19 1.024 [1.014-1.034]), in-hospital CVE (proADM: CAP 1.623 [1.080-2.439], COVID-19 2.146 [1.186-3.882]; endothelin: CAP 1.005 [1.000-1.010], COVID-19 1.010 [1.003-1.018]), and 1-year mortality (proADM: CAP 2.590 [1.644-4.080], COVID-19 13.562 [4.872-37.751]; endothelin: CAP 1.008 [1.003-1.013], COVID-19 1.026 [1.016-1.037]). In conclusion, COVID-19 and CAP showed different expressions of endothelial damage and NETs. ProADM and endothelin are associated with short- and long-term mortality.

BACKGROUND: Community-acquired pneumonia (CAP) represents one of the leading causes of hospitalization and has a substantial impact on the financial burden of healthcare. The aim of this study was to identify factors associated with the length of hospital stay (LOHS), rehospitalization and mortality of patients admitted for CAP.
METHODS: A retrospective cohort study was conducted with patients presenting to a Swiss public hospital between January 2019 and December 2019. Zero-truncated negative binomial and multivariable logistic regression analyses were performed to assess risk factors.
RESULTS: A total of 300 patients were analyzed (median 78 years, IQR [67.56, 85.50] and 53% males) with an average LOHS of 7 days (IQR [5.00, 9.00]). Of the 300 patients, 31.6% (97/300) were re-hospitalized within 6 months, 2.7% (8/300) died within 30 days and 11.7% (35/300) died within 1 year. The results showed that sex (IRR = 0.877, 95% CI = 0.776-0.992, p-value = 0.036), age (IRR = 1.007, 95% CI = 1.002-1.012, p-value = 0.003), qSOFA score (IRR = 1.143, 95% CI = 1.049-1.246, p-value = 0.002) and atypical pneumonia (IRR = 1.357, 95% CI = 1.012-1.819, p-value = 0.04) were predictive of LOHS. Diabetes (OR = 2.149, 95% CI = 1.104-4.172, p-value = 0.024), a higher qSOFA score (OR = 1.958, 95% CI = 1.295-3.002, p-value = 0.002) and rehabilitation after discharge (OR = 2.222, 95% CI = 1.017-4.855, p-value = 0.044) were associated with a higher chance of being re-hospitalized within 6 months, whereas mortality within 30 days and within one year were both associated with older age (OR = 1.248, 95% CI = 1.056-1.562, p-value = 0.026 and OR = 1.073, 95% CI = 1.025-1.132, p-value = 0.005, respectively) and the presence of a cancer diagnosis (OR = 32.671, 95% CI = 4.787-369.1, p-value = 0.001 and OR = 4.408, 95% CI = 1.680-11.43, p-value = 0.002, respectively).
CONCLUSIONS: This study identified routinely available predictors for LOHS, rehospitalization and mortality in patients with CAP, which may further advance our understanding of CAP and thereby improve patient management, discharge planning and hospital costs.

BACKGROUND: Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an acute hospital visit and to determine if the current treatment algorithm provided specific and sufficient coverage against Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae (LMC).
METHODS: A descriptive cross-sectional, multicenter study of all adults with an acute hospital visit in the Region of Southern Denmark between January 2016 and March 2018 was performed. Using medical records, we retrospectively identified the empirical antibiotic treatment and the microbiological etiology for CAP patients. CAP patients who were prescribed antibiotics within 24 h of admission and with an identified bacterial pathogen were included. The prescribed empirical antibiotic treatment and its ability to provide specific and sufficient coverage against LMC pneumonia were determined.
RESULTS: Of the 19,133 patients diagnosed with CAP, 1590 (8.3%) patients were included in this study. Piperacillin-tazobactam and Beta-lactamase sensitive penicillins were the most commonly prescribed empirical treatments, 515 (32%) and 388 (24%), respectively. Our analysis showed that 42 (37%, 95% CI: 28-47%) of 113 patients with LMC pneumonia were prescribed antibiotics with LMC coverage, and 42 (12%, 95% CI: 8-15%) of 364 patients prescribed antibiotics with LMC coverage had LMC pneumonia.
CONCLUSIONS: Piperacillin-tazobactam, a broad-spectrum antibiotic recommended for uncertain infectious focus, was the most frequent CAP treatment and prescribed to every third patient. In addition, the current empirical antibiotic treatment accuracy was low for LMC pneumonia. Therefore, future research should focus on faster diagnostic tools for identifying the infection focus and precise microbiological testing.

BACKGROUND: Community-acquired pneumonia (CAP) is usually diagnosed in children, and the type of respiratory specimen is critical. Differences in pathogens detection between induced sputum (IS) and bronchoalveolar lavage fluid (BALF) have not been evaluated.
METHODS: In 2018, paired sputum and BALF samples from CAP hospitalised children with indications for bronchoalveolar lavage (BAL) were subjected to multiplex PCR for the detection of 11 common respiratory pathogens.
RESULTS: A total of 142 children with paired sputum and BALF were tested. The overall positivity rate was 85.9% (122/142) for sputum and 80.3% (114/142) for BALF. The two specimens presented almost perfect agreement between the detection on M. pneumoniae, influenza A, influenza B, bocavirus and RSV. In contrast, adenovirus had the lowest kappa value of 0.156, and a false negative rate (FNR) of 66.7%. Rhinovirus had the highest false positive rate (FPR) as 18.5%. The consistent rate was significantly higher in school-age children than those under 1 year old (p = .005). Bacterial co-infection in BALF specimens were observed in 14.8% (21/142). Of the 11 discordant pairs of specimens, 9 cases were sputum(+)/BALF(-) with adenovirus predominating.
CONCLUSIONS: Our findings suggest that the consistency of results between sputum and BALF is pathogen specific. Careful consideration needs to be given to whether sputum can be used as a substitute for BALF when children are young or co-infections with bacteria are suspected.

Guidelines recommend intravenous (IV) ceftriaxone at a dose of 1-2 g/d as empirical treatment in adults hospitalized with community acquired pneumonia (CAP), with the addition of macrolide. We examined whether 1 g/d of IV ceftriaxone is associated with similar clinical outcomes to those of 2 g/d. This is a single-center, retrospective, cohort study of all adult patients hospitalized at Rabin Medical Center between 2015 and 2018 with CAP. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 2045 patients were treated with IV ceftriaxone 1 g/d and were and compared to 1944 patients who were treated with 2 g/d. The groups were comparable in their baseline characteristics and their clinical presentation. The 30-day all-cause mortality rate was similar between the groups (301/2045 (14.7%) for 1 g/d vs. 312/1944 (16.0%) for 2 g/d, p = 0.24). The rate of C. difficile infection (CDI) was significantly decreased with 1 g/d compared to 2 g/d (4/2045 (0.2%) vs. 12/1944 (0.6%), p = 0.03) and the length of stay was significantly shorter (median 4 days interquartile range (IQR) 3-7 vs. 5 days IQR 3-8, p = 0.02). None of the blood isolates of Streptococcus pneumoniae were penicillin or ceftriaxone resistant. For hospitalized patients with CAP, IV ceftriaxone 1 g/d was associated with similar mortality rates as IV ceftriaxone 2 g/d, with a decreased rate of CDI and shorter length of stay. Ceftriaxone 1 g/d may be sufficient to treat patients with CAP in countries with low prevalence of drug resistant Streptococcus pneumoniae.