Effect of time,temperature and pH on Mycobacterium tuberculosis culture positivity of gastric aspirate: An experimental study

BackgroundThe culture of gastric aspirate (GA) has been used for bacteriological confirmation of pulmonary tuberculosis in children and patients who are unable to expectorate. Sodium bicarbonate neutralization of gastric aspirates is commonly recommended to increase culture positivity. We aim to study Mycobacterium tuberculosis (MTB) culture positivity of GA collected from confirmed case of pulmonary tuberculosis after storing it at different temperature, pH & time.MethodsGA specimens from 865 patients of either sex predominately non-expectorating children/adults with suspected pulmonary TB were collected. Gastric lavage was performed in the morning after an overnight fasting (at least 6hrs fasting). The GA specimens were tested by CBNAAT (GeneXpert) and AFB microscopy & those who were positive on CBNAAT were further processed with MTB culture on Growth Indicator Tube (MGIT™) culture. pH neutralized and non-neutralized CBNAAT positive GA specimens were culture within 2 hours of collection and 24 hours after storage at 4 °C & room temperature.ResultsMTB was detected in 6.8% of collected GA specimens by CBNAAT. Culture positivity of neutralized GA specimens when processed within 2 hours of collection, was higher compared to paired non-neutralized GA specimens. Neutralized GA specimens had higher contamination rate than non-neutralized GA specimens. Storage of GA specimens at $Deg C had better culture yield than those stored at room temperature.ConclusionEarly neutralization of acid in Gastric aspirate (GA) is essential for better culture positivity of M. tuberculosis (MTB). If there is a delay in processing GA, it should be kept at 4 °C after neutralization; however, positivity decreases with time.     

Interleukin-37 gene polymorphism and susceptibility to pulmonary tuberculosis among Iraqi patients

BackgroundControl of tuberculosis (TB) depends on a balance between host's immune factors and bacterial evasion strategies. Interleukin-37 (IL-37) is among the immunomodulatory factors that have been proposed to influence susceptibility to tuberculosis.MethodsA case–control study was conducted on 105 patients with pulmonary TB (37 active, 41 multi-drug resistant and 27 relapse) and 79 healthy controls to determine serum levels and single nucleotide polymorphisms (SNPs) of IL-37. The IL-37 level was assessed with an enzyme-linked immunosorbent kit, while DNA-sequencing was used to detect SNPs in the promoter region of IL37 gene.Results: Median level of IL-37 was markedly increased in serum of TB patients compared to controls (325.0 vs. 169.1 pg/mL; p < 0.001). This increase was universally determined in subgroups of patients distributed according to gender, age groups, and clinical type of disease, while no significant differences were found between the subgroups in patients or controls. Analysis of receiver operating characteristic curve confirmed these findings and IL-37 occupied a very good area under the curve, which was 0.816 (95% CI = 0.744–0.888; p < 0.001). At a cut-off value of 185.6 pg/mL, the sensitivity and specificity of IL-37 were 81.0 and 82.3%, respectively. Of the nine detected SNPs (rs2466449 G/A, rs2466450 A/G, rs2723168 G/A, rs3811042 G/A, rs3811045 T/C, rs3811046 G/T, rs3811047 A/G, rs3811048 G/A and rs200782323 G/A), only rs3811048 showed a significant association with TB; the G allele showed a significantly decreased frequency in TB patients compared to controls (25.2 vs. 44.9%; OR = 0.41; p < 0.001). It was possible to assign five haplotypes, and three showed significant differences between patients and controls. Frequency of haplotype A-A-G-A-C-T-G-A-G (0.331 vs. 0.213; OR = 2.10; p = 0.015) was significantly increased in TB patients compared to controls. On the contrary, frequencies of haplotypes A-A-G-A-C-T-G-G-G (0.029 vs. 0.116; OR = 0.24; p = 0.01) and A-A-G-G-T-G-A-G-G (0.140 vs. 0.275; OR = 0.45; p = 0.015) were significantly decreased in patients.ConclusionsIL-37 was up-regulated in the serum of TB patients irrespective of their gender, age or clinical type of disease. SNPs in the promoter region of IL37 gene were proposed to be associated with susceptibility to TB.     

Is sterile pyuria another minor diagnostic criterion in urinary tuberculosis?

IntroductionComposite reference standard (CRS) is used for diagnosis of urinary tract tuberculosis (UTB). We examined if addition of a new ‘component test’ as minor criterion in the form of SP could improve the yield.MethodsWe identified patients admitted with a diagnosis of UTB from January 2009 to February 2016 from our patient database. We performed the validation of addition of a new ‘component’ “sterile pyuria” to the existing basic CRS.ResultsSP was seen in 50 patients (65.7%). Forty (52.6%) of these patients had one major criterion positive and 10 (13.1%) were diagnosed based on minor criteria. If SP was added as a minor criterion, an additional 8 (9.2%) patients would have been diagnosed based on minor criteria alone without the need for a histopathology.ConclusionsSP could improve the diagnostic yield of existing CRS by 8% with a 70% decrease in reliance on histopathology for diagnosis.     

A case of nonmucinous pulmonary micropapillary adenocarcinoma mimicking pulmonary tuberculosis

We report a rare case of nonmucinous pulmonary micropapillary adenocarcinoma mimicking pulmonary tuberculosis. A 68-year-old woman was hospitalized with hemoptysis. Her computed tomography revealed cavities and tree-in-bud appearance similar to the extensive form of pulmonary tuberculosis. However, histopathological findings of transbronchial biopsies of all lesions revealed adenocarcinoma and no pulmonary tuberculosis. Tree-in-bud appearance may relate to the floating micropapillary tufts in alveolar spaces. If pulmonary carcinoma is complicated by pulmonary tuberculosis, patients must be isolated and disadvantaged in cancer treatments. Therefore, recognizing this case may be therapeutically useful for respiratory physicians treating both diseases.     

Deformación miocárdica en miocardiopatía dilatada no isquémica mediante feature tracking. Factibilidad e implicaciones pronósticas

Introduction and objectivesMyocardial strain analysis could provide additional information to left ventricular ejection fraction (LVEF) in nonischemic dilated cardiomyopathy (NIDC). Our aim was to analyze the feasibility of left ventricular strain evaluation using cardiac magnetic resonance feature tracking (FT) in NIDC, and to determine its clinical and prognostic impact.MethodsWe retrospectively included consecutive patients with NIDC who underwent cardiac magnetic resonance. Left ventricular global longitudinal, circumferential and radial strain were obtained from standard cine sequences using FT analysis software. We evaluated their association with a composite endpoint (heart failure, implantable cardioverter-defibrillator in secondary prevention, or death).ResultsFT analysis could be performed in all of the 98 patients (mean age 68 ± 13 years, 72% men). Intra- and interobserver concordance was good for global longitudinal and circumferential strain but was worse for radial strain. Global circumferential strain was independently associated (OR, 1.16; P = .045) with LVEF normalization during follow-up and was the only morphological parameter independently associated with the composite endpoint (OR, 1.15; P = .038). A cutoff value < ?8.2% was able to predict the incidence of this event during follow-up (log-rank 4.6; P = .032).ConclusionsLeft ventricular strain analysis with FT is feasible and reproducible in NIDC. Global circumferential strain was able to predict LVEF recovery and the appearance of major cardiovascular events during follow-up.Full English text available from:www.revespcardiol.org/en     

The impact of diabetes mellitus on the pharmacokinetics of rifampicin among tuberculosis patients: A systematic review and meta-analysis study

Background and aimsDiabetes mellitus has a negative impact on the treatment outcome of tuberculosis, increasing the incidence of treatment failure and relapse. There is a scarcity of knowledge concerning the impact of diabetes mellitus on the pharmacokinetics of rifampicin. This study was conducted to evaluate the impact of diabetes mellitus on the pharmacokinetics of rifampicin among patients with tuberculosis.MethodsWe explored the Web of Science, Cochrane Library, PubMed, and Scopus databases for articles that reported the pharmacokinetic parameters of rifampicin in diabetic and nondiabetic patients with tuberculosis published until September 2020. Based on the presence or absence of heterogeneity, pooled estimates were calculated using a random or fixed effect model.ResultsSeven studies were relevant and included in this study. The Tmax of rifampicin increased in diabetic patients with tuberculosis compared with nondiabetic patients with tuberculosis (MD 0.84, 95% CI (0.32, 1.35), p = 0.002). No significant differences were detected in rifampicin Cmax (MD 0.18, 95% CI (?0.52, 0.88), p = 0.61), AUC0–24 (SMD -0.02, 95% CI (?0.34, 0.30), p = 0.90), Vd (MD -3.89, 95% CI (?11.17, 3.38), p = 0.29), CL (MD -0.13, 95%CI (?0.88, 0.61), p = 0.72), and MRT (MD 1.89, 95% CI (?0.03, 3.81), p = 0.05) between diabetic and nondiabetic patients with tuberculosis.ConclusionDiabetes mellitus increased the Tmax of rifampicin without further impact on other rifampicin pharmacokinetic parameters such as Cmax, AUC0–24, Vd, CL and MRT. Early therapeutic drug monitoring of rifampicin is necessary for diabetic tuberculosis patients.     

Myocardial Contractile Mechanics in Ischemic Mitral Regurgitation: Multicenter Data Using Stress Perfusion Cardiovascular Magnetic Resonance

BackgroundLeft ventricular (LV) ischemia has been variably associated with functional mitral regurgitation (FMR). Determinants of FMR in patients with ischemia are poorly understood.ObjectivesThis study sought to test whether contractile mechanics in ischemic myocardium underlying the mitral valve have an impact on likelihood of FMR.MethodsVasodilator stress perfusion cardiac magnetic resonance was performed in patients with coronary artery disease (CAD) at multiple centers. FMR severity was confirmed quantitatively via core lab analysis. To test relationship of contractile mechanics with ischemic FMR, regional wall motion and strain were assessed in patients with inducible ischemia and minimal (≤5% LV myocardium, nontransmural) infarction.ResultsA total of 2,647 patients with CAD were studied; 34% had FMR (7% moderate or greater). FMR severity increased with presence (P < 0.001) and extent (P = 0.01) of subpapillary ischemia: patients with moderate or greater FMR had more subpapillary ischemia (odds ratio [OR]: 1.13 per 10% LV; 95% CI: 1.05-1.21; P = 0.001) independent of ischemia in remote regions (P = NS); moderate or greater FMR prevalence increased stepwise with extent of ischemia and infarction in subpapillary myocardium (P < 0.001); stronger associations between FMR and infarction paralleled greater wall motion scores in infarct-affected territories. Among patients with inducible ischemia and minimal infarction (n = 532), wall motion and radial strain analysis showed impaired subpapillary contractile mechanics to associate with moderate or greater FMR (P < 0.05) independent of remote regions (P = NS). Conversely, subpapillary ischemia without contractile dysfunction did not augment FMR likelihood. Mitral and interpapillary dimensions increased with subpapillary radial strain impairment; each remodeling parameter associated with impaired subpapillary strain (P < 0.05) independent of remote strain (P = NS). Subpapillary radial strain (OR: 1.13 per 5% [95% CI: 1.02-1.25]; P = 0.02) and mitral tenting area (OR: 1.05 per 10 mm² [95% CI: 1.00-1.10]; P = 0.04) were associated with moderate or greater FMR controlling for global remodeling represented by LV end-systolic volume (P = NS): when substituting sphericity for LV volume, moderate or greater FMR remained independently associated with subpapillary radial strain impairment (OR: 1.22 per 5% [95% CI: 1.02-1.47]; P = 0.03).ConclusionsAmong patients with CAD and ischemia, FMR severity and adverse mitral apparatus remodeling increase in proportion to contractile dysfunction underlying the mitral valve.     

Detection of genital tuberculosis among women with infertility using best clinical practices in India: An implementation study

BackgroundDiagnosis of genital tuberculosis (TB) as a cause of infertility still remains a diagnostic dilemma for clinicians, as no standard guidelines exist. The recently proposed best practices for genital TB diagnosis have not been evaluated yet in India.ObjectivesTo implement best practices to diagnose and treat likely genital TB as a cause of infertility.MethodsBetween April 2016 and June 2018, consenting women seen at a tertiary hospital infertility clinic were assessed by thorough TB related clinical history, ultrasonography, tuberculin skin test (TST), and ESR. Those with suspected genital TB underwent laparohysteroscopy. Clinical and laboratory characteristics were compared between likely (microbiologically confirmed or probable TB) and unlikely (possible and no genital TB) genital TB. Fertility outcome was assessed among women initiated on anti-TB treatment (ATT).ResultsOf 185 women seeking infertility care, likely genital TB was identified among 29 (15.7%) women, with 6 (21%) confirmed and 23 (79%) probable genital TB. Compared to unlikely genital TB cases, the likely genital TB group were found to have past history of TB (p < 0.001); positive TST (p = 0.002) and elevated ESR (p = 0.001). Among the likely genital TB group, all 6 confirmed genital TB were started on ATT and 2 (33.3%) conceived. Of 5 probable genital TB started on ATT, 3 (60%) conceived.ConclusionApproximately 1/6th of women seeking infertility care met the criteria for likely genital TB. Conception among over-half of treated probable genital TB cases provides preliminary evidence that best clinical practices can be utilized, but needs further confirmatory studies.     

Prediction of the duration needed to achieve culture negativity in patients with active pulmonary tuberculosis using convolutional neural networks and chest radiography

BackgroundWe aimed to predict the duration needed to achieve culture negativity in patients with active pulmonary tuberculosis using convolutional neural networks (CNNs) and chest radiography.MethodsMedical records were searched for eligible patients with culture-confirmed active pulmonary tuberculosis. The eligible patients were randomly assigned to the training dataset group (N = 180) and the validation dataset group (N = 59). Posteroanterior X-ray radiographs in the standing position were obtained at diagnosis. The image data were augmented by a factor of 10 by randomly shifting and rotating the original image. Thus, 1800 images (112 × 112 pixels, 8-bit grayscale) from 180 patients in the training dataset group were used for training the CNN model. The model performance was evaluated on the validation dataset.ResultsThe values predicted by the CNN model were significantly associated with the actual values (Pearson's correlation coefficient 0.392, p = 0.002). The mean absolute error was 18.0. The visualization of the layer outputs suggested that the CNN model recognized some of the chest radiographic findings that were useful in predicting the duration needed to achieve culture negativity.ConclusionsThe CNN model was useful for predicting the duration needed to achieve culture negativity in active pulmonary tuberculosis, although the accuracy was unsatisfactory. This study suggests that chest radiography findings are as important as other clinical factors for prediction and could be learned by the machine.     

Risk factors of tuberculosis in Mizoram: First report of the possible role of water source

BackgroundVarious risk factors of tuberculosis have been studied across the globe, but these may be altered over time and can be specific to geographical regions and there is not much information available from Northeastern region of India. This study aims to investigate the various risk factors of tuberculosis and analyze the presence of any less-established risk factors.MethodsA total of 400 TB cases and 840 healthy controls were interviewed from December 2017 - June 2020. Logistic regression model was used to analyze associated risk factors. Patients were categorized into pulmonary and extrapulmonary TB.ResultsClinical presentation such as fever, cough, weight loss, chest pain and night sweats were more prominent among pulmonary TB patients. The most common mode of diagnosis among pulmonary and extrapulmonary TB were GeneXpert and X-ray, respectively. Tuberculosis was found to be strongly prevalent among patients from lower socio-economic status, less educated, unemployed and improper housing condition. Other risk factors associated were alcohol consumption, neighbours with TB, travel history, no BCG vaccine, mass gathering, and non-ideal weight. An interesting less-established risk factor that demands attention is the source of water supply (p-0.017, OR-2.313, CI: 1.160–4.613), which was significant in this study.ConclusionOur data suggests that apart from all the well-established risk factors for TB, water supply might play a crucial role towards the transmission of TB, since proper hospital waste water treatment is yet to be adopted in Mizoram, Northeast India. From a public health standpoint, this highlights the need for further research in this area.     

Evaluation of magnesium oxide and zinc oxide nanoparticles against multi-drug-resistance Mycobacterium tuberculosis

ObjectiveThe current study has evaluated the MICs and MBCs of ZnONPs, MgONPs, and MgONPs-ZnONPs against H₃₇Rv Mtb and MDR-Mtb.MethodsMixture, magnesium oxide nanoparticles (NPs) and zinc oxide (MgONPs-ZnONPs) were prepared. The microplate alamar blue (MABA) assay and the proportion method were used to evaluate of anti-tubercular activity against MDR-MTB. MTT test was done to MgONPs-ZnONPs against Vero and HepG₂ cell lines.ResultsThe MIC of MgONPs and ZnONPs were 0.195 and 0.468 μg mL^?1 against 10⁴ of H₃₇Rv Mtb. As well, 0.166 μg mL^?1 of MgONPs-ZnONPs was able to inhibit 10^?4 H₃₇Rv Mtb. The MIC of MgONPs against 10⁴ concentrations of MDR-Mtb was 12.5 μg mL^?1. The MIC of MgONPs/ZnONPs against 10⁴ concentrations of MDR-Mtb reached to 0.664 μg mL^?1. The MBC value of ZnONPs increased to 1.875 μg mL^?1 against 10^?4 concentrations of MDR-Mtb. Testing showed that the MBCs of MgONPs/ZnONPs reached to 1.328 μg mL^?1 against 10⁴ concentrations of MDR-Mtb. The IC₅₀ against MDR-TB was 0.779 μg mL^?1 for ZnONPs and 0.883 μg mL^?1 for MgONPs-ZnONPs. The MgONPs-ZnONPs was not toxic to Vero cell lines however ZnONPs could inhibit the Vero and HepG₂ cell lines.ConclusionWe found that ZnONPs and mixture MgONPs-ZnONPs not only have higher bactericide behavior but might have also synergistic effects against MDR-TB.     

Comparison of the chest computed tomography findings between patients with pulmonary tuberculosis and those with Mycobacterium avium complex lung disease

BackgroundSince the computed tomography (CT) findings of nontuberculous mycobacterial lung disease are similar to those of pulmonary tuberculosis (PTB), we often have difficulty differentiating the two. In this study, we compared the differences in chest CT findings and their locations between cases of PTB and Mycobacterium avium complex lung disease (MACLD).MethodsThe subjects were 100 MACLD patients and 42 PTB patients treated at our hospital from May 2005 to August 2015. The CT findings were retrospectively evaluated.ResultsPTB more frequently showed lung shadows with calcification inside the lesion, calcification of the mediastinal/hilar lymph node, and pleural effusion on CT than MACLD, while extensive bronchiectasis and granular/large shadows connected to bronchiectasis were more frequently observed with MACLD than PTB. For cavitary lesions, the thinnest part of the cavity wall with MACLD was thinner than that with PTB. Granular shadows, large shadows, and bronchiectasis were typically distributed to the right upper lobe and left upper division in PTB cases vs. the right intermediate lobe and left lingula in MACLD.ConclusionsChest CT findings would therefore be useful for distinguishing PTB and MACLD when typical findings are observed.     

CMR DENSE and the Seattle Heart Failure Model Inform Survival and Arrhythmia Risk After CRT

ObjectivesThis study sought to determine if combining the Seattle Heart Failure Model (SHFM-D) and cardiac magnetic resonance (CMR) provides complementary prognostic data for patients with cardiac resynchronization therapy (CRT) defibrillators.BackgroundThe SHFM-D is among the most widely used risk stratification models for overall survival in patients with heart failure and implantable cardioverter-defibrillators (ICDs), and CMR provides highly detailed information regarding cardiac structure and function.MethodsCMR Displacement Encoding with Stimulated Echoes (DENSE) strain imaging was used to generate the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) circumferential strain dyssynchrony parameter, and the SHFM-D was determined from clinical parameters. Multivariable Cox proportional hazards regression was used to determine adjusted hazard ratios and time-dependent areas under the curve for the primary endpoint of death, heart transplantation, left ventricular assist device, or appropriate ICD therapies.ResultsThe cohort consisted of 100 patients (65.5 [interquartile range 57.7 to 72.7] years; 29% female), of whom 47% had the primary clinical endpoint and 18% had appropriate ICD therapies during a median follow-up of 5.3 years. CURE-SVD and the SHFM-D were independently associated with the primary endpoint (SHFM-D: hazard ratio: 1.47/SD; 95% confidence interval: 1.06 to 2.03; p = 0.02) (CURE-SVD: hazard ratio: 1.54/SD; 95% confidence interval: 1.12 to 2.11; p = 0.009). Furthermore, a favorable prognostic group (Group A, with CURE-SVD <0.60 and SHFM-D <0.70) comprising approximately one-third of the patients had a very low rate of appropriate ICD therapies (1.5% per year) and a greater (90%) 4-year survival compared with Group B (CURE-SVD ≥0.60 or SHFM-D ≥0.70) patients (p = 0.02). CURE-SVD with DENSE had a stronger correlation with CRT response (r = −0.57; p < 0.0001) than CURE-SVD with feature tracking (r = −0.28; p = 0.004).ConclusionsA combined approach to risk stratification using CMR DENSE strain imaging and a widely used clinical risk model, the SHFM-D, proved to be effective in this cohort of patients referred for CRT defibrillators. The combined use of CMR and clinical risk models represents a promising and novel paradigm to inform prognosis and device selection in the future.     

Extent of pulmonary fibrosis on high-resolution computed tomography is a prognostic factor in patients with pleuroparenchymal fibroelastosis

BackgroundSeveral prognostic factors for pleuroparenchymal fibroelastosis (PPFE) have recently been reported. However, detailed high-resolution computed tomography (HRCT) findings have not yet been evaluated as prognostic factors. This study retrospectively investigated whether HRCT findings are prognostic factors in patients with PPFE compared to those with idiopathic pulmonary fibrosis (IPF).MethodsPatients with PPFE and IPF diagnosed at our hospital between January 2008 and December 2016 were enrolled. Clinical and HRCT characteristics were obtained. In addition to our patients, we also analyzed data of PPFE patients whose cause of death had been identified in previous studies.ResultsWe enrolled 15 patients with PPFE and 75 patients with IPF. Consolidation and maximum pleural thickening were significantly higher in patients with PPFE than in those with IPF (both P < .001). Fibrosis score, honeycomb area, and traction bronchiectasis were not significantly different between these patient groups but were significant prognostic factors in patients with PPFE in univariate analysis (P = .021, P = .017, and P = .014, respectively). The proportions of deaths by acute exacerbation or lung cancer were significantly lower in patients with PPFE than in those with IPF (P < .001 and P = .001, respectively), whereas death by respiratory failure was significantly more frequent in PPFE patients (P < .001).ConclusionsHRCT findings, such as fibrosis score, honeycomb area, and traction bronchiectasis, were independent prognostic factors in patients with PPFE. Respiratory failure, but not acute exacerbation and lung cancer, was the main cause of death in patients with PPFE.     

ATP7B Genotype and Chronic Liver Disease Treatment Outcomes in Wilson Disease: Worse Survival With Loss-of-Function Variants

Background and AimsAlthough a good genotype-phenotype correlation has not been established in Wilson disease (WD), patients with loss-of-function (LOF) ATP7B variants demonstrate different clinical and biochemical characteristics. We aim to describe long-term treatment outcomes in the chronic liver disease (CLD) phenotype and evaluate an association with LOF variants.MethodsThis was a single-center retrospective review of WD patients with at least 1 variant in ATP7B. Demographic, biochemical, genetic, and clinical parameters were obtained. The composite clinical endpoint of liver transplantation or death was used for probands with CLD phenotype on chelators.ResultsOf 117 patients with hepatic WD: 71 had CLD, 27 had fulminant hepatic failure requiring urgent liver transplantation, and 19 were diagnosed through family screening. Median age at diagnosis was 13.1 (interquartile range, 9.7–17.6) years. In total, 91 variants in ATP7B were identified in the study population. At least 1 LOF variant was present in 60 (51.3%) patients. During median follow-up of 10.7 (interquartile range, 6.7–18.9) years, 10 (14.1%) of the probands with CLD reached the composite endpoint. There was a worse transplant-free survival for patients prescribed chelation therapy in patients with at least 1 LOF variant (P = .03).ConclusionsPatients with WD and CLD phenotype on chelators, who have at least 1 LOF variant in ATP7B, have a worse prognosis during long-term follow up. This subgroup of patients requires close monitoring for signs of progressive liver disease. Sequencing of ATP7B may be used in the diagnosis of WD, and in addition, it may provide useful prognostic information for patients with hepatic WD.     

Association of Lipoprotein(a) With Recurrent Ischemic Events Following Percutaneous Coronary Intervention

ObjectivesThis study evaluated the association between elevated levels of lipoprotein(a) [Lp(a)] and risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI).BackgroundElevated levels of Lp(a) have been identified as an independent, possibly causal, risk factor for atherosclerotic cardiovascular disease in a general population study.MethodsA prospective single-center registry was used to identify 12,064 patients with baseline Lp(a) measurements who underwent PCI between 2003 and 2013. The primary outcomes were a composite of cardiovascular death, spontaneous myocardial infarction, and ischemic stroke.ResultsFrom the registry, 3,747 (31.1%) patients had high Lp(a) (>30 mg/dL) and 8,317 (68.9%) patients had low Lp(a) (≤30 mg/dL). During a median follow-up of 7.4 years, primary outcomes occurred in 1,490 patients, and the incidence rates of primary outcomes were 2.0 per 100 person-years in the high-Lp(a) group and 1.6 per 100 person-years in the low-Lp(a) group (adjusted hazard ratio [aHR]: 1.17; 95% confidence interval [CI]: 1.05-1.30; P = 0.004). Increased risk of recurrent ischemic cardiovascular events in the high-Lp(a) group was consistent in various subgroups including patients receiving statin treatment at discharge (aHR: 1.18; 95% CI: 1.03-1.34; P = 0.011). In addition, the risk of repeated revascularization was significantly higher in the high-Lp(a) group (aHR: 1.13; 95% CI: 1.02-1.25; P = 0.022).ConclusionsElevated levels of Lp(a) were significantly associated with the recurrent ischemic events in patients who underwent PCI. This study provides a rationale for outcome trials to test Lp(a)-lowering therapy for secondary prevention in patients undergoing PCI.     

Campylobacter fetus bacteremia complicated by multiple splenic abscesses and multivisceral signs in a renal transplant recipient: a case report and review of the literature

We report a rare case of Campylobacter fetus bacteremia in a 50-year-old woman following kidney transplantation. Bacteremia was complicated by multivisceral signs such as multiple splenic abscesses, bacterial hepatitis, erythema nodosum and reactive arthritis. Despite a prolonged diagnostic delay, the diagnosis was made on blood culture identification and the global outcome was favorable with adequate antibiotherapy. Reports in the literature describe a high rate of mortality for Campylobacter spp. septicemia, with most patients being immunocompromised. However, Campylobacter spp. has been rarely described in renal transplant patients. Moreover, a splenic septic localization due to Campylobacter spp. has been reported only once to our knowledge. Clinicians should be aware of the diagnostic difficulties related to the frequent negativity of stool samples in C. fetus septicemia, in order to implement a tailored medical strategy. Some data suggest that rapid introduction of adapted antibiotic therapy is associated with a reduction in mortality.     

Development of a CT image case database and content-based image retrieval system for non-cancerous respiratory diseases: Method and preliminary assessment

BackgroundTo evaluate the benefits of using a CT image case database (DB) with content-based image retrieval system for the diagnosis of typical non-cancerous respiratory diseases.MethodsUsing this DB, which comprised data on 191 cases covering 69 diseases, 933 imaging findings that contributed to differential diagnoses were annotated. Ten test cases were selected. Image similarity between each marked test case lesion and the lesions of the top 10 retrieved cases were assessed and classified as similar, somewhat similar, or dissimilar by two physicians in consensus. Additionally, the accuracy of five internal medicine residents’ abilities to interpret CT findings and provide disease diagnoses with and without the proposed system was evaluated by image interpretation experiments involving five test cases. The rates of concordance between the subjects’ interpretations and the correct answers prepared in advance by two specialists in consensus were converted into scores.ResultsThe mean (± SD) of image similarity among the 10 test cases was as follows: 5.1 ± 2.7 (similar), 2.9 ± 1.0 (somewhat similar), and 2.0 ± 2.4 (dissimilar). Using the proposed system, the subjects’ mean score for the correct interpretation of CT findings improved from 15.1 to 28.2 points (p = 0.131) and for the correct disease diagnoses, from 9.3 to 28.2 points (p = 0.034).ConclusionsAlthough this was a preliminary small-scale assessment, the results suggest that this system may contribute to an improved interpretation of CT findings and differential diagnosis of non-cancerous respiratory diseases, which are difficult to diagnose for inexperienced physicians.     

Pretomanid: A novel therapeutic paradigm for treatment of drug resistant tuberculosis

Tuberculosis is currently an anticipated driver of pandemic diseases. It remains an imminent issue accounting for about 1.4 million deaths annually across the world. Since the evolution of human entity drug susceptible tuberculosis was managed through potent first line therapies. Unfortunately, the emergence of newer multitude strains refractory amongst available drugs in Drug resistant TB has led to an emergence MDR-TB and XDR-TB. Moreover, the increasing incidence of drug susceptible TB in developing countries paved way to development of new guidelines for treating various form of tuberculosis. Furthermore, newer regimens are warranted to combat resistance that preferably cause a reduction in mortality. Until now, various ongoing trials are being carried in order to potentially evaluate the suitable novel drug candidates, repurposed drugs and host directed therapies that will optimistically be safe, easy to tolerate, cost effective and non-toxic that will modify the prospects for treating drug resistant TB and latent TB. In context, the current scenario seems to impose a significant challenge on health care researchers in the field of drug discovery owing to complexities, prolong treatment duration, and is cumbersome. Pretomanid is a novel drug with potent bactericidal properties emerging a key advancement used in combination along with other drug therapies This review details the role of pretomanid in treating tuberculosis and the clinical trials in adultsd.     

Decreased intracellular histamine concentration and basophil activation in anaphylaxis

BackgroundHistamine is a crucial mediator in the development of anaphylaxis. Although histamine is promptly degraded because of its short half-life in plasma, basophils, which release histamine, remain in the blood for days. To explore basophils as a potential marker and their involvement in the pathogenesis of anaphylaxis, we evaluated the intracellular histamine concentration and the degree of basophil activation in anaphylaxis patients.MethodsWe conducted a case–control study enrolling anaphylaxis patients and healthy controls. Basophil activation was evaluated by flow cytometry using up-regulation of CD203c expression.ResultsWe enrolled 23 patients and measured their blood histamine concentration. Basophil activation was analyzed in seven of 23 patients. The median intracellular histamine concentrations at admission were significantly lower in patients compared with controls (16.4 ng/mL [interquartile range {IQR}, 2.70 to 34.0] vs. 62.3 ng/mL [IQR, 46.0 to 85.1]; p < 0.0001). The median basophil number at admission was also significantly lower in patients compared with controls (2.21 cell/μL [IQR, 0.75 to 12.3] vs. 21.0 cell/μL [IQR, 19.5 to 28.9]; p = 0.027). CD203c expression was not up-regulated in any of the seven patients in vitro, but it was up-regulated in response to anti-IgE stimulation in vitro in two patients at admission and four patients at follow-up.ConclusionsAnaphylaxis is associated with a decrease in intracellular histamine, and a reduced number and reactivity of peripheral basophils. Impaired basophil function and a decrease in their number and intracellular histamine levels in the circulation may reflect the underlying mechanism, suggesting that basophils may be a marker of anaphylaxis.