Search

We study the effect of cosmic ray (CR) acceleration in the massive compact star cluster Westerlund 1 in light of its recent detection in γ-rays. Recent observations reveal a 1/ r radial distribution of the CR energy density. Here, we theoretically investigate whether or not this profile can help to distinguish between (1) continuous CR acceleration in the star cluster stellar wind-driven shocks and (2) discrete CR acceleration in multiple supernovae (SNe) shocks – which are often debated in the literature. Using idealized two-fluid simulations and exploring different acceleration sites and diffusion coefficients, we obtain the CR energy density profile and luminosity to find the best match for the γ-ray observations. We find that the inferred CR energy density profiles from observations of γ-ray luminosity and mass can be much different from the true radial profile. CR acceleration at either the cluster core region or the wind termination shock can explain the observations, if the diffusion coefficient is κ cr ∼ 1027 cm2 s−1 and a fraction of |${\approx}10-20{{\ \rm per\ cent}}$| of the shock power/post-shock pressure is deposited into the CR component. We also study the possibility of discrete SNe explosions being responsible for CR acceleration and find that with an injection rate of 1 SN in every ∼0.03 Myr, one can explain the observed γ-ray profile. This multiple SN scenario is consistent with X-ray observations only if the thermal conductivity is close to the Spitzer value. [ABSTRACT FROM AUTHOR]

Cosmic rays (CRs) are frequently modelled as an additional fluid in hydrodynamic (HD) and magnetohydrodynamic (MHD) simulations of astrophysical flows. The standard CR two-fluid model is described in terms of three conservation laws (expressing conservation of mass, momentum, and total energy) and one additional equation (for the CR pressure) that cannot be cast in a satisfactory conservative form. The presence of non-conservative terms with spatial derivatives in the model equations prevents a unique weak solution behind a shock. We investigate a number of methods for the numerical solution of the two-fluid equations and find that, in the presence of shock waves, the results generally depend on the numerical details (spatial reconstruction, time stepping, the CFL number, and the adopted discretization). All methods converge to a unique result if the energy partition between the thermal and non-thermal fluids at the shock is prescribed using a subgrid prescription. This highlights the non-uniqueness problem of the two-fluid equations at shocks. From our numerical investigations, we report a robust method for which the solutions are insensitive to the numerical details even in absence of a subgrid prescription, although we recommend a subgrid closure at shocks using results from kinetic theory. The subgrid closure is crucial for a reliable post-shock solution and also its impact on large-scale flows because the shock microphysics that determines CR acceleration is not accurately captured in a fluid approximation. Critical test problems, limitations of fluid modelling, and future directions are discussed. [ABSTRACT FROM AUTHOR]

Using an idealized set-up, we investigate the dynamical role of cosmic rays (CRs) in the early stages of galactic outflows for galaxies of halo masses 108, 1011, and 1012 M⊙. The outflow is launched from a central region in the galactic disc where we consider three different constant star formation rates (0.1, 1, and 10 |$\mathrm{M}_\odot \, \mathrm{yr}^{-1}$|⁠) over a dynamical time-scale of 50 Myr. We determine the temperature distribution of the gas and find that CRs can reduce the temperature of the shocked gas, which is consistent with previous results. However, we show that CRs do not have any noticeable effect on the mass loading by the outflow. We find that CRs can reduce the size of the outflow, which contradicts previous claims of efficient dynamical impact of CRs; however, it is consistent with earlier theoretical models of CR-driven blastwave as well as stellar wind. We discuss the dependence of our results on CR injection prescriptions and compare them with earlier studies. We conclude that in the early stages of galactic outflows the dynamical role of CRs is not important. [ABSTRACT FROM AUTHOR]

Cosmic ray (CR) sources leave signatures in the isotopic abundances of CRs. Current models of Galactic CRs that consider supernovae (SNe) shocks as the main sites of particle acceleration cannot satisfactorily explain the higher 22Ne/20Ne ratio in CRs compared to the interstellar medium. Although stellar winds from massive stars have been invoked, their contribution relative to SNe ejecta has been taken as a free parameter. Here, we present a theoretical calculation of the relative contributions of wind termination shocks (WTSs) and SNe shocks in superbubbles, based on the hydrodynamics of winds in clusters, the standard stellar mass function, and stellar evolution theory. We find that the contribution of WTSs towards the total CR production is at least |$25{{\ \rm per\ cent}}$|⁠ , which rises to |$\gtrsim 50{{\ \rm per\ cent}}$| for young (≲10 Myr) clusters, and explains the observed 22Ne/20Ne ratio. We argue that since the progenitors of apparently isolated supernovae remnants (SNRs) are born in massive star clusters, both WTS and SNe shocks can be integrated into a combined scenario of CRs being accelerated in massive clusters. This scenario is consistent with the observed ratio of SNRs to γ-ray bright (L γ ≳ 1035 erg s−1) star clusters, as predicted by star cluster mass function. Moreover, WTSs can accelerate CRs to PeV energies, and solve other long-standing problems of the standard SN paradigm of CR acceleration. [ABSTRACT FROM AUTHOR]

In this study, we report microfluidic shear rheology and wall-slip using the 3D-resolved flow kinematics obtained from digital holography microscopy (DHM). We computationally reconstruct the recorded holograms to visualize the tracer imbued flow volume in linear microchannels, followed by the implementation of particle tracking velocimetry (PTV) to quantitate spatially resolved velocity fields in 3D. In order to select optimal parameters for DHM-PTV characterization of viscoelastic fluids, we studied the effect of the hologram recording distance, seeding density, and particle size. Using the optimal parameters, we show quantitative characterization of the shear rheology from the velocity fields without any a priori assumptions of wall boundary conditions or constitutive equation. The viscosity vs shear rate data for Newtonian and polyethylene oxide (PEO) solutions could be measured in the range of ≈0.05 to 20 000 s−1 with just three input pressures using sample volumes as low as 20 µl. These data from holographic shear rheometry were found to be in good agreement with computational fluid dynamics simulations and macrorheometry. With respect to the wall-slip, we find that highly viscoelastic PEO solutions can show slip lengths in the order of few microns. Finally, we discuss holographic visualization of particle migration in microfluidic flows, which can limit flow field access, whereas at the same time provide a fingerprint of the suspending fluid rheology. [ABSTRACT FROM AUTHOR]

We report a disposable microfluidic extensional viscometer based on an optimized hyperbolic contraction–expansion geometry. This "eCapillary" device works by measuring pressure drop as a function of flow rate while accounting for viscous contribution to the pressure drop. The viscometer operates by applying a constant pressure and using an image-based approach to measure the flow rate. The device is fabricated entirely out of polydimethylsiloxane with no embedded sensors, making it disposable. We tested our approach using weakly elastic polymer solutions whose relaxation times were characterized by dripping-on-substrate rheology. Flow visualization was used to determine the onset of inertioelastic instabilities in the eCapillary device, thereby establishing the operating limits for extensional rheological measurements. Holography-based velocimetry analysis showed that extensional strain rate is uniform in a narrow section of the contraction throat necessitating correction for the shear contribution to the measured pressure drop. We observed the onset of extensional thickening to occur at Deborah number ≈ 1 and found that the apparent extensional viscosities are 2–4 orders of magnitude higher than the shear viscosities. Finally, we compared our data with those from other microfluidic extensional viscometers reported in the literature and found good agreement. [ABSTRACT FROM AUTHOR]

We use 1D and 3D two-fluid cosmic ray (CR) hydrodynamic simulations to investigate the role of CRs in the vicinity of a compact young star cluster. We model a self-gravitating cloud (density profile ρ∝ r −1), include important thermal and non-thermal processes, and explore two different CR injection scenarios. We show that if internal shocks in the wind-driving region are the main site for CR acceleration, then the resulting γ-ray luminosity (L γ) can reach ≈5 per cent of the mechanical luminosity (L w), independent of the fraction of wind energy (∼1–20 per cent) injected into CRs. In contrast, if the forward/reverse shock of a bubble is the injection site then L γ increases linearly with the CR injection fraction, as expected analytically. We find that the X-ray luminosity (L x) in the forward/reverse shock injection scenario is ≳ 10−3 L w, which is ∼10 times larger than in the central wind-driving injection case. We predict the corresponding range of the synchrotron radio luminosity. We show how multi-wavelength observations can constrain the CR parameters. Comparing the predicted multi-wavelength luminosities with those of 30 Doradus and Westerlund 2 we identify the reverse shock as the most probable CR injection site. We do not find significant dynamical impact of CRs in our models. [ABSTRACT FROM AUTHOR]

Using analytic methods and 1D two-fluid simulations, we study the effect of cosmic rays (CRs) on the dynamics of interstellar superbubbles (ISBs) driven by multiple supernovae (SNe)/stellar winds in OB associations. In addition to CR advection and diffusion, our models include thermal conduction and radiative cooling. We find that CR injection at the reverse shock or within a central wind-driving region can affect the thermal profiles of ISBs and hence their X-ray properties. Even if a small fraction (10-20 per cent) of the total mechanical power is injected into CRs, a significant fraction of the ram pressure at the reverse shock can be transferred to CRs. The energy transfer becomes efficient if (1) the reverse shock gas Mach number exceeds a critical value (Mth ≳ 12) and (2) the CR acceleration time-scale τacc ∼ κcr/v² is shorter than the dynamical time, where κcr is a CR diffusion coefficient and v is the upstream velocity. We show that CR affected bubbles can exhibit a volume-averaged hot gas temperature 1-5 × 106 K, lower by a factor of 2 - 10 than without CRs. Thus, CRs can potentially solve the long-standing problem of the observed low ISB temperatures. [ABSTRACT FROM AUTHOR]

Energetic winds and radiation from massive star clusters push the surrounding gas and blow superbubbles in the interstellar medium (ISM). Using 1D hydrodynamic simulations, we study the role of radiation in the dynamics of superbubbles driven by a young star cluster of mass 106 M⊙. We have considered a realistic time evolution of the mechanical power as well as radiation power of the star cluster, and detailed heating and cooling processes. We find that the ratio of the radiation pressure on the shell (shocked ISM) to the thermal pressure (∼107 K) of the shocked-wind region is almost independent of the ambient density, and it is greater than unity before ≲1 Myr. We explore the parameter space of density and dust opacity of the ambient medium, and find that the size of the hot gas (∼107 K) cavity is insensitive to the dust opacity [σd ≈ (0.1–1.5) × 10−21 cm2], but the structure of the photoionized (∼104 K) gas depends on it. Most of the radiative losses occur at ∼104 K, with sub-dominant losses at ≲103 K and ∼106–108 K. The superbubbles can retain as high as ∼10 per cent of its input energy, for an ambient density of 103 mH cm−3. We discuss the role of ionization parameter and recombination-averaged density in understanding the dominant feedback mechanism. Finally, we compare our results with the observations of 30 Doradus. [ABSTRACT FROM AUTHOR]

The rich diversity of man-made complex fluids and naturally occurring biofluids is opening up new opportunities for investigating their flow behavior and characterizing their rheological properties. Steady shear viscosity is undoubtedly the most widely characterized material property of these fluids. Although widely adopted, macroscale rheometers are limited by sample volumes, access to high shear rates, hydrodynamic instabilities, and interfacial artifacts. Currently, microfluidic devices are capable of handling low sample volumes, providing precision control of flow and channel geometry, enabling a high degree of multiplexing and automation, and integrating flow visualization and optical techniques. These intrinsic advantages of microfluidics have made it especially suitable for the steady shear rheology of complex fluids. In this paper, we review the use of microfluidics for conducting shear viscometry of complex fluids and biofluids with a focus on viscosity curves as a function of shear rate. We discuss the physical principles underlying different microfluidic viscometers, their unique features and limits of operation. This compilation of technological options will potentially serve in promoting the benefits of microfluidic viscometry along with evincing further interest and research in this area. We intend that this review will aid researchers handling and studying complex fluids in selecting and adopting microfluidic viscometers based on their needs. We conclude with challenges and future directions in microfluidic rheometry of complex fluids and biofluids. [ABSTRACT FROM AUTHOR]

The author explores evidence of the existence of cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Topics discussed include the first evidence of the existence of CSC, various markers used to identify CSCs, and the findings of several studies based on immunophenotyping of HCCs which showed that 20 to 50% of tumor cells in a HCC express progenitor cell markers such as albumin, CK7 and CK19.

Aims: To correlate the age at surgery, liver function tests, and hepatic and portal tract histo-pathological changes with surgical outcome in the form of disappearance of jaundice in extrahepatic biliary atresia (EHBA). Materials and Methods: This is a retrospective study of 39 cases of EHBA. There were 19 males and 10 females. Kasai's portoenterostomy (KPE) along with liver biopsy was performed in these patients; for purpose of correlation this biopsy was considered to be the preoperative biopsy. These patients were divided into three groups based upon surgical outcome: (A) disappearance of jaundice; (B) initial disappearance of jaundice with recurrence after 3 months; and (C) persistence of jaundice. Postoperatively, liver function tests and liver biopsies were repeated at 3 months after the KPE. Results: There were 11 patients in group A (28%), 21 patients in group B (54%), and seven patients in group C (18%). The age at surgery was comparable in all the three groups. The postoperative levels of serum bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGTP) showed statistically significant improvement as compared with the preoperative levels in group A and B patients. Patients belonging to group C showed no improvement in the liver functions following surgery. The preoperative hepatic histopathological changes (hepatocellular alteration, cholestasis, bile ductular proliferation, and bile duct inflammation) showed a significant difference among the three groups; patients with lesser degrees of pre-existing histopathological changes had better outcome following surgery. Fibrosis was seen in all the three groups preoperatively but the difference was not statistically significant. Group C had significant fibrosis in more than 50% patients. Additional findings, viz. ductal plate malformation (9 patients, 23%) and giant cell transformation (19 patients, 49%) did not show any correlation with surgical outcomes. Conclusions: The liver function tests and the histopathological features appeared to affect the final surgical outcome of these patients. Higher degree of cholestasis, hepatocellular alteration, bile ductule proliferation, bile duct inflammation showed definite correlation with poor surgical outcome. High grade hepatic fibrosis and portal edema showed a trend towards poor outcome but did not achieve statistical significance. [ABSTRACT FROM AUTHOR]

Objective: The Wnt/β-catenin signaling cascade is an important signal transduction pathway in human cancers. Overexpression of β-catenin and its downstream effector, cyclin D1, is implicated in malignant transformation and acquisition of an invasive tumor phenotype. This study aimed to determine the clinical significance of Wnt/β-catenin canonical pathway components in breast cancer. Methods: Expression of β-catenin, disheveled (Dvl) and cyclin D1 was examined in invasive ductal carcinomas (IDCs) of the breast by immunohistochemical analysis. Results: Of the 98 IDCs analyzed, 30% of tumors displayed both nuclear and cytoplasmic staining of Dvl protein, while 52% showed nuclear localization. Loss of cell surface β-catenin was observed in 66% of breast carcinomas, whereas nuclear expression was observed in 48% IDCs. Cyclin D1 overexpression was observed in 60% IDCs; 31/59 (53%) of these tumors showed nuclear expression of β-catenin, suggesting upregulation of the canonical Wnt/β-catenin pathway. Our study demonstrates a significant association between nuclear localization of Dvl and β-catenin (p < 0.01, OR = 15.8). Conclusion: To our knowledge, this is the first study showing an association between nuclear localization of Dvl and β-catenin in IDCs and suggests the upregulation of Wnt/β-catenin pathway components, β-catenin, Dvl and cyclin D1 in IDCs of the breast. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Background Facial massage is an extremely popular form of beauty treatment and is thought to rejuvenate the skin. We decided to study the benefits and untoward effects of this form of facial beauty treatment. Methods One hundred and forty-two women (aged 17–63 years), who had received facial beauty treatment in three well-established beauty parlours in New Delhi, were entered into the study and observed for a period of 12 weeks after the facial beauty treatment. Twenty-seven of the subjects had a repeat facial beauty treatment 4–6 weeks after entry into the study, giving a total of 169 massage episodes observed. Immediate and delayed effects of the beauty treatment were examined. Results Facial beauty treatment generally consists of three steps: vigorous massaging of the face with creams, steaming (using a hot towel or a steaming gadget), and application of a face mask containing adsorbents and astringents. In our study, the creams used for massage included “off the shelf” creams manufactured by standard cosmetic companies in 95 (56.3%) subjects, herbal creams in 61 (36.1%), and creams containing exotic ingredients, such as gold salts, in 13 (7.7%). Sixty-one (36.1%) patients developed erythema and puffiness within 15 min to 2 h after the beauty treatment. This lasted for 2–6 h. Forty-one (24.3%) women underwent the procedure of comedone extraction after steaming. In 12 (7.1%) of these women, persistent erythema was noticed at the site of comedone extraction. Eight (4.7%) women developed mild dermatitis on the face, 2–7 days after the facial beauty treatment. Patch testing with constituents used in the facial beauty treatment was positive in four patients (herbal cream, 1; witch hazel, 1; orange face pack, 1; and gold cream, 1). In 47 (33.1%) subjects, an acneiform eruption was observed 3–10 weeks after the facial beauty treatment (mean, 6.1 ± 3 weeks). Thirteen (27.7%) of these subjects had taken... [ABSTRACT FROM AUTHOR]

AbstractBackground Female patients in the post-adolescent age group presented with predominantly deep-seated nodules and a few comedones situated mainly on the cheeks. As most of these subjects related the onset of their symptoms to antecedent facial beauty treatment, we decided to study the clinical and histologic profile of these patients. Methods Thirty seven subjects (36 women and one man) were questioned in detail about their acneiform eruptions. The patients were examined and a biopsy of typical lesions was taken in eight patients. Results On direct questioning, all patients related the onset of their lesions to facial beauty treatment taken 3–8 weeks previously. The predominant types of lesion were deep-seated nodules, although a few closed comedones were present in some cases. Most lesions took a long time to heal and, on healing, left behind hyperpigmentation. The cheeks were universally involved in all patients, and the chin and forehead were involved in 14. The histopathologic study revealed a predominantly peri-appendageal dermal infiltrate consisting of lymphocytes and histiocytes admixed with polymorphs. A granulomatous infiltrate was seen in one-third of the biopsies. Conclusions This eruption is unlike the earlier eruption described as acne cosmetica in being inflammatory, indolent, and often occurring after the first cream massage itself. [ABSTRACT FROM AUTHOR]

Background: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. Methods: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. Results: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear α-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. Conclusions: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon. [ABSTRACT FROM AUTHOR]

Non-invasive characterization of pancreatic masses aids in the management of pancreatic lesions. Intravoxel incoherent motion-diffusion kurtosis imaging (IVIM-DKI) and machine learning-based texture analysis was used to differentiate pancreatic masses such as pancreatic ductal adenocarcinoma (PDAC), pancreatic neuroendocrine tumor (pNET), solid pseudopapillary epithelial neoplasm (SPEN), and mass-forming chronic pancreatitis (MFCP). A total of forty-eight biopsy-proven patients with pancreatic masses were recruited and classified into pNET (n = 13), MFCP (n = 6), SPEN (n = 4), and PDAC (n = 25) groups. All patients were scanned for IVIM-DKI sequences acquired with 14 b-values (0 to 2500 s/mm2) on a 1.5T MRI. An IVIM-DKI model with a 3D total variation (TV) penalty function was implemented to estimate the precise IVIM-DKI parametric maps. Texture analysis (TA) of the apparent diffusion coefficient (ADC) and IVIM-DKI parametric map was performed and reduced using the chi-square test. These features were fed to an artificial neural network (ANN) for characterization of pancreatic mass subtypes and validated by 5-fold cross-validation. Receiver operator characteristics (ROC) analyses were used to compute the area under curve (AUC). Perfusion fraction (f) was significantly higher (p < 0.05) in pNET than PDAC. The f showed better diagnostic performance for PDAC vs. MFCP with AUC:0.77. Both pseudo-diffusion coefficient (D*) and f for PDAC vs. pNET showed an AUC of 0.73. ADC and diffusion coefficient (D) showed good diagnostic performance for pNET vs. MFCP with AUC: 0.79 and 0.76, respectively. In the TA of PDAC vs. non-PDAC, f and combined IVIM-DKI parameters showed high accuracy ≥ 84.3% and AUC ≥ 0.84. Mean f and combined IVIM-DKI parameters estimated that the IVIM-DKI model with TV texture features has the potential to be helpful in characterizing pancreatic masses. [ABSTRACT FROM AUTHOR]

To evaluate the role of 18FDG-WBPET-CT, Examination under anesthesia (EUA), and multiple-site biopsy in detecting the occult site in head & neck carcinoma of unknown primary (HN-CUP). In this prospective study, 22 patients with diagnosed CUP, after a thorough outpatient endoscopic evaluation of upper airway and radiological evaluation (CT/MRI) that ruled out a primary lesion were included. These patients subsequently underwent whole-body PET-CT and EUA. Based on the presence of suspicious findings (+) or their absence (−) on 18FDG-WBPET-CT (P) and EUA (E), we divided the patients into 5 groups: P−E−, P−E + , P + E−, P + E + , and P + or E +. All these patients underwent bilateral palatine tonsillectomy, bilateral nasopharyngeal biopsy, and ipsilateral lingual tonsillectomy for identification of occult primary. Out of 22 patients, the primary could be detected in 4 patients (18%) after the workup (three in the oropharynx and one in the hypopharynx, all ipsilateral). 18FDG-PET-CT suspected primaries in 7 patients; biopsy was positive for three (sensitivity-75%, specificity-77%, PPV-43%, NPV-93%). Out of 5 patients, who had suspicious findings on EUA, 3 of the biopsies revealed malignancy (sensitivity-75%, specificity-88%, PPV-60%, NPV-94%). Both PET-CT and EUA when combined, yield a NPV of 100% if both are negative and PPV of 100% when both are positive for suspicious findings. No primary was identified in the absence of a suspicion by PET-CT or EUA. Without a suspicion on 18FDG-WBPET-CT and EUA, there is a limited role of multiple-site biopsies in patients of HN-CUP. [ABSTRACT FROM AUTHOR]

Survivin, an inhibitor of apoptosis protein is a biomarker of significance in prognostication of many malignancies. In the current study we investigated the serum survivin levels in patients with oral submucosal fibrosis (OSMF) and squamous cell carcinoma (OSCC). Serum was isolated from, peripheral blood collected of clinically and histopathologically confirmed OSMF and OSCC patients. Circulating level of survivin was measured in patients and control subjects by ELISA and analyzed further using Kruskal–Wallis test and two-sample Wilcoxon rank-sum (Mann–Whitney) test. Serum Survivin levels were significantly reduced in the OSCC group as compared to the control group. No significant correlation was noted between the serum survivin level and various clinicopathological characteristics of OSCC and OSMF patients. Our study suggests that free, wild form of circulating survivin probably has no role in predicting the prognosis of oral cancer or the malignant transformation potential of oral submucosal fibrosis. [ABSTRACT FROM AUTHOR]

Context.--The histologic features in patients with acuteon- chronic liver failure (ACLF) are evolving, and histologic indicators of patients' poor prognosis are not yet fully established. Objective.--To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on coreneedle liver biopsies. Design.--Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory-Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of,.05 was considered significant. Results.--In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P < .001), dense lobular inflammation (P = .03), cholestasis (P < .001), ductular reaction (P = .001), hepatocyte degeneration (P < .001), and absence of advanced fibrosis stages (P < .001) were identified significantly more othen in ACLF patients than in disease controls on univariate analysis. On multivariate Cox regression analysis, the absence of advanced Ishak histologic activity index fibrosis stages (P = .02) and the presence of dense lobular inflammation (P = .04) were associated with increased 28-day mortality in ACLF patients. After adjusting the clinical causes of acute decompensation, only dense lobular inflammation was found as an independent predictor of short-term mortality (P = .04) in ACLF patients. Conclusions.--Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF. [ABSTRACT FROM AUTHOR]

Background: There is limited information on the impact of cytomegalovirus (CMV) infection on clinical outcomes and operative histopathology in children with biliary atresia (BA). We hypothesized that CMV infection is associated with greater histopathological damage and unfavorable short-term clinical outcomes. Materials and Methods: A prospective single-center study was conducted with effect from January 2011–July 2012 including all infants with BA who underwent surgery. Diagnosis of CMV infection was confirmed by serum immunoglobulin M (IgM) positivity or the presence of CMV-deoxyribonucleic acid (DNA) in the liver tissue. Four short-term outcome variables were observed. The cohort was divided into subgroups on the basis of seropositivity (IgM + or IgM−); the presence of CMV-DNA in the liver (polymerase chain reaction [PCR]+ or PCR−); and composite CMV groups (Group 1 – IgM+, PCR+; Group 2 – IgM+, PCR−; Group 3 –- IgM−, PCR+; and Group 4 – IgM−, PCR−). Outcomes and histopathology were compared in these subgroups. Results: A total of 32 infants with BA were operated at a mean age of 3.5 (range: 1–6) months. Serum IgM+ and PCR+ were observed in 50% and 37.5% of the patients. Unfavorable outcomes showed a significant association with IgM+ and not PCR+. Similarly, outcomes were poor for CMV Groups 1 and 2 at 1-month follow-up. Infants with IgM+ and PCR+ showed a greater degree of histopathological damage in terms of bile duct proliferation and severe bile duct fibrosis, respectively. Conclusion: In the present study, there was a high incidence of serum IgM+ (50%) and PCR+ of biopsy specimens (37.5%) in infants with BA. This CMV-infected subgroup was associated with greater histopathological damage and unfavorable short-term outcomes after surgery. [ABSTRACT FROM AUTHOR]

In the present study, we assessed the expression of extracellular matrix (ECM) degrading proteases-cathepsin L and matrix metalloprotease-2 (MMP-2) in pancreatic cancer tissue and correlated their levels with clinicopathological parameters and survival. Both the proteases were expressed in the majority of the tumor tissues examined. Staining intensity of cathepsin L was significantly higher in the tumor stroma compared to tumor epithelium while MMP-2 staining showed no such difference. Both proteases showed correlation with some of the clinicopathological parameters but only cathepsin L expression in tumor epithelium predicted a poor prognosis for the disease. [ABSTRACT FROM AUTHOR]

Transcriptome‐based drug screening is emerging as a powerful tool to identify geroprotective compounds to intervene in age‐related disease. We hypothesized that, by mimicking the transcriptional signature of the highly conserved longevity intervention of FOXO3 (daf‐16 in worms) overexpression, we could identify and repurpose compounds with similar downstream effects to increase longevity. Our in silico screen, utilizing the LINCS transcriptome database of genetic and compound interventions, identified several FDA‐approved compounds that activate FOXO downstream targets in mammalian cells. These included the neuromuscular blocker atracurium, which also robustly extends both lifespan and healthspan in Caenorhabditis elegans. This longevity is dependent on both daf‐16 signaling and inhibition of the neuromuscular acetylcholine receptor subunit unc‐38. We found unc‐38 RNAi to improve healthspan, lifespan, and stimulate DAF‐16 nuclear localization, similar to atracurium treatment. Finally, using RNA‐seq transcriptomics, we identify atracurium activation of DAF‐16 downstream effectors. Together, these data demonstrate the capacity to mimic genetic lifespan interventions with drugs, and in doing so, reveal that the neuromuscular acetylcholine receptor regulates the highly conserved FOXO/DAF‐16 longevity pathway. [ABSTRACT FROM AUTHOR]

Thirty patients with breast cancer were prospectively randomized into case and control groups receiving 40 mg famotidine preoperatively for 10-14 days and routine premedication, respectively. Surgical specimens were evaluated objectively for tumor infiltrating lymphocytes in the center and in the periphery of the tumor along with evaluation of metastatic lymph nodes for reactive changes. Ten famotidine-treated cases (67%) showed significant lymphocytic infiltration in the center compared to 4 controls (27%) (p =0.03). Eleven cases (77%) had significant lymphocytic infiltration in the periphery (p =0.03) compared to 5 controls (33%). Considering both sites, lymphocytic response was significant in 9 (60%) cases as opposed to only 3 (20%) controls (p =0.03). This response did not correlate with the stage, grade of tumor or menopausal status of patients in either group. Seventy-eight percent (78%) of the cases showed significant reactive changes in the metastatic lymph nodes as compared to 22% in controls (p <0.01). This study suggests that famotidine enhances tumor infiltrating lymphocytes in breast cancer and might have potential as an immunomodulator. A larger confirmatory study is suggested. [ABSTRACT FROM AUTHOR]

Despite preclinical success, monotherapies targeting EGFR or cyclin D1-CDK4/6 in Head and Neck squamous cell carcinoma (HNSCC) have shown a limited clinical outcome. Here, we aimed to determine the combined effect of palbociclib (CDK4/6) and afatinib (panEGFR) inhibitors as an effective strategy to target HNSCC. Using TCGA-HNSCC co-expression analysis, we found that patients with high EGFR and cyclin D1 expression showed enrichment of gene clusters associated with cell-growth, glycolysis, and epithelial to mesenchymal transition processes. Phosphorylated S6 (p-S6), a downstream effector of EGFR and cyclin D1-CDK4/6 signalling, showed a progressive increase from normal oral tissues to leukoplakia and frank malignancy, and associated with poor outcome of the patients. This increased p-S6 expression was drastically reduced after combination treatment with afatinib and palbociclib in the cell lines and mouse models, suggesting its utiliy as a prognostic marker in HNSCC. Combination treatment also reduced the cell growth and induced cell senescence via increasing reactive oxygen species with concurrent ablation of glycolytic and tricarboxylic acid cycle intermediates. Finally, our findings in sub-cutaneous and genetically engineered mouse model (K14-CreERtam;LSL-KrasG12D/+;Trp53R172H/+) studies showed a significant reduction in the tumor growth and delayed tumor progression after combination treatment. This study collectively demonstrates that dual targeting may be a critical therapeutic strategy in blocking tumor progression via inducing metabolic alteration and warrants clinical evaluation. [ABSTRACT FROM AUTHOR]

Objective To examine Juvenile Angiofibroma (JA) tissue for expression of vascular endothelial growth factor (VEGF), and to explore its relationship with puberty status, stage, recurrence and the intraoperative blood loss. Methods Retrospective cohort study of 36 histologically proven cases of JA. Minimum follow up period was 3 years. VEGF expression on tumor cells assessed by immunohistochemistry and graded on two criteria – percentage of cells expressing positivity and the intensity of positivity. These two parameters assessed for impact on puberty status, stage, recurrence, and blood loss. Results VEGF expression noted on the tumor endothelial cells in 36/36, and on the tumor stromal cells in 34/36. The percentage of cells expressing VEGF and the intensity of expression were not significantly related to puberty status, tumor stage, recurrence, or intra-operative blood loss ( p values 0.3–1.0). Conclusion VEGF expression is near universal in JA. Such expression is independent of puberty status and stage, and does not impact on intra operative blood loss and recurrence. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug–induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document. [ABSTRACT FROM AUTHOR]

Background and Aim: Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) that requires duodenal biopsies. There is a need for non‐invasive biomarker(s) that can predict the presence of villous abnormalities. Methods: Levels of plasma citrulline, plasma intestinal fatty acid binding protein (I‐FABP), and serum regenerating gene 1α (Reg1α) were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern were validated in a predicted model of enteropathy. Optimum diagnostic cut‐off values were derived, and the results were further validated in a prospective validation cohort. Results: While level of plasma citrulline was significantly lower, the levels of plasma I‐FABP and serum Reg1α were significantly higher in patients with CeD (n = 131) in comparison with healthy (n = 216) and disease controls (n = 133), and their levels reversed after a gluten‐free diet (GFD). In the model of predicted enteropathy (n = 70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I‐FABP and Reg1α. The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was ≤ 30 μM/L and I‐FABP levels were ≥ 1100 pg/mL, respectively. The results were validated in a prospective validation cohort (n = 104) with a sensitivity and specificity of 79.5% and 83.1%, respectively, for predicting villous abnormalities of modified Marsh grade > 2 at calculated cut‐off values of citrulline and I‐FABP. Conclusions: Plasma citrulline ≤ 30 μM/L is the most consistent, highly reproducible non‐invasive biomarker that can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations. [ABSTRACT FROM AUTHOR]

Background/Aims: The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies. Methods: We performed a computerassisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists. Results: Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%-85.03%) and interobserver (24.6%-71.5%) agreements. Conclusions: Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD. [ABSTRACT FROM AUTHOR]

Background and Aim: While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS. Methods: Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis. Results: Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D‐xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia. Conclusions: Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests. [ABSTRACT FROM AUTHOR]

Background Histological assessment of dysplasia in Barrett’s esophagus (BE) has high inter-observer variability. Hence, use of ancillary markers for early detection of dysplasia in BE is an important clinical question. Methods In this retrospective study consecutive cases of BE (n = 59), over a period of 4 years were included. Hematoxylin and eosin stained sections were reviewed independently by 3 senior qualified pathologists, who graded the dysplasia according to the Vienna Classification system and inter-observer agreement was analysed using the Kappa statistics. Subsequently Alpha-Methyl Acyl-CoA Racemase (AMACR), p53, CyclinD1, β-catenin, H2AX and M30 immunohistochemical (IHC) stains were examined on the following disease categories: BE with no dysplasia [NFD] (45), BE with indefinite for dysplasia (IFD) (4), low grade dysplasia (LGD) (3), high grade dysplasia (HGD) (2) and in adenocarcinomas (5). H score was calculated by adding up products of different grades of stain distribution and stain intensities (range of scores 0–300). Results Among the 3 pathologists, overall agreement was poor (k 0.06; 95% CI −0.089 to 0.145), with highest disagreement noted for differentiating the LGD and IFDs (k = 0.21). After revising the histological criteria, the kappa improved to 0.53. Among the IHC stains performed, p53, β-catenin, H2AX and M30 stains were significantly useful to differentiate between IFD and LGD ( P values: 0.04, 0.004, 0.05 & 0.04, respectively). AMACR and β-catenin stains though were up-regulated in HGD/adenocarcinomas than in other categories, their expression were not statistically different between the IFD and LGDs. Conclusions A detail histological scoring system may bring uniformity in histological interpretation of dysplasia in BE. Using a combined panel of IHC stains seems helpful in detection of dysplasia in BE, especially to differentiate the IFD and LGD changes in BE. [ABSTRACT FROM AUTHOR]

Background/Aims: Classical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB). Methods: Colonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1ϕ marker) and CD163/CD68 (an M2ϕ marker), and the ratio of M1ϕ to M2ϕ was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment. Results: M1ϕ polarization was more prominent in CD biopsies (P =0.002) than in iTB (P =0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1ϕ predominance was significant (P =0.001). In iTB, the densities of M1ϕ did not differ between granuloma-positive and granuloma-negative biopsies (P =0.1). Interestingly, higher M1ϕ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients. Conclusions: Proinflammatory M1ϕ polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD. [ABSTRACT FROM AUTHOR]

Aim: This study investigates the fall in total serum bilirubin levels within 1 week after surgery, as a marker to predict early outcome in biliary atresia (BA) patients post-Kasai portoenterostomy (KP). Methods: The ratio of total serum bilirubin levels at the 7th postoperative day to the preoperative level (TB7/TB0) in patients undergoing KP was calculated (January 2011-July 2015). Patients were stratified after 3-months follow-up into outcome groups depending on the clinical clearance of jaundice and TB7/TB0 ratio was correlated to outcome and liver histopathological changes in these groups. Results: Sixty-one patients (M:F = 44:17), median age 75 days were included. At the end of 3 months, 27 (44.39%) were anicteric while 26 (42.6%) were still clinically jaundiced. Patients with a higher median value of TB7/TB0, that is, 0.856 were more likely to have jaundice at the end of 3 months as compared to patients with a lower median value of 0.615 (P < 0.0001). A cutoff TB7/TB0 ratio >0.723 predicted the KP outcome with 84.6% sensitivity and 81.5% specificity. The difference in TB7/TB0 ratio between patients with varying severity of liver histopathological changes was also significant, namely, cholestasis (P = 0.01), hepatocellular damage (P = 0.03), portal inflammation (P = 0.04), and portal fibrosis (P = 0.02). Conclusions: The rapidity of fall in the total serum bilirubin levels within 1 week post-KP was able to predict the likely outcome in BA patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Aberrant crypt foci (ACF) are early microscopic lesions of the colonic mucosa, which can be detected by magnified chromoendoscopy. Herein, we have investigated whether ACF identified in different clinical groups can be differentiated based on their characteristics. Methods: Macroscopically unremarkable mucosal flaps were collected from 270 fresh colectomies and divided into 3 clinical groups: colorectal carcinoma (group A), disease controls having known pre-neoplastic potential (group Bc), and disease controls without risk of carcinoma development (group Bn). Topographic and histologic analysis, immunohistochemistry, and molecular studies (high-resolution melt curve analysis, real-time polymerase chain reaction, and Sanger sequencing) were conducted for certain neoplasia-associated markers. Results: ACF were seen in 107 cases, out of which 72 were left colonic ACF and 35 right colonic ACF (67.2% vs. 32.7%, P =0.02). The overall density of left colonic ACF was 0.97/cm, which was greater than the right colonic ACF density of 0.81/cm. Hypercrinia was present in 41 out of 72 left colonic ACF and in 14 out of 35 right colonic ACF (P =0.01). Immunohistochemical expression of p53 was also greater in left colonic ACF than in right colonic ACF (60.5% vs. 38.2%, P =0.03). However, ACF identified among the 3 clinical groups did not show any distinguishing topographic, histological, or genetic changes. Conclusions: Left colonic ACF appear to be high-risk based on their morphological and prototypic tumor marker signature. ACF identified in different clinical groups do not show significant genotypic or topographic differences. Further detailed genetic studies are required to elucidate them further. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic accuracy of shear wave elastography (SWE) and transient elastography (TE) in the evaluation of liver fibrosis in chronic hepatitis B (CHB) and C (CHC) patients taking liver biopsy as gold standard. Methods: Ethics committee approved this prospective cross-sectional study. Between October 2012 and December 2014, consecutive CHB/CHC patients fulfilling the inclusion criteria were included-age more than 18 years, informed written consent, willing and suitable for liver biopsy. SWE, TE, and biopsy were performed the same day. Liver stiffness measurement (LSM) cut-offs for various stages of fibrosis were generated for SWE and TE. AUC, sensitivity, specificity, and positive/negative predictive values were estimated individually or in combination. Results: CH patients ( n = 240, CHB 172, CHC 68), 176 males, 64 females, mean age 32.6 ± 11.6 years were enrolled. Mean LSM of patients with no histological fibrosis (F0) was 5.0 ± 0.7 and 5.1+1.4 kPa on SWE and TE, respectively. For differentiating F2 and F3-4 fibrosis on SWE, at 7.0 kPa cut-off, the sensitivity was 81.3% and specificity 77.6%. For TE, at 8.3 kPa cut-off, sensitivity was 81.8% and specificity 83.1%. For F3 vs. F4, SWE sensitivity was 83.3% and specificity 90.7%. At 14.8 kPa cut-off, TE showed similar sensitivity (83.3%) but specificity increased to 96.5%. Significant correlation between SWE and TE was observed ( r = 0.33, p < 0.001). On combining SWE and TE, a drop in sensitivity with increased specificity for all stages of liver fibrosis occured. Conclusion: SWE is an accurate technique for evaluating liver fibrosis. SWE compares favorably with TE especially for predicting advanced fibrosis/cirrhosis. Combining SWE and TE further improves specificity. [ABSTRACT FROM AUTHOR]

Background and Aim The literature on possible factors that could trigger a relapse in patients with ulcerative colitis (UC) in clinical, endoscopic, and histological remission on long-term follow up is scarce. To determine the relapse rate in patients with UC in clinical, endoscopic, and histological remission and identify factors that may influence the risk of relapse. Methods Patients with UC in clinical, endoscopic, and histological remission were enrolled between January and July 2010 and followed up for 1 year to determine the effect of clinical, dietary, and psychological factors on relapse. Information regarding factors that may affect relapse such as infection, antibiotic, or non-steroidal anti-inflammatory drugs (NSAIDs) use and any other factor that the patient felt important and compliance with medications was obtained. Results Ninety-seven patients (59 males, mean age 39 ± 11.9 years) were followed up for a mean duration of 9 ± 2.3 months. Eighteen (18.6%) relapsed with the median time to relapse being 3.5 months. On univariate analysis, more relapsers had significantly higher NSAIDs use within 15 days of relapse, respiratory tract infection within 4 weeks, use of steroids more than once in past, higher consumption of calcium, riboflavin, and vitamin A, and lower consumption of sugars. On multivariate analysis, NSAIDs use (HR [95% CI]: 6.41 [1.88-21.9]) and intake of vitamin A (HR [95% CI]: 1.008 [1.000-1.016]) were statistically significant predictors of relapse. Conclusion With a relapse rate of 18.6% over a follow up of 9 months in patients with UC in clinical, endoscopic, and histological remission, independent predictors of relapse were history of NSAIDs use within 15 days of relapse and higher intake of vitamin A. [ABSTRACT FROM AUTHOR]

Purpose This study aims to determine the pre-biopsy diffusion-weighted imaging (DWI) and magnetic resonance spectroscopic imaging (MRSI) characteristics of patients with high-grade prostatic intraepithelial neoplasia (HGPIN) and perform follow-up studies in these patients to assess the clinical implications. Materials and methods One hundred sixteen men with prostate specific antigen between 4 and 10 ng/ml underwent pre-biopsy MR examinations. Nine of them had HGPIN lesions without concomitant prostate cancer (PCa) on biopsy. Apparent diffusion coefficient (ADC) and metabolite ratio [Citrate/(Choline + Creatine)] were calculated and these 9 patients were followed to determine the clinical outcomes. Results Mean ADC for HGPIN foci was 1.01 ± 0.16 × 10 − 3 mm 2 /s while for the normal peripheral zone it was 1.69 ± 0.25 × 10 − 3 mm 2 /s (p < 0.005). Mean metabolite ratio for voxels in the HGPIN region of initial biopsy was 0.24 ± 0.16 while for the normal peripheral zone the value was 2.66 ± 1.57 (p < 0.005). Four of 5 patients who were available for follow-up were detected to have prostate cancer on repeat biopsy. No significant change in metabolite ratio and PSA was observed while ADC showed further reduction on follow-up. Conclusion HGPIN foci have ADC and metabolite ratio values similar to adenocarcinoma prostate, indicating that such patients have a high likelihood of developing cancer. DWI may help identify such men who may be candidates for close follow-up. [ABSTRACT FROM AUTHOR]

Background Patients with idiopathic hypoparathyroidism (IH) require variable doses of calcium and 1-α-(OH)D. The reasons for such variability are not clear. As autoimmune mechanisms may play a role in IH, there is a possibility of coexistent coeliac disease with calcium/vitamin D malabsorption. Objective We assessed the prevalence of coeliac disease and antitissue transglutaminase autoantibodies (anti-tTGAbs) in IH and analysed the effect of a gluten-free diet on calcaemic control. Method A total of 171 patients with IH and 126 healthy controls were screened for anti-tTGAb. IH patients with anti-tTGAb >20 RU/ml underwent duodenoscopy and intestinal biopsy; those with biopsy-proven coeliac disease were followed up on a gluten-free diet. Results Eleven of 171 (6·4%) patients with IH and seven of 126 (5·6%) controls had anti-tTGAb ( P = 0·81). There was no difference in the clinical and biochemical parameters at diagnosis and during long-term follow-up of 7·2 ± 4·8 year (mean serum total calcium = 1·88 ± 0·16 vs 1·82 ± 0·36 mmol/l, P = 0·52; phosphorus = 1·81 ± 0·17 vs 1·87 ± 0·36 mmol/l, P = 0·53) in IH patients with and without anti-tTGAb. Although CaSRAb positivity was comparable in the two groups, IH patients with anti-tTGAb had higher TPOAb positivity (45·5% vs 12·8%, P = 0·02). Coeliac disease was diagnosed in only 2/9 patients with IH on biopsy, both of whom showed improved calcaemic control with a gluten-free diet. Conclusion The prevalence of coeliac autoimmunity (6·4%) and coeliac disease (1·2%) in patients with IH seems to be similar to that in the general population. Notwithstanding this modest prevalence, it is important to be aware of the potential occurrence of coeliac disease with IH and the beneficial effect of a gluten-free diet on calcium control. [ABSTRACT FROM AUTHOR]

Background and Aim: Acute on chronic liver failure (ACLF) because of precipitating factors (variceal bleed/infections) identifies cirrhotics at risk for high short-term mortality. Information on ACLF because of acute hepatic insults is lacking. The aim of the study was to evaluate acute hepatic insults in ACLF and their effect on the course and outcome. Methods: In a prospective study, 213 consecutive patients of ACLF because of acute hepatic insults were included. Etiology of acute hepatic insult, frequency of silent, and overt chronic liver disease (CLD), organ failure (OF), and outcomes were assessed. Prognostic models such as model for endstage liver disease (MELD), acute physiology and chronic health evaluation (APACHE II), and chronic liver failure-sequential organ failure (CLIF-SOFA) were evaluated. Results: Etiologies of acute hepatic insult were hepatitis virus(es)- 81 (38%; HBV-42, HEV-39), continuous alcohol consumption-77 (33.3%), antituberculosis drugs-11 (5.2%), autoimmune hepatitis flare-5(2.3%), cryptogenic-44 (20.7%). The common causes of CLD were alcohol ( n = 85/40%), HBV( n = 52/24%), and cryptogenic( n = 50/20%). The MELD, APACHE II, and CLIF-SOFA scores were similar among silent and overt CLD and did not influence outcome. Predominant etiologies of ACLF were hepatitis virus(es) reactivation or superinfection in silent CLD(52/112, 46.4%) and alcohol among overt CLD(43/101, 43%). Independent predictors of mortality included hepatic-encephalopathy (early, HR: 4.01; advanced, HR: 6.10), serum creatinine ≥1.5 mg/dl (HR: 4.53), CLIF-SOFA ≥8(HR: 1.69), and etiology of acute hepatic insult (alcohol, HR: 4.08; cryptogenic, HR: 3.18). HEV-ACLF had lower mortality (12.8% vs. 33-54% in other etiologies; P < 0.001). OF was major determinant of mortality. With increasing number of OF, mortality increased linearly( P = 0.001). Conclusions: Hepatitis virus(es) and continuous alcohol consumption are important causes of ACLF caused by acute hepatic insults. HEV-ACLF has lower mortality. OF is an important prognostic predictor. [ABSTRACT FROM AUTHOR]

Objective: This study focused on whether primary cultures of ovarian cancer (OC) cells established from ascites can be used to evaluate response to chemotherapeutic agents and if curcumin could enhance the efficacy of these agents.Materials and Methods: We established five primary cultures of ascitic cells from OC patients and treated them with curcumin, carboplatin, and paclitaxel singly and in combinations. The percentage of apoptotic cells was determined by flow cytometry.Results: There was a wide variation in the response of individual primary cultures to treatment with the chemotherapeutic agents. Curcumin by itself was as good as carboplatin or paclitaxel in inducing apoptosis in the primary OC cells. Curcumin was not able to affect the carboplatin mediated cell killing. However, a combination of curcumin and paclitaxel was additive and was equally effective as a combination of carboplatin and paclitaxel. A combination of curcumin carboplatin, and paclitaxel was also found to be additive and, in fact, turned out to be the best combination that gave the highest percentage of apoptosis in vitro.Conclusion: This study highlights the fact that primary cultures of OC cells can be used to detect response to chemotherapeutic agents and help to individualize the treatment offered to OC patients. [ABSTRACT FROM AUTHOR]

Background & objectives: Standard of care for chronic hepatitis C (CHC) in India is peginterferon and ribavirin (RBV). The response to treatment in real life stetting is unclear. The objectives of this study were to evaluate the demographic profile and assess the virological response and predictors of response in CHC patients. Methods: Consecutive patients with CHC were included in this study. Detailed clinical history, risk factors, and predictive factors of response were noted. Patients were treated with peginterferon α2b (1.5 μg/kg/wk) and RBV (12 mg/kg/day) for 6 to 18 months based on response. Results: A total of 211 patients were included in the analysis, mean age 40.6±12.3 yr, 144 (68%) were males and 71 (34%) had compensated cirrhosis. Commonest risk factor for acquiring CHC was previous transfusion and surgery (51%). Genotype 3 (72%) was most common followed by genotype 1 (23%). Overall sustained virologic response (SVR) was 64 per cent [95% CI 57.1%-70.4%]. The SVR was 66.5 per cent [95% CI 58.34-73.89%] for genotype 3 and 61.2 per cent [95% CI 46.23 to 74.80%] for genotype 1. Non-cirrhotics had better SVR rates compared to cirrhotics (76 vs 41%, P<0.001). On multivariate analysis, BMI ≥23 kg/m2, HOMA-IR ≥2, compliance (≤80%), and fibrosis >2 were predictors of low SVR. Interpretation & conclusions: Genotype 3 was the commonest HCV genotype. The commonest source of infection was previous transfusion and surgery. SVR rates for genotypes 3 were better than genotype 1 patients. Predictors of non-response were high BMI, insulin resistance, significant fibrosis and inadequate compliance. [ABSTRACT FROM AUTHOR]