Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery.

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml-1 or < 300 ng.ml-1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127-141 [120-172]) g.l-1 , 143 (133-150 [120-179]) g.l-1 , p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77-82 [9-85]) days vs. 81 (79-83 [0-85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion.

Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer.

BACKGROUND: This international, randomized, double-blind phase III study (ONO-4538-52/TASUKI-52) evaluated nivolumab with bevacizumab and cytotoxic chemotherapy as first-line treatment for nonsquamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between June 2017 and July 2019, this study enrolled treatment-naïve patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. They were randomly assigned in a 1 : 1 ratio to receive nivolumab or placebo in combination with carboplatin, paclitaxel, and bevacizumab every 3 weeks for up to six cycles, followed by nivolumab/placebo with bevacizumab until progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by an independent radiology review committee (IRRC). RESULTS: Overall, 550 patients from Japan, Korea, and Taiwan were randomized; of these patients, 273 and 275 received the nivolumab and placebo combinations, respectively. In the present preplanned interim analysis with a median follow up of 13.7 months, the IRRC-assessed median PFS was significantly longer in the nivolumab arm than in the placebo arm (12.1 versus 8.1 months; hazard ratio 0.56; 96.4% confidence interval 0.43-0.71; P < 0.0001). The PFS benefit was observed across all patients with any programmed death-ligand 1 (PD-L1) expression levels including PD-L1-negative patients. The IRRC-assessed objective response rates were 61.5% and 50.5% in the nivolumab and placebo arms, respectively. The incidence of treatment-related adverse events of grade 3 or 4 was comparable between the two arms; treatment-related adverse events leading to death were observed in five and four patients in the nivolumab and placebo arms, respectively. CONCLUSION: The TASUKI-52 regimen should be considered a viable new treatment strategy for treatment-naïve patients with advanced nonsquamous NSCLC.

Antifungal and anti-biofilm effects of 6-shogaol against Candida auris.

AIMS: This study aimed to assess the antifungal and anti-biofilm effects of 6-shogaol against Candida auris using in vitro phenotypic and genotypic analyses. METHODS AND RESULTS: Our results showed that 6-shogaol exhibited antifungal as well as anti-biofilm activity by inhibiting biofilm formation and eradicating the preformed biofilms of C. auris. The rate and extent of antifungal activity were further confirmed by a time-kill assay. The XTT reduction assay confirmed that 6-shogaol decreased cellular metabolic activity in the biofilm. The effect of 6-shogaol on established C. auris biofilms was visualized by confocal laser scanning microscopy. Also, this study demonstrated that 6-shogaol reduced the levels of aspartyl proteinases and downregulated the expression of the efflux pump-related CDR1 gene in C. auris. CONCLUSIONS: The data indicated that 6-shogaol extracted from ginger had antifungal and anti-biofilm effects on C. auris. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the value of the plant-derived 6-shogaol as a promising and potent bioactive compound. The mode of action of this compound against C. auris biofilm was also proposed.

Comparative outcomes of robot-assisted minimally invasive versus open esophagectomy in patients with esophageal squamous cell carcinoma: a propensity score-weighted analysis.

Robots are increasingly used in minimally invasive surgery. We evaluated the clinical benefits of robot-assisted minimally invasive esophagectomy (RAMIE) in comparison with the conventional open esophageal surgery. From 2012 to 2016, 371 patients with esophageal squamous cell carcinoma underwent an Ivor Lewis or McKeown procedure at our institution. Of these, 130 patients underwent laparoscopic gastric conduit formation followed by RAMIE, whereas 241 patients underwent conventional esophageal surgery, including laparotomy and open esophagectomy (OE). We compared the short- and long-term clinical outcomes of these patients using the propensity score-based inverse probability of treatment weighting technique (IPTW). Among the early outcomes, the OE group showed a higher incidence of pneumonia (P = 0.035) and a higher requirement for vasopressors (P = 0.001). Regarding the long-term outcomes, all-cause mortality was significantly higher (P = 0.001) and disease-free survival was lower (P = 0.006) in the OE group. Wound-related problems also occurred more frequently in the OE group (P = 0.020) during the long-term follow-up. There was no statistical intergroup difference in the recurrence rates (P = 0.191). The Cox proportional-hazard analysis demonstrated that wound problems (HR 0.16, 95% CI 0.02-0.57; P = 0.017), pneumonia (HR 0.23, 95% CI 0.06-0.68; P = 0.019), and use of vasopressors (HR 0.14, 95% CI 0.08-0.25; P = 0.001) were independent predictors of mortality. RAMIE could be a better surgical option for selected patients with esophageal squamous cell carcinoma.

A new aortoiliac calcification scoring system to predict grade C anastomotic leak following rectal cancer surgery.

BACKGROUND: Aortoiliac calcification may be a surrogate marker of decreased visceral perfusion causing anastomotic leak (AL). The aim of this study was to evaluate the predictive role of aortoiliac calcification for AL after rectal cancer surgery. METHODS: We enrolled patients with primary rectal cancer who had restorative resection at our institution between January 2013 and December 2015. An aortoiliac calcification score was calculated as the sum of calcification scores at the infrarenal aorta (0: no, 1: ≤ 3 cm, 2: > 3 cm) and the common iliac arteries (0: no, 1: unilateral, 2: bilateral). AL was classified into three grades: grade A, requiring no intervention; grade B, requiring therapeutic intervention without re-laparotomy; and grade C, requiring re-laparotomy. Clinicopathological characteristics were analyzed to identify risk factors for AL. RESULTS: There were 583 patients. Three-hundred forty-five (59.2%) had an aortoiliac calcification score ≥ 3, and 37 (6.3%) patients experienced AL, in 30 cases (5.1%) grade C AL. Patients with an aortoiliac calcification score ≥ 3 had a higher incidence of grade C AL (6.7% vs. 2.9%, p = 0.045). Multivariate logistic regression analysis revealed that an aortoiliac calcification score ≥ 3 was an independent risk factor for grade C AL (odds ratio = 2.669, 95% confidence interval 1.066-6.686, p = 0.036). CONCLUSIONS: Aortoiliac calcification may be considered a risk factor for grade C AL after rectal cancer surgery.

The effects of short-chain fatty acids on the transcription and secretion of apolipoprotein A-I in human hepatocytes in vitro.

BACKGROUND: Apolipoprotein-I (ApoA-I), the major component of high-density lipoprotein (HDL) particles, mediates cholesterol efflux by which it facilitates the removal of excess cholesterol from peripheral tissues. Therefore, elevating ApoA-I production leading to the production of new pre-ß-HDL particles is thought to be beneficial in the prevention of cardiovascular diseases. Recently, we observed that amoxicillin treatment led to decreased HDL concentrations in healthy human volunteers. We questioned whether this antibiotic effect was directly or indirectly, via changed short-chain fatty acids (SCFA) concentrations through an altered gut microflora. Therefore, we here evaluated the effects of amoxicillin and various SCFA on hepatic ApoA-I expression, secretion, and the putative underlying pathways. METHODS AND RESULTS: Human hepatocytes (HepG2) were exposed to increasing dose of amoxicillin or SCFA for 48 hours. ApoA-I messenger RNA (mRNA) transcription and secreted protein were analyzed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. To study underlying mechanisms, changes in mRNA expression of KEAP1, CPT1, and PPARα, as well as a PPARα transactivation assay, were analyzed. Amoxicillin dose-dependently decreased ApoA-I mRNA transcription as well as ApoA-I protein secretion. SCFA treatment resulted in a dose-dependent stimulation of ApoA-I mRNA transcription, however, the ApoA-I protein secretion was decreased. Furthermore, SCFA treatment increased PPARα transactivation, PPARα and CPT1 mRNA transcription, whereas KEAP1 mRNA transcription was decreased. CONCLUSION: Direct treatment of HepG2 cells with amoxicillin has either direct effects on lowering ApoA-I transcription and secretion or indirect effects via modified SCFA concentrations because SCFA were found to stimulate hepatic ApoA-I expression. Furthermore, BET inhibition and PPARα activation were identified as possible mechanisms behind the observed effects on ApoA-I transcription.

Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer.

BACKGROUND: Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade. PATIENTS AND METHODS: We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD. RESULTS: A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival [hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868-7.440] and overall survival (HR, 5.079; 95% CI, 3.136-8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7-CD45RA- T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate. CONCLUSION: HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.

Diagnostic value of ultrasound in calcium pyrophosphate deposition disease of the knee joint.

OBJECTIVE: To assess the diagnostic performance of ultrasound (US) for calcium pyrophosphate deposition (CPPD) at the level of menisci, hyaline cartilage (HC), tendons, and synovial fluid (SF) of the knee, and to examine inter- and intra-observer reliability. DESIGN: We consecutively included patients with knee effusion over a 2-year period (43 patients with CPPD and 131 controls). All patients underwent SF analysis, conventional radiography (CR), and US examination using the Outcome Measures in Rheumatology (OMERACT) definition of the US characteristics of CPPD. Two independent operators performed the US, and inter-observer agreement was calculated. Intra-observer agreement was examined with static images obtained for all enrolled patients. RESULTS: US revealed calcium pyrophosphate (CPP) deposits in menisci, HC, and tendon more frequently in patients with CPPD than in control patients. The presence of US CPP deposits in SF was not significantly different between the two groups. Combined US evaluation of the three components (menisci, HC, and tendon) showed the best diagnostic performance. The sensitivity and specificity for US evaluation of the three components were 74.4% and 77.1%, respectively, while for CR evaluation, the sensitivity and specificity were 44.2% and 96.9%, respectively. Inter- and intra-observer agreement were excellent for medial (κ = 0.930, 0.972) and lateral menisci (κ = 0.905, 0.942), HC (κ = 0.844, 0.957), and SF (κ = 0.817, 0.925). Tendon showed fair inter-observer (κ = 0.532) and good intra-observer reliability (κ = 0.788). CONCLUSIONS: Based on the OMERACT definition, US demonstrated better diagnostic capacity than CR to diagnose CPPD, with excellent reliability. Combined evaluation of menisci, HC, and tendon showed the best diagnostic accuracy.

Amoxicillin Modulates ApoA-I Transcription and Secretion, Predominantly via PPARα Transactivation Inhibition.

In a recent human study, we observed that amoxicillin treatment decreased HDL-C concentration. We hypothesize that antibiotics lower the transcription and secretion of ApoA-I, the responsible protein for HDL production. HepG2 and Caco-2 cells were exposed to increasing dose of amoxicillin, penicillin, and streptomycin. Secreted ApoA-I protein and mRNA transcripts were analyzed using ELISA and qPCR, respectively. To unravel underlying mechanisms, KEAP1, CPT1, and CHOP mRNA expressions were determined as well as PPARα transactivation. In HepG2 and Caco-2, amoxicillin decreased ApoA-I transcription and secretion. Effects on ApoA-I expression were clearly there for amoxicillin while no effects were observed for penicillin or streptomycin. KEAP1, CPT1, and CHOP mRNA expressions were reduced by amoxicillin treatments. Moreover, a significant correlation between ApoA-I and CPT1 mRNA expressions was found. Furthermore, amoxicillin lowered PPARα transactivation. All together, these data suggest that inhibited PPARα transactivation is involved in the effects of amoxicillin on ApoA-I. In conclusion, the direct effect of amoxicillin in treated HepG2 and Caco-2 cells was a lower ApoA-I secretion and transcription. Based on evaluating alterations in KEAP1, CPT1, and CHOP mRNA expressions plus PPARα transactivation, we suggest that a reduced PPARα activation is a potential mechanism behind the observed amoxicillin effects on ApoA-I expression.

Allergen-specific immunotherapy induces regulatory T cells in an atopic dermatitis mouse model.

BACKGROUND: Several studies have demonstrated that allergen-specific immunotherapy (SIT) can be an effective treatment for atopic dermatitis (AD). However, there is no relevant mouse model to investigate the mechanism and validate the novel modality of SIT in AD. METHODS: NC/Nga mice with induced AD-like skin lesions received a subcutaneous injection of SIT (an extract of the house dust mite Dermatophagoides farinae [DfE]) or placebo for 5 weeks). Clinical and histological improvements of AD-like skin lesions were examined. The responses of local and systemic regulatory T (Treg) cells, natural killer (NK) cells, B cells, serum immunoglobulin, and T-cell cytokine response to DfE were evaluated to determine the underlying mechanism of the observed results. RESULTS: Specific immunotherapy significantly improved AD-like skin lesions. Histologically, SIT decreased epidermal thickness and reduced inflammatory cell infiltration, especially that of eosinophils. Concomitantly, SIT suppressed Th2 responses and induced local infiltration of Treg cells into the skin. Also, SIT induced the immunoglobulin G4 and attenuated allergen-specific immunoglobulin E. Furthermore, SIT induced local and systemic IL-10-producing Treg cells and regulatory NK cells. CONCLUSION: We established a SIT model on AD mice and showed that our model correlates well with previous reports about SIT-treated patients. Also, we revealed NK cells as another possible resource of IL-10 in SIT. Based on our results, we suggest our SIT model as a useful tool to investigate mechanism of action of SIT and to validate the efficacy of new SIT modalities for the treatment of AD.

Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma.

BACKGROUND: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). METHODS: The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling. RESULTS: The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations of FGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib. CONCLUSIONS: FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.

Identification of the biosynthesis gene cluster for the novel lantibiotic paenilan from Paenibacillus polymyxa E681 and characterization of its product.

AIMS: To analyse the function of a putative lantibiotic gene cluster of Paenibacillus polymyxa E681 and to characterize its product, paenilan. METHODS AND RESULTS: Comparative analysis of the lantibiotic gene cluster of E681 revealed that the cluster, consisting of 11 open reading frames, is involved in the biosynthesis of a class I lantibiotic. The pnlA gene encoding the prepeptide PnlA was identified and P. polymyxa strain EPT14 producing only paenilan was constructed by knockout of the other five antibiotic biosynthetic gene clusters of E681. Paenilan was purified from EPT14 culture by solvent partitioning, ODS silica gel chromatography and reversed-phase preparative HPLC. The molecular mass (2510·10 Da) and structure of paenilan analysed by Nanoelectrospray ionization mass spectrometry (MS) and MS/MS showed that paenilan is a novel class I lantibiotic. Paenilan exhibited antimicrobial activity against Gram-positive bacteria such as Bacillus cereus, Micrococcus luteus and Paenibacillus durus. The paenilan gene is well-conserved in different Paenibacillus sp. isolated from globally distant places. CONCLUSIONS: The lantibiotic gene cluster of P. polymyxa E681 was analysed and its product, a novel and useful lantibiotic named paenilan that inhibits the growth of some Gram-positive bacteria, was characterized. SIGNIFICANCE AND IMPACT OF THE STUDY: Paenibacillus species are a good source of new lantibiotics, and the conservation of the paenilan gene among Paenibacillus sp. implies paenilan has an important function(s) for their survival.

Prognostic impact of the length of the longitudinal resection margin in colon cancer.

AIM: Although several guidelines recommend a longitudinal resection margin (LRM) of at least 5 cm, the impact of the LRM on survival is still unknown. The study assessed the prognostic significance of the LRM in patients with colon cancer. METHOD: We retrospectively reviewed 1343 primary colon cancer patients without distant metastasis who underwent curative resection between January 2004 and December 2012. Patients were classified into three groups: LRM < 3 cm (n = 186), LRM ≥ 3 and <5 cm (n = 376) and LRM ≥5 cm (n = 781). Clinicopathological characteristics and the oncological outcome in the three groups were compared. RESULTS: The median LRM length was 5.0 cm (range 0.5-26.0 cm). With increasing LRM, the number of retrieved lymph nodes (LNs) tended to increase (19.5 ± 12.0, 22.1 ± 12.8 and 30.0 ± 16.2; P < 0.001). After a median follow-up period of 45 (1-128) months, 3-year disease-free survival (DFS) (89.2%, 89.0% and 87.0%; P = 0.629) and 5-year overall survival (OS) (89.0%, 92.1% and 91.8%; P = 0.679) were not significantly different between the three groups. When confounders were adjusted, LRM was not significantly associated with either DFS or OS, but the number of retrieved LNs (< 12) was an independent risk factor for both DFS (hazard ratio 1.748, 95% confidence interval 1.048-2.917) and OS (hazard ratio 1.929, 95% confidence interval 1.046-3.559). CONCLUSION: LRM was not associated with oncological outcome, but care should be taken to obtain an adequate number of LNs for better survival.

Estimating the Basal metabolic rate from fat free mass in individuals with motor complete spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: This study aimed to validate the existing basal metabolic rate (BMR) predictive equations that include fat free mass (FFM) as an independent variable and, based on the FFM assessment, to develop a new SCI population-specific equation. SETTING: Outpatient clinic in a general hospital. METHODS: Our study group was formed of 50 individuals with chronic motor complete SCI: 27 patients with tetraplegia and 23 with paraplegia. Both BMR and FFM values were measured by indirect calorimetry (IC) and the whole-body dual energy X-ray absorptiometry, respectively. The BMR values measured by IC were compared with the values estimated from the Cunningham equation. Multiple linear regression analysis was performed to develop a new FFM-based, BMR predictive equation. RESULTS: The mean value of BMR measured by IC was 1274.8 (s.d.=235.2) kcal day-1. The intra-class correlation coefficient (ICC) between values measured by IC and estimated from the Cunningham equation was 0.845 and the limits of agreement ranged from -30.6 to 241.3 kcal. SCI population specific BMR predictive equation was developed; BMR (kcal day-1)=24.5 × FFM (kg)+244.4. The newly developed equation showed ICC of 0.866 with the limits of agreement from -229.0 to 233.1 kcal day-1. CONCLUSIONS: A considerable bias from the BMR values measured by IC was still observed, which warrants clinical consideration when applying FFM-based BMR prediction equations to individuals with SCI.

Severe spasticity in lower extremities is associated with reduced adiposity and lower fasting plasma glucose level in persons with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To investigate the effects of severe lower extremity spasticity on anthropometric dimensions, body composition and metabolic profiles in persons with chronic motor complete spinal cord injury (SCI). SETTING: Outpatient clinic. METHODS: Fifty-five of the 61 participants were divided into two groups (no or mild spasticity group, 28; severe spasticity group, 27) based on the assessment of the extensor muscle spasticity according to the modified Ashworth scale. Anthropometric dimensions (waist circumference (WC), waist-to-height ratio (WtHR)), body composition (fat mass (FM), body fat percentage (BFP), fat-free mass (FFM), fat-free mass percentage (FFMP), bone mineral density (BMD)) and metabolic profiles (leptin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c)) were compared between the two groups with different degree of spasticity. RESULTS: Spasticity of the extensor muscle group negatively correlated with BFP (r=-0.458, P<0.001). Patients with severe spasticity showed a lower WC and WtHR than those in the no or mild spasticity group (P=0.038, P=0.006, respectively). The FM, BFP, leptin and FPG of the severe spasticity group were significantly lower than those of the patients in the no or mild spasticity group (P=0.003, P<0.001, P<0.001 and P=0.037, respectively). However, no differences in BMD, total cholesterol, LDL, HDL, TG and HbA1c were observed between the groups. CONCLUSIONS: The results of this study suggest that severe spasticity in lower extremities is associated with reduced adiposity and lower FPG levels in persons with chronic motor complete SCI.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

Computed tomography findings associated with bacteremia in adult patients with a urinary tract infection.

The use of computed tomography (CT) in the diagnosis of urinary tract infection (UTI) has rapidly increased recently at acute stage, but the CT findings associated with bacteremia in UTI patients are unknown. 189 UTI patients were enrolled who underwent a CT scan within 24 h after hospital admission. We classified CT findings into eight types: a focal or multifocal wedge-shaped area of hypoperfusion, enlarged kidneys, perinephric fat stranding, ureteritis or pyelitis, complicated renal cyst, renal papillary necrosis, hydronephrosis, and renal and perirenal abscess. A retrospective analysis was conducted to evaluate the CT findings associated with bacteremia. The mean age of these patients was 60 ± 17.2 years, and 93.1 % were women. Concurrent bacteremia was noted in 40.2 % of the patients. Abnormal CT findings were noted in 96.3 % of the patients and 62.4 % had two or more abnormal findings. The most frequent abnormal CT finding was a focal or multifocal wedge-shaped area of hypoperfusion (77.2 %), followed by perinephric fat stranding (29.1 %). Perinephric fat stranding, hydronephrosis, and the presence of two or more abnormal CT findings were significantly associated with bacteremia in patients with community-acquired UTI. In the multivariate logistic regression analysis, age [odds ratio (OR) 1.03; 95 % confidence interval (CI) 1.009-1.062], two or more abnormal CT findings (OR 3.163; 95 % CI 1.334-7.498), and hydronephrosis (OR 13.160; 95 % CI 1.048-165.282) were significantly associated with bacteremia. Physicians should be aware that appropriate early management is necessary to prevent fatality in patients with these CT findings.

Spin90 deficiency increases CXCL13-mediated B cell migration.

SPIN90 regulates actin dynamics, which is important for cell migration control. CXCL13-mediated B cell migration is essential for B cell immune responses. In this study, we investigated the role of SPIN90 in CXCL13-mediated B cell migration using Spin90 gene-deficient mice. Our chemokinesis analysis and transwell cell migration assay showed that SPIN90 is involved in CXCL13-mediated B cell migration. Moreover, the level of CXCR5, which is CXCL13 receptor, was increased in SPIN90-deficient B cells compared with wild-type B cells. Overall, our data suggest that SPIN90 plays an important role in B cell immune responses through the regulation of CXCL13-mediated B cell migration.

Interrater reliability of the Korean version of the International Spinal Cord Injury Basic Pain Data Set.

OBJECTIVES: To provide a Korean translation of the International Spinal Cord Injury Basic Pain Data Set (ISCIBPDS) and evaluate the interrater reliability of the translated version. SETTING: Survey of community-dwelling people with spinal cord injury (SCI) in South Korea. METHODS: The initial translation was performed by two translators with an in-depth knowledge of SCI, and was then checked by another person with a similar background. A total of 115 SCI participants (87 men, 28 women; 48.4±14.1 years) were evaluated using the Korean version of the ISCIBPDS by two different raters. Intraclass correlation coefficient (ICC) or Cohen's kappa (κ) was used for analysis. RESULTS: All 115 participants had at least one pain problem on both surveys. Seventeen (14.8%) participants described their pain as a single pain problem to one rater while reporting the same pain as two or more different pain problems to the other rater. Twenty-two (19.1%) other participants reported their pain problems in a different order of severity on the surveys. The Korean version of the ISCIBPDS had acceptable interrater reliability, except in the 'limit activities (how much do you limit your activities in order to keep your pain from getting worse?)' item (ICC=0.318). CONCLUSION: Provision of criteria for pain separation may facilitate the consistent application of ISCIBPDS. In addition, the ISCIBPDS, which evaluated pain problems separately, reflected the multiple and complex characteristics of SCI-related pain; this was a strength of this data set.