On the Single-Molecule Magnetic Behavior of Linear Iron(I) Arylsilylamides.

The rational design of 3d-metal-based single-molecule magnets (SMM) requires a fundamental understanding of their intrinsic electronic and structural properties and how they translate into experimentally observable features. Here, we determined the magnetic properties of the linear iron(I) silylamides K{crypt}[FeL2] and [KFeL2] (L = -N(Dipp)SiMe3; crypt = 4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]hexacosan). For the former, slow-relaxation of the magnetization with a spin reversal barrier of Ueff = 152 cm-1 as well as a closed-waist magnetic hysteresis and magnetic blocking below 2.5 K are observed. For the more linear [KFeL2], in which the potassium cation is encapsulated by the aryl substituents of the amide ligands, the relaxation barrier and the blocking temperature increase to Ueff = 184 cm-1 and TB = 4.5 K, respectively. The increase is rationalized by a more pronounced axial anisotropy in [KFeL2] determined by dc-SQUID magnetometry. The effective relaxation barrier of [KFeL2] is in agreement with the energy spacing between the ground and first-excited magnetic states, as obtained by field-dependent IR-spectroscopy (178 cm-1), magnetic measurements (208 cm-1), as well as theoretical analysis (212 cm-1). In comparison with the literature, the results show that magnetic coercivity in linear iron(I) silylamides is driven by the degree of linearity in conjunction with steric encumbrance, whereas the ligand symmetry is a marginal factor.

Sphenopalatine ganglion volumetry in episodic cluster headache: from symptom laterality to cranial autonomic symptoms.

BACKGROUND: Sphenopalatine ganglion (SPG) is a peripheral structure that plays an important role in cluster headache (CH). Hence, a reliable method to measure the volume of SPG is crucial for studying the peripheral mechanism of CH. Additionally, the association between the clinical profiles and the morphology of the SPG in CH remains undetermined. This study aims to use the manual measurement of SPG volume to investigate its associations with CH, including headache laterality, cranial autonomic symptoms (CASs), presence of restlessness or agitation, and other clinical profiles. METHODS: We prospectively recruited consecutive CH patients at a tertiary medical center between April 2020 and April 2022. A total of eighty side-locked, in-bout, episodic CH patients and 40 non-headache healthy controls received 1.5 T brain MRI focusing on structural neuroimaging of the SPG. The manual measurement process for SPG was under axial and sagittal FIESTA imaging, with reference T2 weight images (sagittal and axial) for localization. The inter-observer agreement of the SPG volume (both sides of the SPG from CH patients and controls) between the two observers was calculated. In CH patients, clinical profiles and the number of CASs (range 0-5) were recorded to analyze their association with SPG volume. RESULTS: The inter-observer agreement between the two raters was excellent for the new SPG volumetry method at 0.88 (95% CI: 0.84-0.90, p < 0.001). The mean [SD] SPG volume was larger in CH patients than in non-headache controls (35.89 [12.94] vs. 26.13 [8.62] µL, p < 0.001). In CH patients, the SPG volume was larger on the pain side than on the non-pain side (38.87 [14.71] vs. 32.91 [12.70] µL, p < 0.001). The number of CASs was positively moderately correlated with the pain-side SPG volume (Pearson r = 0.320, p = 0.004) but not the non-pain side SPG volume (Pearson r = 0.207, p = 0.066). CONCLUSIONS: This proof-of-concept study successfully measured the SPG volume and demonstrated its associations with symptomatology in patients with episodic CH. The direct measurement of SPG provide insights into studies on peripheral mechanism of CH.

Influence of angioplasty and stenting on intracranial artery stenosis: preliminary results of high-resolution vessel wall imaging evaluation.

OBJECTIVES: To investigate whether the imaging changes on high-resolution vessel wall imaging (HR-VWI) in patients before and after percutaneous transluminal angioplasty and stenting (PTAS) contribute to predicting the clinical outcome. METHODS: The study included 24 severe intracranial artery stenosis (SICAS) patients undergoing PTAS with Wingspan Stent between 2018 and 2020 and had a 1-year follow-up. Three HR-VWI sessions (preprocedural, early [within 24 h], and delayed postprocedural [134.7 ± 27.1 days)]) in each subject were performed with 3-Tesla MRI. We evaluated periprocedural HR-VWI changes in patients with and without recurrent cerebral ischemic symptoms (RCIS) within 1-year follow-up. RESULTS: On CE-T1WI of the patients without RCIS, a significant decrease in enhanced area was observed on early postprocedural (0.04 ± 0.02 cm2, p = 0.001) and delayed postprocedural (0.04 ± 0.02 cm2; p = 0.001) HR-VWI compared to preprocedural (0.07 ± 0.02 cm2) HR-VWI. Patients with RCIS demonstrated no significant loss of enhanced area on CE-T1WI of early postprocedural HR-VWI (p = 0.180). Significant decreases in calibrated T1 signals were observed in both presence (1.77 ± 0.70 vs. 0.79 ± 0.52; p = 0.018) and absence (1.42 ± 0.62 vs. 0.83 ± 0.40; p = 0.001) of RCIS in early postprocedural HR-VWI. CONCLUSION: The preliminary results showed the presence of reduced contrast enhancement immediately after PTAS may indicate less recurrent stroke events within 1 year. Further studies are necessary to confirm the phenomena in a longer observation period. KEY POINTS: • Early postprocedural high-resolution vessel imaging (HR-VWI) within 24 h can effectively predict a 1-year outcome following intracranial stenting. • For stenotic lesions after stenting without reduced contrast enhancement on HR-VWI within 24 h may need closer clinical surveillance for potentially higher risk of stroke events within 1 year.

Risk of Hepatitis B Reactivation in Patients Receiving Ibrutinib: The National Veterans Affairs Cohort.

Background: Ibrutinib has been a first-line treatment for chronic lymphocytic leukemia since 2014. Case reports of hepatitis B virus (HBV) reactivation after ibrutinib initiation have been presented. The association between the risk of HBV reactivation and ibrutinib initiation remains unclear. This nationwide study aimed to estimate the incidence of HBV reactivation after ibrutinib initiation. Method: This study included patients who received ibrutinib between 1 February 2014 and 31 October 2019. Possible reactivations were searched by (1) changes in HBV surface antigen or HBV DNA from no data or negative status to positive after ibrutinib initiation, (2) alanine aminotransferase levels that were at least 3 times the baseline value after ibrutinib initiation, and (3) new antiviral prescriptions against HBV after ibrutinib initiation. Individual chart reviews were conducted to identify HBV reactivation attributed to ibrutinib. The cumulative incidence of HBV reactivation was calculated. Results: A total 4130 patients were eligible during the study period. Of these, patients with negative HBV core antibody (anti-HBcAb; n = 1670) and patients who were taking antivirals against HBV (n = 60) were excluded. There were 2219 patients without anti-HBcAb testing results. Among the remaining 181 patients with positive anti-HBcAb, 7 HBV reactivations were directly attributable to ibrutinib treatment after chart review, for a 3.9% cumulative incidence. Conclusions: Our study revealed a low cumulative incidence of HBV reactivation after ibrutinib initiation among patients with previous anti-HBcAb positivity, indicating a moderate risk of HBV reactivation.

Risk factors for treatment failure of polymyxin B monotherapy for carbapenem-resistant Klebsiella pneumoniae infections.

Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.

Impact of cefepime therapy on mortality among patients with bloodstream infections caused by extended-spectrum-ß-lactamase-producing Klebsiella pneumoniae and Escherichia coli.

Extended-spectrum-ß-lactamase (ESBL)-producing pathogens are associated with extensive morbidity and mortality and rising health care costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI), and no large studies have examined the impact of cefepime therapy. A retrospective 3-year study was performed at the Detroit Medical Center on adult patients with BSI due to ESBL-producing Klebsiella pneumoniae or Escherichia coli. Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. One hundred forty-five patients with BSI due to ESBL-producing pathogens, including K. pneumoniae (83%) and E. coli (16.5%), were studied. The mean age of the patients was 66 years. Fifty-one percent of the patients were female, and 79.3% were African-American. Fifty-three patients (37%) died in the hospital, and 92 survived to discharge. In bivariate analysis, the variables associated with mortality (P < 0.05) were presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included stay in the intensive care unit (odds ratio [OR], 2.17; 95% confidence interval [CI], 0.98 to 4.78), presence of a central-line catheter prior to positive culture (OR, 2.33; 95% CI, 0.77 to 7.03), presence of a rapidly fatal condition at the time of admission (OR, 5.13; 95% CI, 2.13 to 12.39), and recent prior hospitalization (OR, 1.92; 95% CI, 0.83 to 4.09). When carbapenems were added as empirical therapy to the predictor model, there was a trend between empirical carbapenem therapy and decreased mortality (OR, 0.61; 95% CI, 0.26 to 1.50). When added to the model, receipt of empirical cefepime alone (n = 43) was associated with increased mortality, although this association did not reach statistical significance (OR, 1.66; 95% CI, 0.71 to 3.87). The median length of hospital stay was shorter for patients receiving empirical cefepime than for those receiving empirical or consolidated carbapenem therapy. In multivariate analysis, empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend toward an increased mortality risk and empirical carbapenem therapy was associated with a trend toward decreased mortality risk.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

In Silico and In Vitro Analyses of Angiotensin-I Converting Enzyme Inhibitory and Antioxidant Activities of Enzymatic Protein Hydrolysates from Taiwan Mackerel (Scomber australasicus) Steaming Juice.

Mackerel (Scomber australasicus) steaming juice (MSJ) can be a good source of proteins. However, it is often treated as food waste during the canning process. The objective of this study was to investigate the Angiotensin-I converting enzyme (ACE-I) inhibitory and antioxidant activities from MSJ hydrolysates using in silico and in vitro approaches. Proteins extracted from MSJ were identified by proteomic techniques, followed by sulfate polyacrylamide gel electrophoresis (SDS-PAGE), in-gel digestion, tandem mass spectrometry and on-line Mascot database analysis. Myosin heavy chain (fast skeletal muscle), actin, myosin light chain 1 (skeletal muscle isoform), collagen alpha-2(I) chain, tropomyosin alpha-1 chain, beta-enolase, fructose-bisphosphate aldolase A and glyceraldehyde-3- phosphate dehydrogenase were identified and further analyzed using BIOPEP-UWM database. In silico results indicated that MSJ proteins had potential bioactive peptides of antioxidant and ACE-I inhibitory activities. MSJ was then hydrolyzed using six proteases (papain, pepsin, proteinase k, alcalase, bromelain, thermolysin). In particular, pepsin hydrolysates (5 mg/mL) showed the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (61.54%) among others. Alcalase hydrolysates (5 mg/mL) exhibited the highest metal chelating activity (89.76%) and proteinase K hydrolysates (5 mg/mL) indicated the highest reducing power activity (1.52 abs). Moreover, pepsin hydrolysates (0.1 mg/mL) possessed the highest ACE inhibitory activity (86.15%). Current findings suggest that MSJ hydrolysates can be a potential material to produce ACE-I inhibitory and antioxidant peptides as nutraceutical or pharmaceutical ingredients/products with added values.

Extended Remdesivir Infusion for Persistent Coronavirus Disease 2019 Infection.

Persistent severe acute respiratory syndrome coronavirus 2 infection is difficult to treat. Here, we report a case of 5-month persistent coronavirus disease 2019 in an immunocompromised patient who was successfully treated with 30 consecutive days of remdesivir. Prolonged remdesivir infusion with concurrent cycle threshold monitoring might provide a potential solution to cure these patients with difficult-to-treat infections.

Comparison of 2,3,5,4'-tetrahydroxystilbene-2-O-b-D-glucoside-induced proliferation and differentiation of dental pulp stem cells in 2D and 3D culture systems-gene analysis.

BACKGROUND/PURPOSE: Culture environments play a critical role in stem cell expansion. This study aimed to evaluate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-b-D-glucoside (THSG) on the proliferation and differentiation of human dental pulp stem cells (DPSCs) in 2-dimensional (2D) and 3-dimensional (3D) culture systems. MATERIALS AND METHODS: Human DPSCs were seeded in T25 flasks for 2D cultivation. For the 3D culture system, DPSCs were mixed with microcarriers and cultured in spinner flasks. Cells in both culture systems were treated with THSG, and cell proliferation was determined using a cell counter and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. In THSG-treated DPSCs, the genes associated with proliferation, adipogenesis, neurogenesis, osteogenesis, pluripotency, oncogenesis, and apoptosis were analyzed using real-time polymerase chain reactions. RESULTS: The spinner flask time-dependently improved cell numbers, cell viability, and expansion rates in THSG-treated DPSCs. In both the T25 and spinner flasks, the messenger RNA (mRNA) levels of proliferation, osteogenesis, and pluripotent-related genes had a significant maximum expression with 10 µM THSG treatment. However, 0.1 µM of THSG may be the most suitable condition for triggering neurogenesis and adipogenesis gene expression when DPSCs were cultured in spinner flasks. Furthermore, the number of oncogenes and apoptotic genes decreased considerably in the presence of THSG in both the T25 and spinner flasks. CONCLUSION: The spinner flask bioreactor combined with THSG may upregulate proliferation and lineage-specific differentiation in DPSCs. Thus, the combination can be used to mass-produce and cultivate human DPSCs for regenerative dentistry.

Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan.

Carbapenem-resistant Klebsiella pneumoniae has spread worldwide and throughout the United States. Colistin is used extensively to treat infections with this organism. We describe a cluster of colistin-resistant, carbapenem-resistant K. pneumoniae infection cases involving three institutions in Detroit, MI. A cluster of five cases of colistin-resistant, carbapenem-resistant K. pneumoniae was identified at Detroit Medical Center (DMC) from 27 July to 22 August 2009. Epidemiologic data were collected, and transmission opportunities were analyzed. Isolates were genotyped by using pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR. Data regarding the use of colistin were obtained from pharmacy records. The index case of colistin-resistant, carbapenem-resistant K. pneumoniae was followed 20 days later by four additional cases occurring in a 6-day interval. All of the patients, at some point, had stayed at one particular institution. The mean number of opportunities for transmission between patients was 2.3 ± 0.5, and each patient had at least one opportunity for transmission with one of the other patients. Compared to 60 colistin-susceptible, carbapenem-resistant K. pneumoniae controls isolated in the previous year at DMC, case patients were significantly older (P = 0.05) and the carbapenem-resistant K. pneumoniae organisms isolated from them displayed much higher MICs to imipenem (P < 0.001). Colistin use was not enhanced in the months preceding the outbreak. Genotyping revealed two closely related clones. This report of a colistin-resistant, carbapenem-resistant K. pneumoniae outbreak is strongly linked to patient-to-patient transmission. Controlling the spread and novel emergence of bacteria with this phenotype is of paramount importance.

2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside-stimulated dental pulp stem cells-derived conditioned medium enhances cell activity and anti-inflammation.

BACKGROUND/PURPOSE: Dental pulp stem cells (DPSCs) contribute to the regeneration of various tissues and have superior proliferation, immune privilege, and anti-inflammation properties to other mesenchymal stem cells. 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) not only enhances the aforementioned properties of DPSCs but also promotes self-renewal and reprogramming-like ability. However, whether THSG enhances the aforementioned properties and abilities through direct or indirect interaction mechanisms remains unclear. To address this knowledge gap, we examined the effects of THSG-stimulated DPSC-derived conditioned medium (THSG-CM) on the activity and anti-inflammation properties of cells. MATERIALS AND METHODS: DPSCs were treated with various concentrations of THSG to produce THSG-CM, which was then collected, analyzed, and lyophilized. A cytokine profiling antibody assay was used to compare protein components between THSG-treated and nontreated CM. Human skin fibroblasts (HSFs) and human gingival fibroblasts (HGFs) were used to investigate the effect of THSG-CM on cell proliferation, anti-inflammation, and wound healing abilities; for this investigation, MTS assay, quantitative real-time PCR analysis, and 2-well silicone inserts wound model were conducted. RESULTS: We observed that THSG enhanced the secretion of growth- and immune-associated proteins in THSG-CM and increased the proliferation of HSFs and HGFs. Furthermore, THSG-CM significantly attenuated lipopolysaccharide-stimulated mRNA levels of cytokines in both cells and improved wound healing abilities. CONCLUSION: We conclude that THSG-CM had more beneficial effects on cell activity and anti-inflammation in the HSFs and HGFs than DPSC-derived CM. DPSC-derived CM can be developed into a cell-free regenerative strategy in the future, and its therapeutic efficacy may be improved by THSG-CM.

2,3,5,4'-tetrahydroxystilbene-2-O-b-D-glucoside triggers the pluripotent-like possibility of dental pulp stem cells by activating the JAK2/STAT3 axis: Preliminary observations.

Abstract. BACKGROUND/PURPOSE: Although 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-glucoside (THSG) reportedly has anti-inflammatory properties, its role in inducing the dedifferentiation of human dental pulp stem cells (DPSC) into pluripotent-like stem cells remains to be determined. The purpose of this study is to evaluate the effects of THSG on the pluripotent-like possibility and mechanism of DPSC. MATERIALS AND METHODS: DPSCs were treated with THSG, and cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTS) assay. Real-time polymerase chain reaction was used to analyze the mRNA expression levels of pluripotency-associated genes and oncogenes and to detect telomerase activity in the cells. Embryoid body formation assay was conducted, and pluripotency-related proteins were identified using Western blotting. Data were analyzed using one-way analysis of variance. RESULTS: Cell viability, telomerase activity, and embryoid body formation were enhanced in THSG-treated DPSCs. The mRNA expression levels of pluripotent-like genes (including Nanog homeobox [NANOG], SRY-box 2 [SOX2], and POU class 5 homeobox 1 [POU5F1/OCT4]) significantly increased after THSG treatment. The expression levels of pluripotency-related genes (Janus kinase-signal transducer 2 [JAK2] and signal transducer and activator of transcription 3 [STAT3]) increased, whereas those of oncogenes (Ras, SRC, HER2, and C-sis) decreased. Furthermore, the expression levels of the phosphorylated JAK2 and STAT3 proteins significantly increased after THSG treatment. CONCLUSION: THSG treatment may enhance the pluripotent-like possibility of DPSC through the JAK2/STAT3 axis. Hence, it may be used as an alternative cell-based therapeutic strategy in regenerative dentistry.

Ambiphilicity of a mononuclear cobalt(III) superoxo complex.

Addition of HOTf to a mixture of CoIII(BDPP)(O2˙) (1, H2BDPP = 2,6-bis((2-(S)-diphenylhydroxylmethyl-1-pyrrolidinyl)methyl)pyridine) and Cp*2Fe produced H2O2 in high yield implying formation of CoIII(BDPP)(OOH) (3), and reaction of Sc(OTf)3 with the same mixture gave a peroxo-bridged CoIII/ScIII5. These findings demonstrate the ambiphilic property of CoIII-superoxo 1.

Influence of Vertebrobasilar Stenotic Lesion Rigidity on the Outcome of Angioplasty and Stenting.

Stenotic lesion rigidity (SLR) has an unclear influence on the outcome of percutaneous transluminal angioplasty and stenting (PTAS) for intracranial arterial stenosis. This study evaluated the outcome of PTAS and the relationship of vertebrobasilar SLR to features on vessel wall MRI (VW-MRI) for identifying pathologies of vertebrobasilar stenosis (VBS) and evaluating PTAS outcome. We retrospectively evaluated the results of PTAS in 31 patients with severe VBS. Stenotic lesions were classified as soft (based on predilatation pressure [PP] ≦ 4 atm) in 15 patients or hard (PP >4 atm) in 16 patients. We examined the relationship of SLR to clinical and MR findings. Patients with hard vs soft lesions had atherosclerosis (8/16 [50.0%] vs 2/15 [13.3%]), dissection (0/16 [0.0%] vs 12/15 [80.0%]), and dissection in atherosclerosis (8/16 [50.0%] vs 1/15 [6.7%], P < 0.0001); high intensity signal on the T1WI of VW-MRI (5/16 [31.3%] vs 14/15 [93.3%]) and iso- to low intensity signal (11/16 [68.7%] vs 1/15 [6.7], P = 0.001), and significant in-stent restenosis (>50%) in 5/15 (33.3%) vs 0/15 (0.0%) (P = 0.0421) in the 30 patients who successfully completed PTAS. Vertebrobasilar SLR correlated well with lesion etiology, findings on VW-MRI, and PTAS outcome. Patients with hard stenotic lesions need close follow-up after PTAS.

Meta-analysis: increased mortality associated with hepatitis C in HIV-infected persons is unrelated to HIV disease progression.

BACKGROUND: It is unclear whether coinfection with hepatitis C virus (HCV) increases mortality in patients with human immunodeficiency virus (HIV) infection during the era of highly active antiretroviral therapy (HAART). With use of a meta-analysis, we estimated the effect of HCV infection on HIV disease progression and overall mortality in the pre-HAART and HAART eras. METHOD: The PubMed and EMBASE databases were searched for studies published through 30 April 2008. Additional studies were identified from cited references. Studies reporting disease progression or mortality among HCV-HIV coinfected patients were selected. Cross-sectional studies, studies without HCV-negative control subjects, and studies involving children and/or patients who had undergone liver transplantation were excluded. Two authors reviewed articles and extracted data on the demographic characteristics of study populations and risk estimates. Meta-regression was used to explore heterogeneity. RESULTS: Ten studies from the pre-HAART era and 27 studies from the HAART era were selected. In the pre-HAART era, the risk ratio for overall mortality among patients with HCV-HIV coinfection, compared with that among patients with HIV infection alone, was 0.68 (95% confidence interval [CI], 0.53-0.87). In the HAART era, the risk ratio was 1.12 (95% CI, 0.82-1.51) for AIDS-defining events and 1.35 (95% CI, 1.11-1.63) for overall mortality among coinfected patients, compared with that among patients with HIV monoinfection. CONCLUSIONS: HCV coinfection did not increase mortality among patients with HIV infection before the introduction of HAART. In contrast, in the HAART era, HCV coinfection, compared with HIV infection alone, increases the risk of mortality, but not the risk of AIDS-defining events. Future studies should determine whether successful treatment of HCV infection could reduce this excess risk of mortality in coinfected patients.

Cigarette smoking and colorectal cancer incidence and mortality: systematic review and meta-analysis.

The association between cigarette smoking and colorectal cancer (CRC) has been controversial. To synthesize the available data, we conducted a comprehensive meta-analysis of all prospective studies. A total of 36 studies were included in our meta-analysis. We examined the association between smoking and CRC, colon cancer and rectal cancer in terms of incidence and mortality. Separate analyses were conducted for smoking status, daily cigarette consumption, duration, pack-years and age of initiation. Relative to nonsmokers, current and former smokers had a significantly increased risk of CRC incidence and mortality, respectively. When CRC data were combined with colon/rectal cancer data, current smokers had a significantly increased risk of CRC incidence. All 4 dose-response variables examined-daily cigarette consumption (RR = 1.38 for an increase of 40 cigarettes/day), duration (RR = 1.20 for an increase of 40 years of duration), pack-years (RR = 1.51 for an increase of 60 pack-years) and age of initiation (RR = 0.96 for a delay of 10 years in smoking initiation)-were significantly associated with CRC incidence (all p-values < 0.0001). The relationship between duration of smoking and rectal cancer incidence was also significant. Among the subset of studies that distinguished cancer by site, a higher risk was seen for rectal cancer than for colon cancer for all analyses. Among prospective studies, a consistent association exists between smoking and CRC. The association is stronger for rectal cancer than for colon cancer in the subset of studies that differentiated cancer by site.

Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma: Results From a Global Multicohort Study.

PURPOSE: Conflicting evidence indicates that HIV seropositivity may influence the outcome of patients with hepatocellular carcinoma (HCC), a leading cause of mortality in people with HIV. We aimed to verify whether HIV affected the overall survival (OS) of patients with HCC, independent of treatment and geographic origin. PATIENTS AND METHODS: We designed an international multicohort study of patients with HCC accrued from four continents who did not receive any anticancer treatment. We estimated the effect of HIV seropositivity on patients' OS while accounting for common prognostic factors and demographic characteristics in uni- and multivariable models. RESULTS: A total of 1,588 patients were recruited, 132 of whom were HIV positive. Most patients clustered within Barcelona Clinic Liver Cancer (BCLC) C or D criteria (n = 1,168 [74%]) and Child-Turcotte-Pugh (CTP) class B (median score, 7; interquartile range [IQR], 3). At HCC diagnosis, the majority of patients who were HIV-positive (n = 65 [64%]) had been on antiretrovirals for a median duration of 8.3 years (IQR, 8.59 years) and had median CD4+ cell counts of 256 (IQR, 284) with undetectable HIV RNA (n = 68 [52%]). OS decreased significantly throughout BCLC stages 0 to D (16, 12, 7.5, 3.1, and 3 months, respectively; P < .001). Median OS of patients who were HIV-positive was one half that of their HIV-uninfected counterparts (2.2 months [bootstrap 95% CI, 1.2 to 3.1 months] v 4.1 months [95% CI, 3.6 to 4.4 months]). In adjusted analyses, HIV seropositivity increased the hazard of death by 24% ( P = .0333) independent of BCLC ( P < .0001), CTP ( P < .0001), α-fetoprotein ( P < .0001), geographical origin ( P < .0001), and male sex ( P = .0016). Predictors of worse OS in patients who were HIV-positive included CTP ( P = .0071) and α-fetoprotein ( P < .0001). CONCLUSION: Despite adequate antiretroviral treatment, HIV seropositivity is associated with decreased survival in HCC, independent of stage, anticancer treatment, and geographical origin. Mechanistic studies investigating the immunobiology of HIV-associated HCC are urgently required.

The current role of 1.5T non-contrast 3D time-of-flight magnetic resonance angiography to detect intracranial steno-occlusive disease.

BACKGROUND/PURPOSE: This study was performed to evaluate the role of non-contrast 3D time-of-flight (TOF) magnetic resonance angiography (MRA) to detect and quantify intracranial steno-occlusive disease. METHODS: Between April 2004 and January 2006, 45 patients with both 1.5T TOF MRA and digital subtraction angiography (DSA) performed within a 30-day interval were included. We evaluated the following intracranial arterial segments: petrous internal carotid artery (ICA), cavernous ICA, supraclinoid ICA, M1 of middle cerebral artery, A1 of anterior cerebral artery, P1 of posterior cerebral artery, basilar artery, and distal vertebral artery. In total, 675 arterial segments were evaluated and categorized as negative, moderate-1 (3049% stenosis), moderate-2 (5069%), severe (7099% stenosis, including gap sign on MRA), and occlusion. RESULTS: The sensitivity and specificity of TOF MRA for > 29% stenosis and > 49% stenosis were 94%, 96% and 95%, 96%, respectively; while sensitivity and specificity for occlusion lesions were both 100%. However, 44 segments (37% of diseased segments) were overestimated by MRA, including 20 false-positive stenoses (which occurred in 10 [22%] patients) and 24 overestimated stenosis degree. The gap sign as severe stenosis only showed about 21% sensitivity and 41% specificity. Seven lesions were underestimated by MRA: three arterial segments were out of the field of MRA examination, and four were moderate-1stenosis on DSA. CONCLUSION: TOF MRA has high sensitivity and specificity in detecting all categories of stenosis degree and occlusion. However, it tends to overestimate lesions. Therefore, MRA can be considered as a screening study. Confirmation with other studies is recommended in doubtful cases.

Central Nervous System Melioidosis Mimics Malignancy: A Case Report and Literature Review.

BACKGROUND: Central nervous system (CNS) melioidosis is notorious because of the difficulty in bacteria eradication and the destruction of brain structures. Early manifestation of CNS melioidosis mimics malignancy or stroke. We present a case of CNS melioidosis that initially manifested as malignancy. CASE DESCRIPTION: A 30-year-old man presented with sudden onset of left limb weakness and seizure. Computed tomography of the brain showed a low-density lesion over the right parietal lobe, and magnetic resonance imaging showed a well-enhanced lobulated lesion. Neuronavigation-guided open surgery was performed but failed to find a malignancy. The patient presented 3 days later with sudden loss of consciousness, pupil dilation, and high fever. Emergent craniectomy was performed for severe right hemisphere swelling with midline shift. After craniectomy, pus was found in the previous operative field. Burkholderia pseudomallei was cultured from pus and blood samples 1 week after collection. The brain lesion developed into an organized abscess and led to mass effect and ventriculitis. Extraventricular drainage and débridement was performed repeatedly accompanied by systemic and intraventricular antibiotic administration. After 4 months of treatment, the patient achieved a complete consciousness recover while left hemiparesis. CONCLUSIONS: CNS melioidosis requires accurate pathogen identification and appropriate long-term antibiotic treatment for eradication of bacteria and prevention of relapse. Débridement and adequate drainage provide better infection control and outcome.