Impact of the COVID-19 pandemic on the incidence of intussusception: a systematic review.

OBJECTIVE: We aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of intussusception. MATERIALS AND METHODS: Literature search of the PubMed and EMBASE databases was conducted for articles published in English until August 5, 2022. RESULTS: Overall, 127 articles were retrieved, and five studies from South Korea (n=4) and the United States of America (n=1) containing clinical data from single-center medical records to nationwide databases were ultimately included in the systematic review. All the included studies reported that the incidence of intussusception decreased significantly during the pandemic period compared with the pre-pandemic period. The communicable disease incidence tended to decrease even as the incidence of non-communicable diseases did not significantly change. There was no significant difference in the time to diagnosis between the pre-pandemic and pandemic periods; however, the time to radiologic reduction was significantly longer or not depending on the study. CONCLUSIONS: The COVID-19 pandemic significantly reduced the incidence of intussusception in children, supporting the hypothesis that infection plays a major role in the etiology of intussusception. Future studies in the late pandemic or post-pandemic era, which would represent the level of implementation of non-pharmaceutical interventions and social distancing as well as additional data from various countries will be needed.

Nosocomial outbreak of Achromobacter spp. bacteremia due to germicide contamination: a systematic review.

OBJECTIVE: Achromobacter spp. are aerobic, non-fermentative Gram-negative bacilli that can be widely found in aquatic environments. Nosocomial outbreaks and pseudo-outbreaks of Achromobacter spp. bacteremia have been recognized for decades. Notably, commonly used germicides in hospital settings constitute important sources for these outbreaks. This review aims at summarizing the latest studies and presents the characteristics of nosocomial outbreaks of Achromobacter spp. bacteremia caused by germicide contamination. MATERIALS AND METHODS: A systematic search of the PubMed and EMBASE databases was conducted for articles published in English between January 1, 2000, and June 10, 2022. RESULTS: Overall, 170 articles were retrieved, and 7 studies were finally included in the systematic review. Whether true or pseudo-bacteremia, positive blood culture results were most commonly reported in immunosuppressed patients or those with indwelling catheters. The most commonly reported contaminated germicide was chlorhexidine solution used as both an antiseptic and disinfectant. Atomizers, dispensers, and various product containers were identified as reservoirs. The prognoses of the affected patients were generally favorable. CONCLUSIONS: Awareness about the high survival ability of Achromobacter spp. in germicides and the possible hospital reservoirs of these microbes will help to improve infection control and prevent nosocomial outbreaks or pseudo-outbreaks caused by Achromobacter spp.

Using the lactate-to-albumin ratio to predict mortality in patients with sepsis or septic shock: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate whether the lactate-to-albumin ratio (LAR) can predict mortality in patients with sepsis or septic shock. PATIENTS AND METHODS: A systematic search of the PubMed, EMBASE, Web of Science, and Google Scholar databases was conducted on December 16, 2021, for relevant articles that provided the predictive performance of LAR for mortality in patients with sepsis or septic shock. RESULTS: Eight studies encompassing a total of 4,723 patients were included in this paper. The pooled sensitivity, specificity, and diagnostic odds ratio of the LAR for predicting mortality were 0.71 (95% confidence interval [CI]: 0.54-0.84), 0.68 (95% CI: 0.58-0.76) and 5.23 (95% CI: 2.62-10.45), respectively. The area under the summary receiver operating characteristic curve was 0.74 (95% CI: 0.70-0.78). CONCLUSIONS: The current evidence suggests that LAR is moderately predictive of mortality among patients with sepsis or septic shock and may be beneficial to identify high-risk patients.

Neutrophil-to-lymphocyte ratio for the diagnosis of pediatric acute appendicitis: a systematic review and meta-analysis.

OBJECTIVE: Acute appendicitis (AA) is one of the most common surgical emergencies and causes of acute abdominal pain in the pediatric population. However, it can be difficult to diagnose in children. We aimed to provide updated evidence on the diagnostic utility of the neutrophil-to-lymphocyte ratio (NLR) for AA, along with other conventional biomarkers, in pediatric patients. MATERIALS AND METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for eligible articles published up to May 16, 2021. RESULTS: We included 19 studies comprising a total of 5,974 pediatric cases. The overall sensitivity and specificity of the NLR were 0.82 (95% confidence interval [CI]: 0.79-0.85) and 0.76 (95% CI: 0.69-0.81), respectively. The overall diagnostic odds ratio was 14.34 (95% CI: 9.05-22.73). The area under the summary receiver operating characteristic curve was 0.86 (95% CI: 0.83-0.89). The pooled sensitivity and specificity of other biomarkers were as follows: 0.79 (95% CI: 0.71-0.86) and 0.66 (95% CI: 0.54-0.77) for the white blood cell count, 0.73 (95% CI: 0.69-0.77) and 0.68 (95% CI: 0.55-0.79) for the C-reactive protein level, 0.75 (95% CI: 0.65-0.82) and 0.78 (95% CI: 0.72-0.83) for the absolute neutrophil count, and 0.83 (95% CI: 0.79-0.87) and 0.68 (95% CI: 0.53-0.80) for the neutrophil percentage, respectively. CONCLUSIONS: The NLR has moderate predictive power for AA and can be used as a simple, auxiliary tool for diagnosis. NLR can also help clinicians decide whether to perform imaging testing when the clinical symptoms or physical examination findings are vague.

Effects of ultraviolet-filters on Daphnia magna development and endocrine-related gene expression.

Ultraviolet (UV) filters are emerging contaminants of concern that are widely spread throughout the aquatic environment. Many organic UV filters are endocrine disrupting compounds (EDCs) in vertebrates. However, few studies have assessed their effects on invertebrates. Molting, or the shedding of the exoskeleton, may be affected by exposure to these compounds in Arthropods (the largest phylum of invertebrates). Molting is necessary for growth and development and is regulated by an arthropod specific endocrine system, the ecdysteroid pathway. Alterations of this process by EDCs can result in improper development, reduced growth, and even death. We investigated the sublethal effects of chronic exposure to three organic UV filters (4-methylbenzylidene camphor (4MBC), octylmethoxycinnamate (OMC), and benzophenone-3 (BP3) in a crustacean, Daphnia magna, with particular emphasis on molting and development. We demonstrate that 4MBC, OMC, and BP3 affect development and long-term health in neonates of exposed parents at concentrations of 130 µg/L, 75 µg/L, and 166 µg/L, respectively. Additionally, the expression of endocrine-related genes (including ultraspiracle protein, usp) are significantly altered by 4MBC and BP3 exposure, which may relate to their developmental toxicity.

Point-of-care testing for the detection of SARS-CoV-2: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of the Food and Drug Administration Emergency Use Authorization (FDA-EUA) authorized point-of-care tests (POCTs) for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MATERIALS AND METHODS: A systematic literature search was conducted using the PubMed, Embase, and Web of Science databases for articles published till August 10, 2020. We included studies providing information regarding diagnostic test accuracy of FDA-EUA POCTs for SARS-CoV-2 detection. The methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The review protocol is registered in the International Prospective Register of Systematic Reviews (protocol number CRD42020202248). RESULTS: We included 26 studies describing a total of 3242 samples. The summary sensitivity and specificity were 0.94 [95% confidence interval (CI): 0.88-0.97] and 1.00 (95% CI: 0.99-1.00), respectively. The area under the summary receiver operating characteristic curve was 1.00 (95% CI: 0.99-1.00). A pooled analysis based on the index test revealed a summary sensitivity and specificity of Cepheid Xpert Xpress SARS-CoV-2 [0.99 (95% CI: 0.97-1.00) and 0.99 (95% CI: 0.94-1.00, respectively)] and ID NOW COVID-19 [0.78 (95% CI: 0.74-0.82) and 1.00 (95% CI: 0.98-1.00), respectively]. CONCLUSIONS: FDA-EUA POCTs, especially molecular assays, have high sensitivity, specificity, and overall diagnostic accuracy for detecting SARS-CoV-2. If approved, FDA-EUA POCTs can provide a rapid and practical way to identify infected individuals early on and help to limit the strain on the healthcare system. However, more high-quality clinical data are required to support our results.

Bronchovascular bundle thickening on CT as a predictor of survival and brain metastasis in patients with stage IA peripheral small cell lung cancer.

AIM: To determine if bronchovascular bundle (BVB) thickening on pretreatment computed tomography (CT) images helps predict survival in patients with peripheral small cell lung cancer (pSCLC) ≤3 cm. MATERIALS AND METHODS: The pretreatment CT examinations of 79 histopathologically proven pSCLC ≤3 cm (TNM stage I, 21; II, 13; III, 22; IV, 23) were reviewed retrospectively. The CT characteristics of the nodule and associated findings, including BVB thickening, were evaluated. Progression-free survival (PFS), overall survival (OS), and brain metastasis-free survival were compared with the presence of BVB thickening using Kaplan-Meier and Cox regression analysis. RESULTS: Among the 79 patients, 34 (43%) had BVB thickening. BVB thickening was prevalent in patients with mediastinal lymph node metastasis (50.9% versus 22.7%; p=0.024) and distant metastasis (60.9% versus 35.7%; p=0.049). Out of the 21 patients with TNM stage IA disease, the 16 patients (76.2%) without BVB thickening showed better PFS, OS, and brain metastasis-free survival (mean, 1,762 versus 483 days; p=0.019: 2,243 versus 1,328 days; p=0.038: 2,274 versus 1,287 days; p=0.038, respectively). Multivariate Cox regression analysis showed that the absence of BVB thickening (hazard ratio [HR], 7.806; 95% CI, 1.241-49.091; p=0.029) and surgery (HR, 0.075; 95% CI, 0.008-0.746; p=0.027) were independent and useful prognostic factors for PFS. CONCLUSIONS: BVB thickening was found more frequently in patients with advanced-stage pSCLC ≤3 cm, and the PFS was more favourable in patients without BVB thickening, with a similar tendency to that of OS and brain metastasis-free survival, in stage IA pSCLC.

Clinical outcomes of 201 neonates born to mothers with COVID-19: a systematic review.

OBJECTIVE: To evaluate the clinical manifestations and outcomes of neonates born to women who had Coronavirus Disease 2019 (COVID-19) during pregnancy. MATERIALS AND METHODS: A systematic literature search was conducted on PubMed and Embase till April 15, 2020, by combining the terms (COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, Novel Coronavirus, 2019-nCov, Wuhan pneumonia) and (pregnancy, pregnant women, mother, fetus, neonate, newborn, infant). RESULTS: We included 16 case series and 12 case reports describing a total of 223 pregnant women and 201 infants. Four newborns born to mothers affected by COVID-19 were reported to have laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection within 48 hours after birth. However, Reverse Transcription-Polymerase Chain Reaction tests of the breast milk, placenta, amniotic fluids, and cord blood and maternal vaginal secretions were all negative for SARS-CoV-2 in the reported cases. Fetal death was reported in two cases, and 48 of 185 newborns (25.9%) were born prematurely. Infants born small for gestational age and low birth weight (< 2,500 g) accounted for 8.3% and 15.6% of reported cases, respectively. Birth asphyxia and respiratory distress syndrome were observed in 1.8% and 6.4% of neonates, respectively. There was one neonatal death due to intractable gastric bleeding among the SARS-CoV-2-negative infants. CONCLUSIONS: Current evidence suggests that COVID-19 during pregnancy rarely affects fetal and neonatal mortality, but can be associated with adverse neonatal morbidities. Vertical transmission has not been observed in the majority of the reported cases. The infants born to mothers with COVID-19 are carefully monitored for accompanying complication, and quarantine of infected mothers is warranted.

Radiological features and progression of incipient active pulmonary tuberculosis according to risk factors.

To examine the radiological features of incipient active pulmonary tuberculosis (PTB) in humans and evaluate radiological progression according to risk factors. We retrospectively included 66 non-human immunodeficiency virus patients with bacteriologically proven PTB who had diagnostic and incidental pre-diagnostic computed tomography (CT) scans. CT scans were reviewed using a scoring system that included typical and atypical abnormalities associated with PTB. Risk factors for progression were assessed and, based on these, the CT features and progression of TB were compared using regression analyses. The most prevalent CT finding in incipient PTB was a well-defined solid nodule in upper lobes and lower lobe superior segments. The non-risk and at-risk groups did not differ in terms of the proportion of individuals with nodules and segmental location. The at-risk group had a higher incidence of progression (adjusted odds ratio 8.59), greater increment in the CT score (adjusted regression coefficient [aRC] 9.19) and a higher proportion of atypical CT abnormalities on diagnostic CT scans (aRC 13.15). Incipient active PTB primarily manifested as a small nodule in humans regardless of risk factors. With risk factors, it progressed more frequently and rapidly into active disease, with a higher prevalence of atypical radiological manifestations. .

Inflammatory cytokines and mononuclear cells in sudden sensorineural hearing loss.

OBJECTIVE: This study evaluated tumour necrosis factor-α, interleukins 10 and 12, and interferon-γ levels, peripheral blood mononuclear cells, and clusters of differentiation 17c and 86 expression in unilateral sudden sensorineural hearing loss. METHODS: Twenty-four patients with unilateral sudden sensorineural hearing loss, and 24 individuals with normal hearing and no history of sudden sensorineural hearing loss (who were attending the clinic for other problems), were enrolled. Peripheral blood mononuclear cells, and clusters of differentiation 11c and 86 were isolated and analysed. Plasma and supernatant levels of tumour necrosis factor-α, interferon-γ, and interleukins 10 and 12 were measured. RESULTS: There were no significant differences with respect to age and gender. Monocyte population, mean tumour necrosis factor-α level and cluster of differentiation 86 expression were significantly increased in the study group compared to the control group. However, interferon-γ and interleukin 12 levels were significantly decreased. The difference in mean interleukin 10 level was not significant. CONCLUSION: Increases in tumour necrosis factor-α level and monocyte population might play critical roles in sudden sensorineural hearing loss. This warrants detailed investigation and further studies on the role of dendritic cells in sudden sensorineural hearing loss.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions Associated With Low-Osmolar Iodinated Contrast Media: A Longitudinal Study Based on a Real-Time Monitoring System.

OBJECTIVES: We investigated the incidence of immediate hypersensitivity reaction (HSR) caused by different types of low-osmolar contrast media (LOCM) and cumulative exposure to LOCM. METHODS: This cohort study included all consecutive patients who underwent LOCM-enhanced computed tomography from 2012 through 2014. We assessed 5 LOCM (iobitridol, iohexol, iomeprol, iopamidol, and iopromide). All patients were monitored for adverse events, and new symptoms and signs were recorded in real time using the Contrast Safety Monitoring and Management System (CoSM2oS). RESULTS: The overall incidence of immediate HSR to LOCM was 0.97% (2004 events resulting from 205 726 exposures). Incidence differed significantly depending on whether the patient had a previous history of HSR to LOCM (0.80% in patients with no history and 16.99% in patients with a positive history of HSR to LOCM, P=.001). The incidence of HSR to individual LOCM ranged from 0.72% (iohexol) to 1.34% (iomeprol), although there were no significant differences across the 5 LOCM. A longitudinal analysis demonstrated that the incidence of HSR increased gradually with more frequent previous exposure to LOCM (HR=2.006 [95%CI, 1.517-2.653], P<.001). However, this cumulative increase in risk was observed in patients who had experienced HSR to LOCM, but not in those who had not. CONCLUSION: The incidence of HSR did not differ significantly across the 5 LOCM assessed in the study. Repeated exposure to LOCM did not increase the risk of HSR among patients who had never experienced HSR to LOCM.

Randomised trial comparing forced-air warming to the upper or lower body to prevent hypothermia during thoracoscopic surgery in the lateral decubitus position.

BACKGROUND: In the supine position, forced-air warming is more effective on the lower body than on the upper body to prevent intraoperative hypothermia. However, it is unknown in the lateral decubitus position. We thus compared forced-air warming on the upper and lower bodies in the lateral position. METHODS: Patients (n=123) were randomised to receive forced-air warming on the upper body or lower body during thoracoscopic surgery in the lateral position. We measured the nasopharyngeal temperature at 0, 30, 60, 90, and 120 min after lateral positioning during surgery and the infrared tympanic membrane temperature at 0, 30, 60, 90, and 120 min after surgery. Patients received both upper and lower body warming at a temperature of <35.5°C. The primary outcome was the incidence of intraoperative hypothermia with a temperature of <36.0°C. RESULTS: Intraoperative hypothermia was less frequent with the upper body warming than with the lower body warming {21/62 vs 35/61, risk ratio [95% confidence interval (CI)] 0.6 (0.4-0.9), P=0.011}. The intraoperative temperature was higher with the upper body warming than with the lower body warming at 30 (P=0.002), 60 (P<0.001), and 90 (P<0.001) min after lateral positioning, and the postoperative temperature was higher at 0 (P<0.001) and 30 (P=0.001) min after surgery. Fewer patients received both upper and lower body warming in the upper body warming group than in the lower body warming group during surgery (1 vs 7, P=0.032). CONCLUSIONS: Forced-air warming was more effective on the upper body than on the lower body to prevent hypothermia during thoracoscopic surgery in the lateral decubitus position. CLINICAL TRIAL REGISTRATION: NCT02993666.

Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration.

Metabolic diseases affect various organs including the brain. Accumulation or depletion of substrates frequently leads to brain injury and dysfunction. Deficiency of aminopeptidase P1, a cytosolic proline-specific peptidase encoded by the Xpnpep1 gene, causes an inborn error of metabolism (IEM) characterized by peptiduria in humans. We previously reported that knockout of aminopeptidase P1 in mice causes neurodevelopmental disorders and peptiduria. However, little is known about the pathophysiological role of aminopeptidase P1 in the brain. Here, we show that loss of aminopeptidase P1 causes behavioral and neurological deficits in mice. Mice deficient in aminopeptidase P1 (Xpnpep1-/- ) display abnormally enhanced locomotor activities in both the home cage and open-field box. The aminopeptidase P1 deficiency in mice also resulted in severe impairments in novel-object recognition, the Morris water maze task, and contextual, but not cued, fear memory. These behavioral dysfunctions were accompanied by epileptiform electroencephalogram activity and neurodegeneration in the hippocampus. However, mice with a heterozygous mutation for aminopeptidase P1 (Xpnpep1+/- ) exhibited normal behaviors and brain structure. These results suggest that loss of aminopeptidase P1 leads to behavioral, cognitive and neurological deficits. This study may provide insight into new pathogenic mechanisms for brain dysfunction related to IEMs.

Risk factors for suboptimal drug concentration of posaconazole oral suspension in patients with hematologic malignancy.

Absorption of posaconazole oral suspension is influenced by several factors including diet, medications, and mucosal integrity. However, there are few prospective data about which is the most important modifiable factor in routine clinical practice. We prospectively analyzed clinical risk factors associated with low posaconazole trough concentrations in 114 patients receiving anticancer chemotherapy due to acute myeloid leukemia or myelodysplastic syndrome who received posaconazole oral suspension. In multivariate analyses, risk factors for drug level<500ng/mL included low calorie intake, mucositis≥grade 2, H2 blocker famotidine and proton-pump inhibitor. The only significant risk factor for drug level<700ng/mL was famotidine use (adjusted relative risk, 3.18; 95% confidence interval, 1.07-9.11; P=0.038). In conclusion, medication of H2 blocker famotidine should be cautious in patients with hematologic malignancy receiving posaconazole suspension.

Extracorporeal Life Support as a Bridge to Lung Transplantation in Patients With Acute Respiratory Failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is being used more often as a bridge to transplantation (BTT) in patients with acutely decompensated end-stage lung disease in Korea. ECMO as a BTT may be the only rescue strategy for severe acute respiratory failure, but many centers still consider it to be a relative contraindication to lung transplantation because of its poor outcome. Because there are not enough lung donors, it is important to determine their optimal use. We reviewed and analyzed our experiences with the use of ECMO as a BTT in patients with acute respiratory failure. METHODS: This was a retrospective analysis of all patients with acutely decompensated end-stage lung disease treated with ECMO as a bridge to lung transplantation between March 2012 and February 2016. RESULTS: Of the 194 patients who underwent respiratory ECMO over a 4-year period, a BTT strategy was used for 19 patients (median age, 58 years) on our institution's lung transplantation waiting list (15 veno-venous, 3 veno-veno-arterial, 1 veno-arterial). Fourteen patients (73.7%) were successfully bridged to transplantation; however, 3 died while on the waiting list and 2 returned to their baseline functions without transplantation. The overall in-hospital survival rate was 57.9% (11 of 19), including the 9 (64.3%) patients who underwent transplantation. CONCLUSIONS: Our findings support the view that well-selected candidates with acutely decompensated end-stage lung disease may be safely bridged until a suitable donor is identified. ECMO is not able to reverse the course of patients; however, it could be a life-saving option for patients with acute respiratory failure requiring lung transplantation.

A novel K+ competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomised clinical study in healthy volunteers.

BACKGROUND: YH4808, a K+ -competitive acid blocker, is under clinical development for the treatment of acid-related disorders, such as gastroesophageal reflux disease. AIMS: To determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH4808, compared to placebo and esomeprazole. METHODS: This double-blind, randomised, placebo- and active comparator (esomeprazole)-controlled study was conducted with 123 healthy male volunteers. We evaluated YH4808 (30-800 mg) properties, administered in single (N=55) and multiple (N=24) oral doses, and recorded the effects on 24-hour intragastric acidity. Results were compared to placebo (N=20) and esomeprazole 40 mg (N=24). RESULTS: Plasma YH4808 exposure increased dose-proportionally and declined in a multi-phasic manner. YH4808 ≥200 mg/d maintained intragastric acidity at pH >4 for longer times than esomeprazole during both day and night (%Time at pH >4: >70% vs 58% of a 24-hour period, respectively; and >50% vs 33% of a 9-hour night respectively). A twice-daily regimen of YH4808 more effectively controlled intragastric pH at night than a once-daily regimen. In evaluating the mean areas under the intragastric pH-time curves in 15-minute intervals for 2 hours after dosing, we found that YH4808 had a faster onset than esomeprazole. Moreover, unlike esomeprazole, YH4808 PK and PD were not significantly affected by the CYP2C19 genotype of the subjects. YH4808 was well-tolerated at all doses administered. CONCLUSION: This study showed that YH4808 produced a rapid, sustained suppression of gastric secretion with good tolerability. The results at YH4808 ≥200 mg/d provide a rationale for further clinical investigations in populations with acid-related diseases.

On the mechanical behaviour of PEEK and HA cranial implants under impact loading.

The human head can be subjected to numerous impact loadings such as those produced by a fall or during sport activities. These accidents can result in skull fracture and in some complex cases, part of the skull may need to be replaced by a biomedical implant. Even when the skull is not damaged, such accidents can result in brain swelling treated by decompressive craniectomy. Usually, after recovery, the part of the skull that has been removed is replaced by a prosthesis. In such situations, a computational tool able to analyse the choice of prosthesis material depending on the patient's specific activity has the potential to be extremely useful for clinicians. The work proposed here focusses on the development and use of a numerical model for the analysis of cranial implants under impact conditions. In particular, two main biomaterials commonly employed for this kind of prosthesis are polyether-ether-ketone (PEEK) and macroporous hydroxyapatite (HA). In order to study the suitability of these implants, a finite element head model comprising scalp, skull, cerebral falx, cerebrospinal fluid and brain tissues, with a cranial implant replacing part of the skull has been developed from magnetic resonance imaging data. The human tissues and these two biocompatible materials have been independently studied and their constitutive models are provided here. A computational model of the human head under impact loading is then implemented and validated, and a numerical comparison of the mechanical impact response of PEEK and HA implants is presented. This comparison was carried out in terms of the effectiveness of both implants in ensuring structural integrity and preventing traumatic brain injury. The results obtained in this work highlight the need to take into account environmental mechanical considerations to select the optimal implant depending on the specific patient: whereas HA implants present attractive biointegration properties, PEEK implant can potentially be a much more appropriate choice in a demanding mechanical life style. Finally, a novel methodology is proposed to assess the need for further clinical evaluation in case of impact with both implants over a large range of impact conditions.

Vertebral bone attenuation on low-dose chest CT: quantitative volumetric analysis for bone fragility assessment.

This study evaluated the use of low-dose chest computed tomography (LDCT) for detecting bone fragility. LDCT-measured vertebral bone attenuation by volumetric methods showed good correlation with bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA, and good diagnostic performance for identifying osteoporosis and compression fractures. The results of this study suggest the feasibility of obtaining comprehensive information on bone health in subjects undergoing LDCT. INTRODUCTION: Osteoporosis is a prevalent but underdiagnosed disease that increases fracture risk. This study evaluated the utility of vertebral attenuation derived from low-dose chest computed tomography (LDCT) compared to dual-energy x-ray absorptiometry (DXA) for detecting bone fragility. METHODS: A total of 232 subjects (78 men and 154 women) aged above 50 years who underwent both LDCT and DXA within 30 days were evaluated. LDCT-measured bone attenuation in Hounsfield units (HU) of four vertebrae (T4, T7, T10, and L1) was evaluated using volumetric methods for correlation with DXA-measured bone mineral density (BMD) and for the diagnosis of compression fractures, osteoporosis, and low BMD (osteoporosis or osteopenia) in men and women, with DXA measurements as the reference standard. RESULTS: The average attenuation of the four vertebrae showed strong correlation with DXA-measured BMD of the lumbar spine (r = 0.726, p < 0.05). In receiver-operating characteristic (ROC) analyses, the area under the curve (AUC) across LDCT-measured thresholds of the average attenuation to distinguish compression fractures was 0.827, and a threshold of 129.5 HU yielded 90.9 % sensitivity and 64.4 % specificity. Similarly, average attenuation showed high AUCs and good diagnostic performance for detecting osteoporosis and low BMD in both men and women. Among 44 subjects with compression fractures, the average bone attenuation showed strong negative correlation with both the worst fracture grade (r = -0.525, p < 0.05) and cumulative fracture grade score (r = -0.633, p < 0.05). CONCLUSION: LDCT-measured bone attenuation by volumetric methods showed good correlation with BMD measured by DXA and good diagnostic performance for identifying bone fragility.

Exploration of Biomarkers for Amoxicillin/Clavulanate-Induced Liver Injury: Multi-Omics Approaches.

To explore potential biomarkers for amoxicillin/clavulanate-induced liver injury (AC-DILI), we conducted a clinical trial in 32 healthy subjects based on multi-omics approaches. Every subject was administered amoxicillin/clavulanate for 14 days. The liver-specific microRNA-122 (miR-122) level increased prior to and correlated well with the observed alanine aminotransferase (ALT) level increase. This result indicates its potential as a sensitive early marker for AC-DILI. We also identified urinary metabolites, such as azelaic acid and 7-methylxanthine, with levels that significantly differed among the groups classified by ALT elevation level on day 8 after drug administration (P < 0.05). Lymphocyte proliferation in response to the drug was also observed. These findings demonstrate sequential changes in the process of AC-DILI, including metabolic changes, increased miR-122 level, increased liver enzyme activity, and enhanced lymphocyte proliferation after drug administration. In conclusion, this study provides potential biomarkers for AC-DILI based on currently known mechanisms using comprehensive multi-omics approaches.

Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans.

We hypothesized that the pharmacodynamic (PD) characteristics of metformin would change with inhibition of the multidrug and toxin extrusion (MATE) transporter, which mediates renal elimination of metformin. Twenty healthy male subjects received two doses (750/500 mg) of metformin, with and without 50 mg of pyrimethamine (a potent MATE inhibitor), with 1 week of washout in between each dose. The PD characteristics of metformin were assessed using oral glucose tolerance tests (OGTTs) before and after the metformin dose. Metformin concentrations in plasma and urine were determined using liquid chromatography-electrospray ionization-tandem mass spectrometry. When metformin was co-administered with pyrimethamine, its area under the concentration-time curve from 0 to 12 h was 2.58-fold greater (p < 0.05), whereas the antihyperglycaemic effects of metformin were decreased. The mean differences (90% confidence interval) in mean and maximum serum glucose concentrations and in 2-h-post-OGTT serum glucose concentration were -0.6 (-1, -0.2), -0.9 (-1.6, -0.3) and -0.5 (-1.1, 0.1) mmol/l, respectively. These findings indicate that the response to metformin is not only related to the plasma exposure of metformin but is also related to other factors, such as inhibition of uptake transporters and the gastrointestinal-based pharmacology of metformin.