Direct comparison of the diagnostic accuracy of 2-[18F]-fluoro-2-deoxy-d-glucose PET/CT and MRI for the differentiation of malignant peripheral nerve sheath tumour in neurofibromatosis type I: a meta-analysis.

AIM: To compare the diagnostic test of integrated 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG PET/CT) with that of magnetic resonance imaging (MRI) for the differentiation of malignant peripheral nerve sheath tumours (MPNSTs) in neurofibromatosis type 1 (NF1) patients. MATERIALS AND METHODS: A systematic search was performed in PubMed and EMBASE (last updated in 30 November 2022). Studies investigating the performance of FDG PET/CT and MRI for differentiation of MPNSTs were eligible for inclusion. Only studies reporting a direct comparison between these imaging methods were considered to establish precise summary estimates in the same setting of patients. RESULTS: The pooled estimate of sensitivity of FDG PET/CT was 0.99 and a pooled specificity of 0.53. The pooled estimate of sensitivity of MRI was 0.85 and a pooled specificity of 0.85. CONCLUSION: Analysis of the available studies indicated that FDG PET/CT and MRI had similar diagnostic performances for differentiation of MPNSTs in patients with NF1; however, either technique can be a complement to the other rather than being used singly.

Improved diagnostic performance of susceptibility-weighted imaging with compressed sensing-sensitivity encoding and neuromelanin-sensitive MRI for Parkinson's disease and atypical Parkinsonism.

AIM: To verify the diagnostic performance of the loss of nigrosome-1 on susceptibility-weighted imaging (SWI) with compressed sensing-sensitivity encoding (CS-SENSE) and neuromelanin on neuromelanin-sensitive (NM) magnetic resonance imaging (MRI) for the diagnosis of Parkinson's disease (PD) and atypical Parkinsonism. MATERIALS AND METHODS: A total of 195 patients who underwent MRI between October 2019 and February 2020, including SWI, with or without CS-SENSE, and NM-MRI, were reviewed retrospectively. Two neuroradiologists assessed the loss of nigrosome-1 on SWI and neuromelanin on the NM-MRI. The result of N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl) nortropane positron-emission tomography (PET) was set as the reference standard. RESULTS: When CS-SENSE was applied for nigrosome-1 imaging on SWI, the non-diagnostic scan rate was lowered significantly from 19.3% (17/88) to 5.6% (6/107; p=0.004). Diagnosis of PD and atypical Parkinsonism based on the loss of nigrosome-1 on SWI and based on NM-MRI showed good diagnostic value (area under the curve [AUC] 0.821, 95% confidence interval [CI] = 0.755-0.875: AUC 0.832, 95% CI = 0.771-0.882, respectively) with a substantial inter-reader agreement (κ = 0.791 and 0.681, respectively). Combined SWI and neuromelanin had a similar discriminatory ability (AUC 0.830, 95% CI = 0.770-0.880). Similarly, the diagnosis of PD was excellent. CONCLUSIONS: CS-SENSE may add value to the diagnostic capability of nigrosome-1 on SWI to reduce the nondiagnostic scan rates. Furthermore, loss of nigrosome-1 on SWI or volume loss of neuromelanin on NM-MRI may be helpful for diagnosing PD.

Efficacy and safety of shunt surgery in patients with idiopathic normal-pressure hydrocephalus: can we predict shunt response by preoperative magnetic resonance imaging (MRI)?

AIM: The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications. MATERIALS AND METHODS: A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response. RESULTS: Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response. CONCLUSION: Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients.

Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

Prevalence and disease burden of chronic cough in nine cities of China: an observational study.

BACKGROUND: Chronic cough (CC) is common in the general population of China, creating a difficult-to-ignore public health burden. However, there is a lack of research on the nationwide prevalence and disease burden of CC in the Chinese population. We aim to use an insurance claims database to assess the prevalence and the corresponding economic burden owing to CC in China. METHODS: This was a retrospective observational study based on an administrative medical insurance database in 2015, 2016 and 2017, from nine cities in North, South, East, South-West, and North-West regions of China. The study population was Chinese adults (≥ 18 years old) who had been identified as CC patients. Descriptive data analyses were used in statistical analysis. RESULTS: A total of 44,472, 55,565, and 56,439 patients with mean ages of 53.2 (16.3) years were identified as patients with CC in 2015, 2016, and 2017, respectively. Of these, 55.24% were women. In addition, 8.90%, 9.46%, and 8.37% of all patients in 2015, 2016, and 2017, who had applied for medical insurance, had CC, respectively, with a three-year average probability of 8.88%. The median number of outpatient visits within a calendar year was 27 per year due to any reason during the period of 2015-2017. The median medical cost of each patient per year increased from 935.30 USD to 1191.47 USD from 2015 to 2017. CONCLUSION: CC is common among medical insurance users, with a substantial utilization of medical resources, highlighting the huge burden of CC in China.

Changes in smoking patterns and characteristics of Koreans using the Korea National Health and Nutrition Examination Survey 2013-2021 data.

OBJECTIVES: This study explored factors related to Korean adults' smoking patterns and also the reasons for using new types of tobacco products. STUDY DESIGN: Cross-sectional survey. METHODS: Data from the Korea National Health and Nutrition Examination Survey from 2013 to 2021 were used. The prevalence of the use of electronic cigarettes (e-cigarettes) or heated tobacco products (HTPs) alone or in combination with conventional cigarettes (CC) and the reasons for using new tobacco products are presented. Factors associated with using new types of tobacco products alone or in combination with CC compared to exclusive CC users were identified using multinomial logistic regression analysis. RESULTS: The prevalence of current smoking was 25.54% in 2013 and 23.05% in 2021, with no significant change. The prevalence of CC decreased from 23.39% in 2013 to 15.77% in 2021. The prevalence of new tobacco use in combination with CC did not show a definite trend. The prevalence of exclusive use of new tobacco was <1% until 2018 and has rapidly increased thereafter. Of the HTPs users, 46.68% responded with 'no cigarette smell' as the main reason for HTPs use, followed by 'It seems less harmful than cigarette' (19.19%), and 'It seems to be helpful for quitting smoking' (15.04%). Of the e-cigarette users, 45.19% responded 'It seems to be helpful for quitting smoking' as the main reason for e-cigarette use, followed by 'It is less harmful than cigarettes' (19.98%). Compared to CC users, new tobacco users were younger, had a higher household income or education, and used more nutritional supplements. CONCLUSION: Regulations for newer tobacco products are more lenient than for traditional cigarettes, leading to misunderstandings, especially among women and young people. To increase awareness of the risks of these products, specific policies such as disclosure of ingredients, ban on online sales, and increase in consumption tax, are needed.

A retrospective analysis of nonresponse to denosumab after hip fractures.

Denosumab is an effective antiresorptive drug commonly prescribed for the treatment of osteoporosis. However, some patients do not respond well to denosumab treatment. The aim of this study was to evaluate the factors underlying treatment nonresponses to denosumab in elderly patients following hip fracture. This retrospective study included 130 patients treated with denosumab after osteoporotic hip fracture between March 2017 and March 2020. The patients were categorized as denosumab nonresponders if they had a T-score <-3 that persisted between dual-energy X-ray absorptiometry scans, a >3% decrease in bone mineral density (BMD), or an incident fracture on denosumab therapy. We examined the baseline characteristics associated with blunted BMD responses and compared the groups following denosumab treatment for 12 months. Of 130 patients with baseline data, 105 patients (80.8%) were considered responders. No difference in baseline vitamin D, calcium, BMI, age, gender, prior fracture history, or bisphosphonate use was observed between responders and nonresponders. A longer interval between denosumab injections was associated with suboptimal BMD response at both spine and total hip (p<0.001 and p=0.04, respectively). The overall L-BMD and H-BMD were significantly increased compared with pretreatment levels after denosumab treatment (5.7% and 2.5%, respectively). This study revealed that nonresponse was not strongly associated with certain baseline variables and it appears that the reponders and nonresponders were reasonably comparable in this study population. The results of our study highlight the importance of timely denosumab administration when using this drug for osteoporosis management. Physicians should keep these results in mind in clinical practice so that they can improve utilization of 6-month denosumab.

Cost-Effectiveness of Midazolam Versus Haloperidol Versus Olanzapine for the Management of Acute Agitation in the Accident and Emergency Department.

OBJECTIVES: A multicenter randomized clinical trial in Hong Kong Accident and Emergency (A&E) departments concluded that intramuscular (IM) olanzapine is noninferior to haloperidol and midazolam, in terms of efficacy and safety, for the management of acutely agitated patients in A&E setting. Determining their comparative cost-effectiveness will further provide an economic perspective to inform the choice of sedative in this setting. METHODS: This analysis used data from a randomized clinical trial conducted in Hong Kong A&E departments between December 2014 and September 2019. A within-trial cost-effectiveness analysis comparing the 3 sedatives was conducted, from the A&E perspective and a within-trial time horizon, using a decision-analytic model. Sensitivity analyses were also undertaken. RESULTS: In the base-case analysis, median total management costs associated with IM midazolam, haloperidol, and olanzapine were Hong Kong dollar (HKD) 1958.9 (US dollar [USD] 251.1), HKD 2504.5 (USD 321.1), and HKD 2467.6 (USD 316.4), respectively. Agitation management labor cost was the main cost driver, whereas drug costs contributed the least. Midazolam dominated over haloperidol and olanzapine. Probabilistic sensitivity analyses supported that midazolam remains dominant > 95% of the time and revealed no clear difference in the cost-effectiveness of IM olanzapine versus haloperidol (incremental cost-effectiveness ratio 667.16; 95% confidence interval -770.89, 685.90). CONCLUSIONS: IM midazolam is the dominant cost-effective treatment for the management of acute agitation in the A&E setting. IM olanzapine could be considered as an alternative to IM haloperidol given that there is no clear difference in cost-effectiveness, and their adverse effect profile should be considered when choosing between them.

Detection rate of MR myelography without intrathecal gadolinium in patients with newly diagnosed spontaneous intracranial hypotension.

AIM: To evaluate the detection rate of magnetic resonance (MR) myelography without intrathecal gadolinium for cerebrospinal fluid (CSF) leakage in patients with newly diagnosed spontaneous intracranial hypotension (SIH) and to validate a published scoring system for predicting CSF leakage. MATERIALS AND METHODS: This retrospective, observational, single-institution study included patients with newly diagnosed SIH between March 2015 and April 2021. Patients were included if they (a) had newly diagnosed SIH and (b) underwent initial brain MR imaging and preprocedural MR myelography with two- and three-dimensional turbo spin-echo sequences. Patients who underwent spine surgery or procedures including epidural injection and acupuncture were excluded. The detection rate was defined as the proportion of patients with a true-positive MR myelography result among all patients with confirmed CSF leakage. The interobserver agreement for the MR myelography results between two radiologists was analysed using weighted kappa statistics. RESULTS: A total of 136 patients (mean age, 48 years; 70 women) with suspected SIH were included. Of these patients, 120 (88%, 120/136) were confirmed to have CSF leakage. Of the patients with confirmed CSF leakage, 90 (75%, 90/120) had epidural fluid collection. The detection rate of MR myelography for CSF leakage was 88% (105/120). The interobserver agreement between the two readers for detecting CSF leakage (κ = 0.76) or epidural fluid collection (κ = 0.76) on MR myelography was high. Among 24 patients with normal brain MR imaging results, 16 had CSF leakage (67%, 16/24). CONCLUSIONS: Non-invasive MR myelography without intrathecal gadolinium should be considered to detect CSF leakage in patients with suspected SIH.

Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial.

BACKGROUND: Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR). PATIENTS AND METHODS: This phase I/II study (NCT03052933) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m2 on days 1 and 8) in 28-day cycles. RESULTS: Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders. CONCLUSION: The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.

Diagnostic test accuracy of 18F-FDG PET/CT for prediction of programmed death ligand 1 (PD-L1) expression in solid tumours: a meta-analysis.

AIM: To investigate the predictive value of integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) for the prediction of programmed death ligand 1 (PD-L1) expression in solid tumours via a systematic review and meta-analysis. MATERIALS AND METHODS: The PubMed, Cochrane, and EMBASE databases, from the earliest available date of indexing through 31 October 2020, were searched for studies evaluating the diagnostic performance of 18F-FDG PET/CT for prediction of PD-L1 expression in solid tumours other than lung cancer. RESULTS: Across seven studies (473 patients), the pooled sensitivity for 18F-FDG PET/CT was 0.75 (95% confidence interval [CI]: 0.65-0.82) without heterogeneity (I2 = 47.2, p=0.08) and a pooled specificity of 0.73 (95% CI: 0.64-0.81) with heterogeneity (I2 = 53.8, p=0.04). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 2.8 (95% CI: 2.1-3.7) and negative likelihood ratio (LR-) of 0.35 (95% CI: 0.26-0.47). The pooled diagnostic odds ratio (DOR) was 8 (95% CI: 5-13). Hierarchical summary receiver operating characteristic (ROC) curve and indicates that the area under the curve was 0.80 (95% CI: 0.77-0.84). CONCLUSION: The current meta-analysis showed a moderate sensitivity and specificity of 18F-FDG PET/CT for the prediction of PD-L1 expression in solid tumours. At present, the literature regarding the use of 18F-FDG PET/CT for the prediction of PD-L1 expression in solid tumours still limited; thus, further large multicentre studies would be necessary to substantiate the diagnostic accuracy of 18F-FDG PET/CT for prediction of PD-L1 expression in solid tumours.

Hearing loss is associated with cortical thinning in cognitively normal older adults.

BACKGROUND AND PURPOSE: Hearing loss (HL) is one of the most influential risk factors of dementia in older adults. However, its potential association with neurodegeneration is not well established. The association between HL and cortical thickness in cognitively normal older adults was evaluated. METHODS: In all, 982 cognitively normal older adults (age ≥65 years) were identified from the Health Promotion Center at the Samsung Medical Center from September 2008 to December 2014. The participants underwent pure-tone audiometry and brain magnetic resonance imaging. HL was evaluated according to a four-frequency (0.5, 1, 2, 4 kHz) pure-tone average. Participants were divided into three groups according to pure-tone average (normal hearing ≤15 dB, minimal HL 16-25 dB, mild-to-severe HL >25 dB). Cortical thickness in the HL groups was compared with that of the normal hearing group. RESULTS: In women, right ear HL was associated with cortical thinning: the minimal HL group showed cortical thinning in the left frontal and bilateral occipital areas and the mild-to-severe HL group showed cortical thinning in the bilateral frontal, right temporal and bilateral occipital areas compared to the normal hearing group. In men, there was no significant association between HL on either side and cortical thickness. CONCLUSION: In older women, right ear HL is associated with neurodegeneration even in a cognitively normal state. Therefore, managing HL especially in older women may be an effective strategy for dementia prevention.

Microbial contamination of tattoo and permanent makeup inks marketed in the US: a follow-up study.

In a 2018 survey, U.S. Food and Drug Administration (FDA) identified microbial contamination in 42 (49%) of 85 unopened tattoo and permanent makeup (PMU) inks purchased from 13 manufacturers in the US between November 2015 and April 2016. To confirm the results of our previous survey, we evaluated the level of microbial contamination in an additional 27 samples from 10 manufacturers from September 2017 to December 2017, including 21 unopened tattoo and PMU inks which were selected based on our previous survey results and 6 ink diluents that were not previously analysed. Aerobic plate count and enrichment culture methods from the FDA's Bacteriological Analytical Manual revealed 11 (52%) out of 21 inks, from six manufacturers, were contaminated with micro-organisms, with contamination levels up to 3·6 × 108  CFU per gram, consistent with our previous survey results. We identified 25 bacterial strains belonging to nine genera and 19 species. Strains of Bacillus sp. (11 strains, 44%) were dominant, followed by Paenibacillus sp. (5 strains, 20%). Clinically relevant strains, such as Kocuria rhizophila and Oligella ureolytica, were also identified, as similar to the findings in our previous survey. No microbial contamination was detected in any of the six ink diluents.

Association of blood n-3 fatty acid with bone mass and bone marrow TRAP-5b in the elderly with and without hip fracture.

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment. INTRODUCTION: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples. METHODS: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44). RESULTS: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (ß = 0.615, P = 0.002) and total femur (ß = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (ß = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates. CONCLUSIONS: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.

The role of 18F-fluciclovine PET in the management of prostate cancer: a systematic review and meta-analysis.

AIM: To investigate the diagnostic performance of 18F-fluciclovine positron-emission tomography (PET) or combined PET and computed tomography (PET/CT) for diagnosis of primary cancer, preoperative lymph node (LN) staging, and detection of recurrent disease of prostate cancer (PCa) through a systematic review and meta-analysis. MATERIALS AND METHODS: The PubMed and EMBASE databases were searched from the earliest available date of indexing through 31 December 2018, for studies evaluating the diagnostic performance of 18F-fluciclovine PET or PET/CT for the management of PCa patients. The sensitivities, specificities, and positive and negative likelihood ratios (LR+ and LR-) across the studies were calculated and summary receiver operating characteristic curves were constructed. RESULTS: Across 13 studies (563 patients), the pooled sensitivity for 18F-fluciclovine PET or PET/CT for diagnosis of primary PCa was 0.87 (95% confidence interval [CI]: 0.77-0.93) and a pooled specificity of 0.84 (95% CI: 0.68-0.93). For LN staging, the pooled sensitivity was 0.56 (95% CI: 0.37-0.74) and a pooled specificity of 0.98 (95% CI: 0.88-1.00). For detection of recurrent disease, the pooled sensitivity was 0.79 (95% CI: 0.60-0.91) and a pooled specificity of 0.69 (95% CI: 0.59-0.77). In meta-regression analysis, no definite variable was the source of the study heterogeneity. CONCLUSION: The current meta-analysis showed the moderate sensitivity and specificity of 18F-fluciclovine PET or PET/CT for the diagnosis of primary cancer, preoperative LN staging, and detection of recurrent PCa. Further large multicentre studies will be necessary to substantiate the diagnostic accuracy of 18F-fluciclovine PET/CT for management of PCa patients.

Extracellular production of functional single-chain variable fragment against aflatoxin B1 using Escherichia coli.

scFv-BM3 is a single-chain variable fragment (scFv) against aflatoxin B1 (AFB1 ) engineered by affinity maturation and site-directed mutagenesis, and thus has a 31-fold higher affinity than its wild-type. To apply scFv-BM3 to immunological detection of AFB1 , periplasmic expression in Escherichia coli was attempted to produce a functional form of scFv-BM3. scFv-BM3 accumulated as inactive aggregates in the cells. However, it was found that scFv-BM3 secreted into the culture medium had binding activity to AFB1 . Expression conditions for scFv-BM3 were further manipulated to enhance secretion into the culture medium. This extracellular secretion of functional scFv-BM3 was significantly improved by supplementation with Triton X-100 and optimization of expression conditions. The scFv-BM3 purified from the culture medium exhibited a typical antiparallel ß-sheet structure and adopted a proper conformation to bind AFB1 with high affinity and specificity in various biophysical and biochemical analyses. SIGNIFICANCE AND IMPACT OF THE STUDY: Single-chain variable fragments (scFvs) are recombinant antibodies that are difficult to produce as a functional form in Escherichia coli. This study demonstrates the production of functional scFvs against aflatoxin B1 (AFB1 ) (scFv-BM3) using Escherichia coli by extracellular secretion. While periplasmic expression of scFv-BM3 resulted in formation of inactive aggregates in E. coli, the scFv-BM3 secreted into the culture medium adopted a properly folded structure for specific binding to AFB1 . This study promotes the application of functional scFv-BM3 to the immunological detection of AFB1 in biotechnology fields.

Nasopharyngeal undifferentiated carcinoma with sarcomatoid features: Pitfalls in the immunohistochemistry.

We present a case of an undifferentiated subtype of non-keratinizing squamous cell carcinoma (NK-SCC) with sarcomatoid features in the nasopharynx in a 69-year-old man who was difficult to diagnose due to spindle-shaped malignant cells. He was admitted because of a right nasal obstruction and right headache, and imaging revealed a heterogeneously enhanced irregularly shaped mass at the nasopharynx. Histopathologically, the tumour was partially organised, and the tumour cells were epithelioid or spindle-shaped. Initially, we erroneously diagnosed the tumour as an angiosarcoma owing to its false-negative immunoreaction for cytokeratins and a mistaken interpretation for CD31. After in situ hybridization for Epstein-Barr virus was positive, a consultation and additional immunostaining (including re-staining for cytokeratin with varying dilutions) were performed, and the diagnosis was revised to NK-SCC with sarcomatoid features. We believe that sarcomatoid features may be observed in nasopharyngeal carcinoma and in this case, immunostaining using various epithelial markers is necessary and careful attention should be paid to the interpretation of immunostaining.

Patterns of kidney injury in pediatric nonkidney solid organ transplant recipients.

The incidence of acute kidney injury (AKI) and its impact on chronic kidney disease (CKD) following pediatric nonkidney solid organ transplantation is unknown. We aimed to determine the incidence of AKI and CKD and examine their relationship among children who received a heart, lung, liver, or multiorgan transplant at the Hospital for Sick Children between 2002 and 2011. AKI was assessed in the first year posttransplant. Among 303 children, perioperative AKI (within the first week) occurred in 67% of children, and AKI after the first week occurred in 36%, with the highest incidence among lung and multiorgan recipients. Twenty-three children (8%) developed CKD after a median follow-up of 3.4 years. Less than 5 children developed end-stage renal disease, all within 65 days posttransplant. Those with 1 AKI episode by 3 months posttransplant had significantly greater risk for developing CKD after adjusting for age, sex, and estimated glomerular filtration rate at transplant (hazard ratio: 2.77, 95% confidence interval, 1.13-6.80, P trend = .008). AKI is common in the first year posttransplant and associated with significantly greater risk of developing CKD. Close monitoring for kidney disease may allow for earlier implementation of kidney-sparing strategies to decrease risk for progression to CKD.

Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.

Functional status of immune cells in patients with long-lasting type 2 diabetes mellitus.

Although patients with diabetes contract infectious diseases at higher frequencies, and in more severe forms, compared to non-diabetics, the underlying defects of the immune function have not been defined clearly. To address this, we designed an immune monitoring protocol and analysed the functional status of various immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with the proper ligands and the functional reactivity of each lineage of cells was subsequently measured. Patients with type 2 diabetes mellitus (T2DM) had PBMC composition ratios comparable to healthy controls, except for a higher frequency of B cell and effector T cell fractions. The capacity of myeloid cells to secrete proinflammatory cytokines was not diminished in terms of the sensitivity and magnitude of the response. Furthermore, cytolytic activity and interferon (IFN)-γ production of natural killer (NK) cells and CD8+ T cells were not decreased in T2DM patients. Phenotypical maturation of dendritic cells, indicated by the up-regulation of major histocompatibility complex (MHC) proteins and co-stimulatory molecules in response to lipopolysaccharide (LPS), was slightly enhanced in T2DM patients. Finally, the functional differentiation profiles of CD4+ T cells did not differ between T2DM patients and the control group. These data indicate that patients with long-lasting T2DM do not have any gross functional defects in immune cells, at least in circulating monocytes, dendritic cells, NK cells and T lymphocytes.