Added value of non-contrast CT for the diagnosis of acute pyelonephritis in older patients with suspected infection with an unknown focus: a retrospective diagnostic study.

OBJECTIVES: In older patients, the diagnosis of acute pyelonephritis (APN) is challenging. The aim was to evaluate the added value of CT to history, physical examination and urinalysis for the diagnosis of APN in older patients with suspected infection with an unknown focus. DESIGN: Retrospective diagnostic study. SETTING: Department of General Medicine in an acute care hospital in Japan. PARTICIPANTS: Patients aged ≥65 years who underwent blood cultures, a urine culture, and chest and abdominal CT to detect the focus of infection were included. PRIMARY OUTCOME MEASURES: Two radiologists independently reviewed four non-contrast CT signs: perirenal fat stranding, pelvicalyceal wall thickening, enlargement of the kidney and thickening of Gerota's fascia. Findings on contrast-enhanced CT could not be evaluated due to an insufficient number of patients in whom contrast-enhanced CT was performed. An expert panel was used as the reference standard for APN. The added value of CT findings was quantified by comparing the diagnostic performance between a model based on 10 predictors available before CT and an extended model including the CT findings. RESULTS: Of 473 patients, 61 (14.8%) were diagnosed with APN. When the laterality of the CT findings was taken into account, the model fit was not improved by adding them. In the laterality-insensitive analysis, the model performance was significantly improved by adding the CT signs (likelihood-ratio test p=0.03; c-index 0.89 vs 0.91, p=0.03). However, their clinical utility was only to improve the classification of 11.5% of patients with APN. CONCLUSIONS: The added value of non-contrast CT findings to history, physical examination and urinalysis was limited for the diagnosis of APN in older patients with a suspected infection with an unknown focus.

Usefulness of computed tomography in the diagnosis of acute pyelonephritis in older patients suspected of infection with unknown focus.

BACKGROUND: In older adults, the diagnosis of acute pyelonephritis is challenging because of non-specific symptoms and false-positive urine test results. Few studies have investigated the diagnostic performance of computed tomography (CT) signs. PURPOSE: To evaluate the diagnostic performance of CT signs for acute pyelonephritis in older patients suspected of infection with unknown focus. MATERIAL AND METHODS: This cross-sectional study was conducted between 2015 and 2018. Patients aged ≥65 years who underwent blood cultures, urine culture, and non-contrast or contrast-enhanced CT on admission were included. Cases with clinically presumable infection focus before CT were excluded. Two radiologists blinded to clinical information independently reviewed five CT signs: perirenal fat stranding; pelvicalyceal wall thickening and enhancement; renal enlargement; thickening of Gerota's fascia; and area(s) of decreased attenuation. The final diagnoses were made by a clinical expert panel. RESULTS: Among 473 eligible patients, 61 were diagnosed with acute pyelonephritis. When the laterality of findings between the left and right kidneys were considered, the positive and negative likelihood ratios of perirenal fat stranding were 4.0 (95% confidence interval [CI] = 2.3-7.0) and 0.8 (95% CI = 0.7-0.9) in non-contrast CT, respectively. The other signs in non-contrast CT showed similar diagnostic performance with positive and negative likelihood ratios of 3.5-11.3 and 0.8-0.9, respectively. CONCLUSION: CT signs can help physicians diagnose acute pyelonephritis in older patients suspected of infection with unknown focus.

Synthetic microbial consortium with specific roles designated by genetic circuits for cooperative chemical production.

Synthetic microbial consortia consisting of microorganisms with different synthetic genetic circuits or divided synthetic metabolic pathway components can exert functions that are beyond the capacities of single microorganisms. However, few consortia of microorganisms with different synthetic genetic circuits have been developed. We designed and constructed a synthetic microbial consortium composed of an enzyme-producing strain and a target chemical-producing strain using Escherichia coli for chemical production with efficient saccharification. The enzyme-producing strain harbored a synthetic genetic circuit to produce beta-glucosidase, which converts cellobiose to glucose, destroys itself via the lytic genes, and release the enzyme when the desired cell density is reached. The target chemical-producing strain was programmed by a synthetic genetic circuit to express enzymes in the synthetic metabolic pathway for isopropanol production when the enzyme-producing strain grows until release of the enzyme. Our results demonstrate the benefits of synthetic microbial consortia with distributed tasks for effective chemical production from biomass.

One-year results of voluntary-based supervised exercise or treatment at orthopedic clinic for radiographic severe knee osteoarthritis.

[Purpose] In this study, we investigated the efficacy of supervised physical exercise or conventional treatment on symptomatic knee osteoarthritis with severe morphological degeneration. [Subjects] Sixty-six patients with severe radiographic knee osteoarthritis were enrolled. [Methods] Participants were separated into two groups: in one group patients conducted physical exercise under supervision; while in the other group they were treated by conventional clinical methods for one year. Participants filled out two types of questionnaires; the Japanese Knee Osteoarthritis Measure and the Pain Disability Assessment Scale at baseline and one year following enrollment in the study. Two-way repeated measures analysis of variance was used to examine the effects over time and by group for a total of 43 participants; consisting of an exercise group (n=20) and a clinical group (n=23) excluding 23 dropouts. [Results] Analysis did not show a significant time-course effect or interaction between time-course and the groups in both questionnaires. On the other hand, there were significant group effects in both questionnaires with an advantage in the exercise group. [Conclusion] These results indicate that patients with knee osteoarthritis under supervised exercise conditions are more likely to maintain a better clinical outcome at one-year follow-up, despite the severe morphological degeneration in their knees.

Enhancement of 3-hydroxypropionic acid production from glycerol by using a metabolic toggle switch.

BACKGROUND: 3-hydroxypropionic acid (3-HP) is an important platform for the production of C3 chemicals, including acrylic acid, methyl acrylate, and acrylamide. Microbial production of 3-HP is mainly due to glycerol metabolism. In this study, in order to improve microbial 3-HP production, we applied a metabolic toggle switch for controlling the glycerol metabolism to redirect the excess metabolic flux of central metabolic pathway toward an exogenous 3-HP producing pathway in Escherichia coli. RESULTS: The metabolic toggle switch enables conditional repression of the expression of a target gene during the fermentation. We individually performed conditional repression of glpK, tpiA, and gapA, which are involved in glycerol metabolism. The conditional repression of glpK and tpiA was not effective for 3-HP production under our experimental conditions. However, gapA conditional repression contributed to improve 3-HP production (titer, 54.2 ± 1.5 mM; yield, 32.1 ± 1.3 %) compared with that for the wild type strain. Additional deletion of endogenous yqhD, which is responsible for the production of a major byproduct, 1,3-propandiol, further increased 3-HP production (titer, 67.3 ± 2.1 mM; yield, 51.5 ± 3.2 %). The titer and yield were 80 and 94 % higher than those of the wild type strain, respectively. The obtained 3-HP yield from glycerol is comparable with the highest yield ever reported for microbial 3-HP production using glycerol as a sole carbon source. The measurement of intracellular metabolites showed the metabolic toggle switch successfully controlled the metabolic flux. CONCLUSION: The conditional repression of gapA by using the metabolic toggle switch combined with deletion of endogeneous yqhD increased 3-HP production approximately twofold from glycerol. This result indicates the metabolic toggle switch can be applied in various bio-production using diverse substrates.

Dual synthetic pathway for 3-hydroxypropionic acid production in engineered Escherichia coli.

3-Hydroxypropionic acid (3-HP) is an important platform C3 chemical; production of 3-HP in recombinant Escherichia coli by synthetic pathways has been the focus of a lot of research. When glycerol is used as a substrate to produce 3-HP in E. coli, only the ALDH pathway (employing aldehyde dehydrogenase (ALDH) for conversion of 3-hydroxypropionaldehyde (3-HPA) into 3-HP) has been utilized as a synthetic pathway. However, several bacteria (including Klebsiella pneumoniae) are known to have the ability to produce 3-HP by the Pdu pathway (employing the PduP, PduL, and PduW enzymes). Here, we report the production of 3-HP in E. coli by using the Pdu pathway from K. pneumoniae as a synthetic pathway. Moreover, a strain harboring a dual synthetic pathways (ALDH and Pdu) exhibited a 70% increase in 3-HP titer compared to one harboring the ALDH pathway alone (56.1 ± 0.736 mM and 33.1 ± 0.920 mM, respectively). To our knowledge, this is the first report of 3-HP production by E. coli harboring the Pdu pathway, with the dual synthetic pathway showing the highest yield ever reported by batch culture [54.1% (mol/mol)].

A phase II study of radiofrequency ablation therapy for thoracic malignancies with evaluation by FDG-PET.

PURPOSE: Computed tomography (CT)-guided radiofrequency ablation (RFA) is safe and effective for patients with unresectable primary, recurrent, or metastatic thoracic malignancies. Several studies have shown the benefit of employing 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET) to follow thoracic malignancies treated with RFA. In this prospective study, we show the safety and therapeutic efficacy of RFA and the utility of FDG-PET as tool for early detection of local recurrence. METHODS: Twenty patients were enrolled in this study, and 24 lesions were ablated. Seven lesions were primary lung cancer, and 17 lesions were recurrent tumors or metastases from extrathoracic sites. Tumor size was in the range of 0.4-3.3 cm in diameter (mean: 1.5 cm). CT and FDG-PET scans were scheduled 7-14 days and 3-6 months after RFA treatment. RESULTS: There were 17 adverse events (70.8 %) in 24 ablations included 13 pneumothoraces, two cases of chest pain, and two episodes of fever. With a median follow-up of 35.9 months (range 1-62 months), the overall 2-year survival rate was 84.2 %. Local recurrence occurred at four sites (2-year local control rate was 74.3 %). The FDG-PET results 7-14 days after RFA did not predict recurrence, whereas positive findings 3-6 months after RFA significantly correlated with local recurrence (p = 0.0016). CONCLUSIONS: We confirmed the effectiveness of RFA for unresectable primary and secondary thoracic malignancies. FDG-PET analysis 3-6 months after ablation is a useful tool to assess local control.