Multi-center validation of an artificial intelligence system for detection of COVID-19 on chest radiographs in symptomatic patients.

OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR. METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases. RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong's test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar's test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001). CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR. KEY POINTS: • An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. • Differences in AI model performance were seen across region, disease severity, gender, and age. • Prevalence simulations on the international test set demonstrate the model's NPV is greater than 98.5% at any prevalence below 4.5%.

Green tea extract as a cryoprotectant additive to preserve the motility and DNA integrity of human spermatozoa.

Cryopreservation impairs sperm quality and functions, including motility and DNA integrity. Antioxidant additives in sperm freezing media have previously brought improvements in postthawed sperm quality. Green tea extract (GTE) is widely considered as an excellent antioxidant, and its beneficial role has been proven in other human cells. This study aims to evaluate the GTE as a potential additive in cryopreservation media of human spermatozoa. In part one, the semen of 20 normozoospermic men was used to optimize the concentration of GTE that maintains sperm motility and DNA integrity against oxidative stress, induced by hydrogen peroxide (H2O2). Spermatozoa were treated with GTE at different concentrations before incubation with H2O2. In part two, the semen of 45 patients was cryopreserved with or without 1.0 ng ml-1 GTE. After 2 weeks, the semen was thawed, and the effect on sperm motility and DNA fragmentation was observed. Our data showed that GTE significantly protected sperm motility and DNA integrity against oxidative stress induced by H2O2when added at a final concentration of 1.0 ng ml-1. We found that the addition of 1.0 ng ml-1 GTE to cryopreservation media significantly increased sperm motility and DNA integrity (both P < 0.05). More interestingly, patients with high sperm DNA damage benefited similarly from the GTE supplementation. However, there was no significant change in the reactive oxygen species (ROS) level. In conclusion, supplementing sperm freezing media with GTE has a significant protective effect on human sperm motility and DNA integrity, which may be of clinical interest.

Cost of complex abdominal wall reconstruction with biological prostheses in a French public hospital.

GOAL: Retrospective analysis of bioprosthetic abdominal wall reconstruction in our center with regard to expenses and reimbursement. PATIENTS AND METHODS: This study included all patients undergoing bioprosthetic abdominal wall reconstruction between 2009 and 2015. All costs were considered in determining the hospital expenditures. Next we compared the incoming revenue for each hospital stay based on disease-related groups (DRG) and additional daily hospital fees. RESULTS: Seventy-six patients underwent abdominal wall reconstruction, 67 of whom had economical data that were exploitable. On the average, our center lost €15,233 for every hospital stay associated with bioprosthetic abdominal wall reconstruction. The existing DRG system is not well adapted to provide adequate reimbursement for costs related to complex abdominal wall repairs, especially when post-operative morbidity leads to prolonged hospital stay and increased expenses. CONCLUSION: Abdominal wall repairs with bioprostheses are expensive and are poorly reimbursed in the French Health care system, mainly because they are often associated with complications that increase the costs considerably. In our opinion, it seems necessary that either reimbursement of this type of prosthesis should be higher than the current DRG allows, or that the DRG classification be redefined, or even, that a specific DRG be created for complex abdominal wall reconstruction.

Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide-activated macrophages.

High mobility group box 1 (HMGB1) has been proposed as crucial in the pathogenesis of many diseases including sepsis. Acetylation of HMGB1 prevents its entry into the nucleus and leads to its secretion from the cell where it can trigger inflammation. We hypothesized that histone deacetylase 4 (HDAC4) controls the acetylation of HMGB1 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells via the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. The results showed that LPS treatment promoted the degradation of HDAC4 in a proteasome-dependent manner, which led to HMGB1 acetylation. In LPS-activated RAW264.7 cells, treatment with TAK-242 (a toll like receptor 4 inhibitor) and pyridone 6 (a JAK inhibitor) significantly inhibited HDAC4 degradation and acetylation of HMGB1, and thus prevented secretion of HMGB1. Decreased phosphorylation of STAT1 was also observed. Interestingly, HDAC4 overexpression significantly prevented the acetylation and secretion of HMGB1 in both RAW264.7 cells and isolated murine peritoneal macrophages. We conclude that HDAC4 might be a useful target for the treatment of sepsis.

Liquid culture enhances diagnosis of patients with milder forms of non-tuberculous mycobacterial lung disease.

OBJECTIVE: To evaluate the proportion and clinical characteristics of patients with non-tuberculous mycobacteria (NTM) lung disease diagnosed based on positive culture results in liquid medium only. METHODS: We reviewed the medical records of 978 patients diagnosed with NTM lung disease. All clinical samples were cultured in both solid and liquid media. RESULTS: Of the 978 patients, 111 (11.3%) were culture-positive in liquid medium only (liquid culture group), and 867 (88.7%) (solid culture group) on solid medium, regardless of the culture results in liquid medium. At the time of diagnosis, the liquid culture group was less likely than the solid culture group to have haemoptysis (11.7% vs. 20.0%, P = 0.04), positive sputum smear for acid-fast bacilli (14.4% vs. 50.2%, P < 0.001) or the fibrocavitary form of NTM lung disease (3.6% vs. 14.6%, P = 0.001). During the median follow-up period of 28.9 months (interquartile range 19.1-41.6), the proportion of patients requiring antibiotic treatment was lower in the liquid culture group than in the solid culture group (44.1% vs. 61.6%, P < 0.001). CONCLUSIONS: Liquid media culture is helpful in the diagnosis of patients with less severe forms of NTM lung disease.

Perirenal fat stranding on CT: is there an association with bladder outlet obstruction?

OBJECTIVE: To determine the association between perirenal fat stranding (PFS) on CT and bladder outlet obstruction (BOO). METHODS: CT scans from 122 patients who had undergone urodynamic study for lower urinary tract symptoms (LUTS) were registered after exclusion of patients with renal or retroperitoneal disease. Images were independently reviewed by two radiologists and compared with those of 244 age- and sex-matched control patients without LUTS. The PFS severity was scored on a four-point scale, and the interobserver agreement was assessed with kappa statistics. The severity score and incidence was compared between the groups, and the association with baseline characteristics was analyzed. For the LUTS group, an association between PFS severity and urodynamic and laboratory data was evaluated. RESULTS: PFS was more frequent and more severe in the LUTS group than in the control group (p-value < 0.001); its presence was significantly associated with male gender and older age (p-value < 0.001). PFS was predominantly bilateral in both groups (80.1-93.2%). In the LUTS group, PFS severity scores were significantly correlated with the maximum flow rate, maximum detrusor pressure and estimated glomerular filtration rate (p-value < 0.001). Interobserver agreements were excellent for PFS presence (κ = 0.883) and severity (κ = 0.816). CONCLUSION: Severe PFS was observed in older, male patients with LUTS. PFS severity was associated with the degree of BOO and impaired renal function. ADVANCES IN KNOWLEDGE: Recognition of PFS on the CT scan may warrant further evaluation of BOO and appropriate management to prevent renal impairment.

Effects of warm acupuncture on breast cancer-related chronic lymphedema: a randomized controlled trial.

BACKGROUND: Effective treatment for breast cancer-related chronic lymphedema (bcrl) remains a clinical challenge. Acupuncture and moxibustion treatments have been shown to be beneficial and safe for treating bcrl. In the present randomized controlled trial, we compared the effectiveness of combined acupuncture and moxibustion ("warm acupuncture") with that of diosmin in bcrl. METHODS: Breast cancer patients who met the inclusion and exclusion criteria (n = 30) were randomized to experimental and control groups (15 per group). On alternate days, patients in the experimental group received 30 minutes of acupuncture at 6 acupoints, with 3 of the needles each being topped by a 3-cm moxa stick. The control treatment was diosmin 900 mg 3 times daily. The control and experimental treatments were administered for 30 days. Outcome measures included arm circumferences (index of effectiveness), range of motion [rom (shoulder joint function)], quality of life, clinical safety, and adverse events. RESULTS: Measured by the index of effectiveness, bcrl improved by 51.46% in the experimental group and by 26.27% in the control group (p < 0.00001). Effects were greatest at 10 cm above the elbow and at the wrist, where the warm needling was provided. Impairments in shoulder joint rom were minimal at baseline in both treatment groups. However, the roms of rear protraction, abduction, intorsion, and extorsion in the experimental group improved significantly; they did not change in the control group. Self-reported quality of life was significantly better with warm acupuncture than with diosmin. No adverse effects were reported during the treatment period, and laboratory examinations for clinical safety fell within the normal ranges. CONCLUSIONS: Compared with diosmin, warm acupuncture treatment can effectively reduce the degree of bcrl at the specific acupoints treated and can promote quality of life. Warm acupuncture showed good clinical safety, without any adverse effects on blood or the cardiovascular system.

Epstein-Barr virus reactivation in extranodal natural killer/T-cell lymphoma patients: a previously unrecognized serious adverse event in a pilot study with romidepsin.

BACKGROUND: Romidepsin, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of relapsed and refractory peripheral T-cell lymphoma. However, the efficacy and safety of romidepsin has never been studied in patients with relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (ENKTL). PATIENTS AND METHODS: We conducted an open-label, prospective pilot study to evaluate the efficacy and feasibility of romidepsin in the treatment of patients with ENKTL. The treatment was intravenous infusion of romidepsin (14 mg/m(2)) for 4 h on days 1, 8, and 15 of a 28-day cycle, and was repeated until disease progression or the occurrence of unacceptable toxicity. RESULTS: A total of five patients enrolled on to this pilot study. However, three patients developed fever and elevated liver enzyme and bilirubin levels immediately after their first administration of romidepsin. We suspected that these events were associated with Epstein-Barr virus (EBV) reactivation because of the rapidly elevated EBV DNA titers in blood from these patients. An in vitro study with the ENKTL cell line SNK-6 cells also showed that HDAC inhibitors including romidepsin increased the copy number of EBV DNA in a dose-dependent manner. These findings suggested that romidepsin-induced histone acetylation reversed the repressed state of the genes required for EBV reactivation and that romidepsin treatment may have caused EBV reactivation in EBV-infected tumor cells in ENKTL patients. Therefore, we discontinued the enrollment of patients into this pilot study. CONCLUSIONS: Our study suggests that the use of romidepsin may cause severe EBV reactivation in patients with ENKTL.

Dual mode gelation behavior of silk fibroin microgel embedded poly(ethylene glycol) hydrogels.

Hydrogel formation by more than two cross-linking mechanisms is preferred for the sophisticated manipulation of hydrogel properties. Both chemical and physical crosslinks are often utilized for fabricating stimuli-responsive hydrogels or for compensating the drawbacks of the single crosslinking method. In this study, silk fibroin (SF) microgel embedded poly(ethylene glycol) (PEG) hydrogels were fabricated by dual mode cross-linking based on thiol-ene photo-click chemistry and ß-sheet formation of SF. Norbornene-functionalized SF (SF-NB) was incorporated into PEG hydrogels by photo-cross-linking. The equilibrium shear modulus of SF-PEG hybrid hydrogels decreased with increasing SF-NB content. However, the incorporation of SF-NB caused stiffening of SF-PEG hybrid hydrogels gradually over 5 days and the gel modulus was maintained for 2 weeks. In contrast, the modulus of pure PEG hydrogels decreased continuously owing to hydrolytic degradation of ester bonds in the PEGNB macromers. Structural analysis revealed that such a post-gelation stiffening effect was caused by ß-sheet transition in SF microgels embedded in the PEG hydrogel matrix. PEG hydrogels incorporated with 4 wt% SF microgels exhibited about 2-fold increase in shear modulus compared with the modulus on day 1 post-gelation. To evaluate the compatibility of these hydrogels as cell culture matrices, the cytotoxicity of the hydrogel was examined using in situ encapsulated A549 cells. SF-PEG hybrid hydrogels showed no apparent cytotoxicity and promoted the proliferation of encapsulated A549 cells even at a higher gel modulus compared with cells in pure PEG hydrogels. These results suggest that SF-PEG hybrid hydrogels fabricated by dual mode crosslinking serve as good candidates for three-dimensional cell culture requiring temporal control of hydrogel stiffness.

Solvatochromism and conformational changes in fully dissolved poly(3-alkylthiophene)s.

Absorption spectroscopy is commonly utilized to probe optical properties that can be related, among other things, to the conformation of single, isolated conjugated polymer chains in solution. It is frequently suggested that changes in peak positions of optical spectra result from variations in the stiffness of polymer chains in solution because this modifies the conjugation length. In this work we utilize ultraviolet-visible (UV-vis) spectroscopy, small angle neutron scattering (SANS), and all atom molecular dynamic (AA-MD) simulations to closely probe the relationship between the conformation of single-chains of poly(3-alkylthiophene)s (P3ATs) and their optical properties. SANS results show variations in the radius of gyration and Kuhn length as a function of alkyl chain length, and structure, as well as the solvent environment. Furthermore, both SANS and MD simulations show that dissolved P3HT chains are more rigid in solvents where self-assembly and crystallization are possible. Shifts in P3AT optical properties were also observed for different solvent environments. However, these changes were not correlated to the changes in polymer conformation. Furthermore, changes in optical properties could not be perfectly described by generalized solvent-solute interactions. AA-MD simulations provide new insights into specific polymer-solvent interactions not accounted for in generalized solvatochromic theory. This work highlights the need for experiments and molecular simulations that further inform the specific role of solvent molecules on local polymer conformation and on optical properties.

Effects of injection of acetic acid and propionic acid for total phosphorus removal at high temperature in enhanced biological phosphorus removal process.

In summer, wastewater treatment plant total phosphorus (TP) removal efficiency is low in South Korea. The reason is because of high temperatures or significant fluctuation of inflow characteristics caused by frequent rainfall. Hence, this study tried to raise TP removal efficiency by injecting fixed external carbon sources in real sewage. Polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs) compete to occupy microorganisms at high temperature. Propionate is known to restrain GAOs. Thus, acetate and propionate were chosen as the external carbon source in this study to find out the suitable volume and ratio of carbon source which ensured the dominance of PAOs. An external carbon source was supplied in the anaerobic reactor of the biological phosphorus removal process at high temperature (above 25 °C). TP removal efficiency was improved by injecting an external carbon source compared to that without an external carbon source. Also, it remained relatively stable when injecting an external carbon source, despite the variation in temperature. TP removal efficiency was the highest when injecting acetate and propionate in the proportion of 2:1 (total concentration as chemical oxygen demand (COD) is 12 mg/L in influent).

Frequency of FMR1 premutation carriers and rate of expansion to full mutation in a retrospective diagnostic FMR1 Korean sample.

Detection of female premutation (PM) carriers of fragile X syndrome may be important in that a PM allele from the mother can expand to a full mutation (FM) when transmitted to the fetus. Although the PM carrier frequency might be different in varying populations, there is a little data on the Korean population. Furthermore, the risks of expansion to FM have not been studied in Korean PM carriers. In this retrospective study, we estimated the female PM carrier frequency and the risks of expansion to FM in Korean diagnostic samples collected for FMR1 gene testing. Of 10,241 pre-conceptional or pregnant women, 13 PM [1 in 788; 95% confidence interval (CI), 1/1,250-1/455] and 75 intermediate allele carriers (1 in 137; 95% CI, 1/172-1/110) were identified. In 26 prenatal diagnoses cases, the PM allele was transmitted to the fetus in 13 pregnancies (50%), and five of these expanded to FM. All of the maternal alleles exceeding 70 repeats expanded to FM. In conclusion, the PM frequency in Korean diagnostic samples was lower than that reported in Western populations, while the risk for FM expansion in alleles exceeding 70 repeats might be higher than expected based upon previous reports.

Clinical characterization and molecular classification of 12 Korean patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism.

CONTEXT: Pseudohypoparathyroidism (PHP) is defined as resistance toward parathyroid hormones. PHP and pseudopseudohypoparathyroidism (PPHP) are rare disorders resulting from genetic and epigenetic aberrations within or upstream of the GNAS locus. This study investigated the clinical characteristics and performed a molecular analysis of PHP and PPHP. METHODS: A total of 12 patients with (P)PHP from 11 unrelated families (4 with PHP-Ia, 6 with PHP-Ib, and 2 with PPHP) were characterized using both clinical and molecular methods. Clinical features included the presenting symptoms, Albright hereditary osteodystrophy features, and resistance to hormones. Comprehensive analysis of the GNAS and STX16 loci was undertaken to investigate the molecular defects underlying (P)PHP. RESULTS: All PHP-Ib patients displayed hypocalcemic symptoms. All PHP-Ia patients showed resistance toward TSH, in addition to PTH. In most patients with PHP, when the diagnosis of PHP was first established, hypocalcemia and hyperphosphatemia were associated with a significant increase in serum PTH levels. One patient with PHP-Ia was diagnosed with growth hormone deficiency and showed a good response to human recombinant growth hormone therapy. 6 patients with PHP-Ia and PPHP showed 5 different mutations in the GNAS gene. 5 patients with PHP-Ib displayed a loss of differentially methylated region (DMR) imprints of the maternal GNAS. One PHP-Ib patient showed a de novo microdeletion in STX16 and a loss of methylation of exon A/B on the maternal allele. No patients revealed paternal disomy among 4 patients with PHP-Ib. CONCLUSIONS: Identification of the molecular causes of PHP and PPHP explains their distinctive clinical features and enables confirmation of the diagnosis and exact genetic counseling.

Effect of belly board with bladder compression device on small bowel displacement from the radiotherapy field for rectal cancer.

BACKGROUND: The aim of this study was to investigate the effect of a belly board (BB) with the addition of a bladder compression device (BCD) for small bowel (SB) displacement from the radiotherapy field for rectal cancer. PATIENTS AND METHODS: Computed tomography (CT) scans of 38 rectal cancer patients positioned on a BB were analyzed and compared with CT scans from the same patients after the addition of a BCD. The BCD moves the inferior border of the BB from the pubic symphysis to the lumbosacral junction. The treated and irradiated volumes of the SB and bladder were compared. The irradiated volume ratio of SB to abdominopelvic cavity (APC) and that of bladder to APC were analyzed. RESULTS: With the BCD, the treated and irradiated volumes of SB decreased significantly (49.1 ± 48.0 vs. 60.9 ± 50.9 cc, p = 0.006 and 207.5 ± 140.8 vs. 482.8 ± 214.2 cc, p < 0.001, respectively). The irradiated volume ratio of bladder to APC with the BCD increased considerably compared to that without the BCD (25.2 ± 11.5 vs. 18.7 ± 10.5%, p < 0.001), and the ratio of irradiated volume of SB to APC decreased significantly with the BCD (18.8 ± 12.4 vs. 31.8 ± 12.1%, p < 0.001). CONCLUSION: This study showed that the addition of a BCD to the BB could effectively provide further displacement of SB from the rectal cancer radiotherapy field.

Bleeding outcomes after routine transradial primary angioplasty for acute myocardial infarction using eptifibatide and unfractionated heparin: a single-center experience following the HORIZONS-AMI trial.

OBJECTIVES: We sought to (1) determine the bleeding rates after primary percutaneous coronary intervention (PPCI) in our institution, where the default strategy has been transradial (TR) access in combination with unfractionated heparin (UFH) plus eptifibatide, and (2) compare these with the outcomes of patients treated with bivalirudin in HORIZONS-AMI. BACKGROUND: HORIZONS-AMI demonstrated that in PPCI undertaken via the transfemoral route, routine use of bivalirudin was associated with lower bleeding rates and improved mortality compared to routine use of UFH plus glycoprotein IIb/IIIa inhibitor (GPI). METHODS: This was a single-center prospective registry of consecutive patients undergoing PPCI from January 2009 to August 2011 at the Queen Elizabeth Hospital Birmingham, UK. Thirty-day major bleeding was defined as per the HORIZONS-AMI criteria and also according to TIMI and GUSTO scales. RESULTS: Of the 432 consecutive patients, 350 fulfilled entry criteria for HORIZONS-AMI. In contrast with HORIZONS-AMI, these subjects were older (62.5 ± 13.7 yr vs. 59.8 ± 11.1 yr, P < 0.05) with a higher rate of cardiogenic shock (6.3% vs. 0.8%, P < 0.0001). Despite this higher risk population, the rate of major bleeding was favorable (3.7% [95% CI: 2.0-6.3%] vs. 4.9% [4.0-6.1%], P = 0.32). Similarly, TIMI major bleeding (2.0% [0.8-4.1%] vs. 3.1% [2.3-3.4%], P = 0.10) and GUSTO severe or life-threatening bleeding (0.6% [0.1-2.5%] vs. 0.4% [0.2-0.9%], P = 0.75) were comparable. CONCLUSIONS: Routine TR access for PPCI using UFH plus GPI is associated with a low 30-day rate of major bleeding equivalent to the bivalirudin arm of HORIZONS-AMI. Default transradial access for PPCI permits routine use of a GPI without the penalty of high bleeding rates.