Tunable 2D Conjugated Porous Organic Polymer Films for Precise Molecular Nanofiltration and Optoelectronics.

Structural design of 2D conjugated porous organic polymer films (2D CPOPs), by tuning linkage chemistries and pore sizes, provides great adaptability for various applications, including membrane separation. Here, four free-standing 2D CPOP films of imine- or hydrazone-linked polymers (ILP/HLP) in combination with benzene (B-ILP/HLP) and triphenylbenzene (TPB-ILP/HLP) aromatic cores are synthesized. The anisotropic disordered films, composed of polymeric layered structures, can be exfoliated into ultrathin 2D-nanosheets with layer-dependent electrical properties. The bulk CPOP films exhibit structure-dependent optical properties, triboelectric nanogenerator output, and robust mechanical properties, rivaling previously reported 2D polymers and porous materials. The exfoliation energies of the 2D CPOPs and their mechanical behavior at the molecular level are investigated using density function theory (DFT) and molecular dynamics (MD) simulations, respectively. Exploiting the structural tunability, the comparative organic solvent nanofiltration (OSN) performance of six membranes having different pore sizes and linkages to yield valuable trends in molecular weight selectivity is investigated. Interestingly, the OSN performances follow the predicted transport modeling values based on theoretical pore size calculations, signifying the existence of permanent porosity in these materials. The membranes exhibit excellent stability in organic solvents at high pressures devoid of any structural deformations, revealing their potential in practical OSN applications.

Recent advances in BCRP-induced breast cancer resistance treatment with marine-based natural products.

Breast cancer is the prominent cause of cancer-related death in women globally in terms of incidence and mortality. Despite, recent advances in the management of breast cancer, there are still a lot of cases of resistance to medicines, which is currently one of the biggest problems faced by researchers across the globe. Out of several mechanisms, breast cancer resistance protein (BCRP) arbitrated drug resistance is a major concern. Hormonal, cytotoxic and immunotherapeutic drugs are used in the systemic therapy of breast cancer. It is vital to choose drugs based on the clinical and molecular attributes of the tumor to provide better treatment with greater efficacy and minimal harm. Given the aforementioned necessity, the use of marine flora in treating breast cancer cannot be neglected. The scientists also stressed the value of marine-derived goods in avoiding breast cancer resistance. Future research into the identification of anticancer drugs will heavily draw upon the marine environment's ample supply of marine-derived natural products (MNPs), which have a wide range of biological functions. Cell cycle arrest, induction of apoptosis and anti-angiogenic, anti-proliferative and anti-metastasis actions are all part of their processes. The overview of breast cancer, the mechanisms underlying its resistance, recent clinical trials based on marine-derived products in breast cancer and the use of marine products in the treatment of breast cancer are highlighted in this paper. Moreover, the authors also emphasised the importance of marine-derived products in preventing breast cancer resistance.

A correlation between oxidative stress and diabetic retinopathy: An updated review.

Oxidative stress (OS) is a cytopathic outcome of excessively generated reactive oxygen species (ROS), down regulated antioxidant defense signaling pathways, and the imbalance between the produced radicals and their clearance. It plays a role in the genesis of several illnesses, especially hyperglycemia and its effects. Diabetic retinal illness, a micro vascular side effect of the condition, is the prime reason of diabetic related blindness. The OS (directly or indirectly) is associated with diabetic retinopathy (DR) and related consequences. The OS is responsible to induce and interfere the metabolic signaling pathways to enhance influx of the polyol cascades and hexosamine pathways, stimulate Protein Kinase-C (PKC) variants, and accumulate advanced glycation end products (AGEs). Additionally, the inequity between the scavenging and generation of ROS is caused by the epigenetic alteration caused by hyperglycemia that suppresses the antioxidant defense system. Induced by an excessive buildup of ROS, retinal changes in structure and function include mitochondrial damage, cellular death, inflammation, and lipid peroxidation. Therefore, it is crucial to comprehend and clarify the mechanisms connected to oxidative stress that underlie the development of DR.

Current State and Opportunities with Long-acting Injectables: Industry Perspectives from the Innovation and Quality Consortium "Long-Acting Injectables" Working Group.

Long-acting injectable (LAI) formulations can provide several advantages over the more traditional oral formulation as drug product opportunities. LAI formulations can achieve sustained drug release for extended periods of time, which results in less frequent dosing requirements leading to higher patient adherence and more optimal therapeutic outcomes. This review article will provide an industry perspective on the development and associated challenges of long-acting injectable formulations. The LAIs described herein include polymer-based formulations, oil-based formulations, and crystalline drug suspensions. The review discusses manufacturing processes, including quality controls, considerations of the Active Pharmaceutical Ingredient (API), biopharmaceutical properties and clinical requirements pertaining to LAI technology selection, and characterization of LAIs through in vitro, in vivo and in silico approaches. Lastly, the article includes a discussion around the current lack of suitable compendial and biorelevant in vitro models for the evaluation of LAIs and its subsequent impact on LAI product development and approval.

Phenothiazine functionalized fulleropyrrolidines: synthesis, charge transport and applications to organic solar cells.

A series of phenothiazine-C60/70 dyads containing fulleropyrrolidine tethered to C-3 position (C60-PTZ and C70-PTZ) or to the heteroatom N-position via either phenyl (C60-Ph-PTZ and C70-Ph-PTZ) or phenoxyethyl linkers (C60-PhOEt-PTZ and C70-PhOEt-PTZ) of the phenothiazine were synthesized and light-induced electron transfer events were explored. Optimized studies suggested that the highest molecular orbital (HOMO) resides on donor phenothiazine moiety while lowest molecular orbital (LUMO) on the acceptor fulleropyrrolidine moiety of the dyads. Optical and electrochemical properties suggested no electronic communication between the donor and acceptor moieties in the ground state. However, steady-state emission studies in solvents of varied polarity, involving selective excitation of C60/C70, disclosed that the emission intensity of C60/C70 was quenched in the dyads in the increasing order, C60/70-PTZ > C60/70-Ph-PTZ > C60/70-PhOEt-PTZ as a consequence of the donor-acceptor distance resulted due to spacer lengths. Also, the emission quenching is more pronounced in polar solvents such as DMF compared to a non-polar solvent, toluene. With the support of parallel electrochemical studies, the emission quenching is attributed to intramolecular photo-induced electron transfer occurring from PTZ to (C60/C70)* generating a radical ion pair, PTZ+⋅-C60-⋅/PTZ+⋅-C70-⋅. Finally, bulk heterojunction (BHJ) solar cells devices inverted fashion prepared by employing the dyads as acceptors, and PTB7 as donor, suggested that the devices prepared from C70 derivatives i.e., PTB7:C70-PTZ and PTB7:C70-PhOEt-PTZ exhibited better power conversion efficiency of 2.66% and 2.15%, respectively over C60 derivatives i.e., PTB7:C60-PTZ and PTB7:C60-PhOEt-PTZ with the efficiencies of 1.80 and 1.72%, respectively. AFM studies revealed that the poor performance of PTB7:C60-PTZ- and PTB7:C60-PhOEt-PTZ-based devices can be ascribed to the lower solubility of the dyads in 1,2-DCB solvent leading to rough morphology.

Generation and validation of structurally defined antibody-siRNA conjugates.

Gene silencing by RNA interference (RNAi) has emerged as a powerful treatment strategy across a potentially broad range of diseases. Tailoring siRNAs to silence genes vital for cancer cell growth and function could be an effective treatment, but there are several challenges which must be overcome to enable their use as a therapeutic modality, among which efficient and selective delivery to cancer cells remains paramount. Attempts to use antibodies for siRNA delivery have been reported but these strategies use either nonspecific conjugation resulting in mixtures, or site-specific methods that require multiple steps, introduction of mutations, or use of enzymes. Here, we report a method to generate antibody-siRNA (1:2) conjugates (ARCs) that are structurally defined and easy to assemble. This ARC platform is based on engineered dual variable domain (DVD) antibodies containing a natural uniquely reactive lysine residue for site-specific conjugation to ß-lactam linker-functionalized siRNA. The conjugation is efficient, does not compromise the affinity of the parental antibody, and utilizes chemically stabilized siRNA. For proof-of-concept, we generated DVD-ARCs targeting various cell surface antigens on multiple myeloma cells for the selective delivery of siRNA targeting ß-catenin (CTNNB1). A set of BCMA-targeting DVD-ARCs at concentrations as low as 10 nM revealed significant CTNNB1 mRNA and protein knockdown.

Giant coronary aneurysms in an infant: Dilemma of MIS-C.

COVID-19 related multisystem inflammatory syndrome in children (MIS-C) can present with cardiovascular complications like shock, arrhythmias, pericardial effusion, and coronary artery dilatation. The majority of MIS-C associated coronary artery abnormalities are dilation or small aneurysms which are transient and resolve in a few weeks. We present here a case of a 3-month-old child who was noted to have giant aneurysms of her coronary arteries (LAD and RCA) 26 days after testing positive for COVID-19. She was treated with IVIG, infliximab, and glucocorticoids along with aspirin, clopidogrel, and enoxaparin. She did not show any signs of coronary ischemia or cardiac dysfunction but continued to have persistent giant coronary artery aneurysms involving the LAD (z-score ∼35) and RCA (z-score ∼30). This study emphasizes the importance of early detection and aggressive management of MIS-C to prevent potentially life-threatening consequences.

Establishment of Myocardial Strain Measurement Data in Pediatric Patients Without Structural Heart Disease: A Single Center Study.

Accurate assessment of LV systolic function remains a challenge, especially in the pediatric population. Myocardial strain measurement by 2D speckle tracking echocardiography (2DSTE) is a relatively new modality for assessment of regional and global myocardial wall motion. This study aims to establish the normative value among various pediatric age groups at a large pediatric tertiary care institution and to describe the challenges encountered in establishing such strain data. Transthoracic echocardiograms were acquired in 121 healthy children (age 0-21 years) and were retrospectively analyzed. The global longitudinal strain (GLS) was obtained by 2D speckle tracking using Philips Epiq7® and QLAB post processing software. The normative value for left ventricular GLS (%) obtained in our study was - 20.8 ± 2.3 (< 1 year); - 21.4 ± 2.2 (1-4 years); - 19.6 ± 2.4 (5-9 years); - 19.4 ± 2.6 (10-14 years); - 18.9 ± 3.0 (15-21 years). There was a statistically significant difference in GLS between the different age groups. The BMI (kg/m2) of assessed subjects were 14.6 ± 2.3 (< 1 year); 16.3 ± 1.5 (1-4 years); 16.7 ± 2.3 (5-9 years); 21.3 ± 4.6 (10-14 years); 23.9 ± 5.9 (15-21 years). There was no significant difference in GLS by gender or by BMI found in our study. We present our experience with establishment of normative values of 2DSTE in our pediatric echocardiography lab. This study shows that age is the major determinant of variation in peak GLS in healthy subjects, emphasizing the importance of establishment of normative data among various age groups in pediatrics.

Does myocardial strain remain abnormal long after normalization of ejection fraction in patients with acute myocarditis?

Myocarditis is a common cause for acute heart failure in the pediatric population. Various imaging modalities have evolved over the past 3 decades in order to noninvasively image the myocardium in this patient population. These include standard 2-dimensional echocardiographic imaging, tissue Doppler imaging, and magnetic resonance imaging of the heart. More recently, myocardial speckle tracking also known as strain imaging has been utilized to assess regional wall motion abnormalities with increasing accuracy. We report a case of acute myocarditis in a teenage female in whom progression of myocardial strain findings correlated with the rapidly evolving clinical course of the patient.

Photobiomodulation Alleviates Postoperative Discomfort After Mandibular Third Molar Surgery.

PURPOSE: Surgical removal of mandibular third molars is associated with some degree of postoperative pain, trismus, and facial swelling. The purpose of the study was to evaluate the effect of photobiomodulation in reducing these postoperative side effects after surgical removal of mandibular third molars. MATERIALS AND METHODS: This randomized, double-blinded, split-mouth pilot study was carried out in the Department of Oral and Maxillofacial Surgery, Post Graduate Institute of Dental Sciences, Rohtak, India, among patients with impacted mandibular third molars. In each patient, 1 side was treated by photobiomodulation and the other side received placebo. Photobiomodulation was performed by intraoral and extraoral application of an 830-nm and 30-mW laser at different time points. Pain, trismus, and facial swelling were evaluated at all time points. The number of analgesics taken also was recorded. The data were analyzed using descriptive, bivariate and multivariate statistics. RESULTS: The study was conducted in 25 patients (56% male patients) with a mean age of 22.16 ± 4.60 years. There were 50 sites divided equally into both groups. The sites treated with photobiomodulation showed a significant reduction in pain and swelling (P < .05) compared with the sites in the placebo group. Moreover, an increase in mouth opening was noted after photobiomodulation compared with that in the placebo group, but this was not statistically significant (P > .05). CONCLUSIONS: The results of this study suggest that photobiomodulation is effective in reducing pain and swelling after mandibular third molar surgery. Hence, it can be used as an alternative and effective modality after surgical removal of mandibular third molars, thereby improving the quality of life of the patients.

Emerging trends in the prenatal diagnosis of complex CHD and its influence on infant mortality in this cohort.

BACKGROUND: Fetal echocardiography is the main modality of prenatal diagnosis of CHD. This study was done to describe the trends and benefits associated with prenatal diagnosis of complex CHD at a tertiary care centre. METHODS: Retrospective chart review of patients with complex CHD over an 18-year period was performed. Rates of prenatal detection along with early and late infant mortality outcomes were studied. RESULTS: Of 381 complex CHD patients born during the study period, 68.8% were diagnosed prenatally. Prenatal detection rate increased during the study period from low-50s in the first quarter to mid-80s in the last quarter (p=0.001). Rate of detection of conotruncal anomalies increased over the study period. No infant mortality benefit was noted with prenatal detection. CONCLUSIONS: Improved obstetrical screening indications and techniques have contributed to higher proportions of prenatal diagnosis of complex CHD. However, prenatal diagnosis did not confer survival benefits in infancy in our study.

Elucidation of the Cryptic Methyl Group Epimerase Activity of Dehydratase Domains from Modular Polyketide Synthases Using a Tandem Modules Epimerase Assay.

Dehydratase (DH) domains of cryptic function are often found in polyketide synthase (PKS) modules that produce epimerized (2S)-2-methyl-3-ketoacyl-ACP (acyl carrier protein) intermediates. A combination of tandem equilibrium isotope exchange (EIX) and a newly developed Tandem Modules Epimerase assay revealed the intrinsic epimerase activity of NanDH1 and NanDH5, from modules 1 and 5, respectively, of the nanchangmycin (1) PKS as well of NigDH1, from module 1 of the nigericin (3) PKS. Unexpectedly, all three epimerase-active DH domains were also found to possess intrinsic dehydratase activity, whereas the conventional DH domains, EryDH4, from module 4 of the erythromycin synthase, and NanDH2 from module 2 of the nanchangmycin synthase, were shown to have cryptic epimerase activity.

Mechanism and Stereochemistry of Polyketide Chain Elongation and Methyl Group Epimerization in Polyether Biosynthesis.

The polyketide synthases responsible for the biosynthesis of the polyether antibiotics nanchangmycin (1) and salinomycin (4) harbor a number of redox-inactive ketoreductase (KR0) domains that are implicated in the generation of C2-epimerized (2S)-2-methyl-3-ketoacyl-ACP intermediates. Evidence that the natural substrate for the polyether KR0 domains is, as predicted, a (2R)-2-methyl-3-ketoacyl-ACP intermediate, came from a newly developed coupled ketosynthase (KS)-ketoreductase (KR) assay that established that the decarboxylative condensation of methylmalonyl-CoA with S-propionyl-N-acetylcysteamine catalyzed by the Nan[KS1][AT1] didomain from module 1 of the nanchangmycin synthase generates exclusively the corresponding (2R)-2-methyl-3-ketopentanoyl-ACP (7a) product. In tandem equilibrium isotope exchange experiments, incubation of [2-2H]-(2R,3S)-2-methyl-3-hydroxypentanoyl-ACP (6a) with redox-active, epimerase-inactive EryKR6 from module 6 of the 6-deoxyerythronolide B synthase and catalytic quantities of NADP+ in the presence of redox-inactive, recombinant NanKR10 or NanKR50, from modules 1 and 5 of the nanchangmycin synthase, or recombinant SalKR70 from module 7 of the salinomycin synthase, resulted in first-order, time-dependent washout of deuterium from 6a. Control experiments confirmed that this washout was due to KR0-catalyzed isotope exchange of the reversibly generated, transiently formed oxidation product [2-2H]-(2R)-2-methyl-3-ketopentanoyl-ACP (7a), consistent with the proposed epimerase activity of each of the KR0 domains. Although they belong to the superfamily of short chain dehydrogenase-reductases, the epimerase-active KR0 domains from polyether synthases lack one or both residues of the conserved Tyr-Ser dyad that has previously been implicated in KR-catalyzed epimerizations.

Synthesis of a NbO Type Homochiral Cu(II) Metal-Organic Framework: Ferroelectric Behavior and Heterogeneous Catalysis of Three-Component Coupling and Pechmann Reactions.

A chiral tetracarboxylic acid ligand, H4L, incorporating the (S)-(+)-2-methylpiperazine moiety in its middle, solvothermally forms a homochiral Cu(II) framework, {[Cu2(L)(H2O)2]·(4DMF)(4H2O)}n (LCu). It forms a non-interpenetrated structure consisting of [Cu2(COO)4] paddle-wheel secondary bonding units (SBUs) with NbO topology. Interestingly, the framework LCu exhibits excellent ferroelectric properties. It shows a remnant polarization (Pr) of ∼3.5 µC cm-2 and a coercive field (Ec) of ∼12 kV cm-1 with a distinct electric hysteresis loop. Dielectric studies of LCu reveal almost frequency-independent behavior with a dielectric constant (εr) of ∼42 and a low dielectric loss (tan δ) of ∼0.04 up to 106 Hz, for potential use in high-frequency applications. In addition, activated framework LCu' having uncoordinated metal sites acts as an efficient heterogeneous catalyst in the three-component coupling of amines, aldehydes, and alkynes, as well as in Pechmann reactions of phenols with ß-ketoesters.

An efficient route to fabricate fatigue-free P(VDF-TrFE) capacitors with enhanced piezoelectric and ferroelectric properties and excellent thermal stability for sensing and memory applications.

P(VDF-TrFE), the best known ferroelectric polymer, suffers from a rather low piezoelectric response as well as poor electrical fatigue life, hampering its application potential. Herein, we report the fabrication of fatigue free poly(vinylidenedifluoride-trifluoroethylene) P(VDF-TrFE)-based capacitors with record piezoelectric coefficients and excellent thermal stability. We proposed a cost-effective and simple solution-based process to fabricate P(VDF-TrFE)-based memory capacitors with large polarization (8.9 µC cm-2), low voltage operation (15 V), and excellent fatigue endurance with 100% polarization retention up to 108 electrical switching cycles. The thin film capacitors fabricated using methyl ethyl ketone (MEK) and dimethyl sulfoxide (DMSO) as co-solvents also show a much higher piezoelectric coefficient (d33 = -60 pm V-1) than the previously reported capacitors and are also thermally stable up to 380 K, making them ideal candidates for ferro-, piezo-, and pyro-electric applications, even in devices operating above room temperature. The observed results are well supported by first principles calculations, FTIR, XPS, and evaluation of cohesion energy for crystallization by DSC.

Epimerase and Reductase Activities of Polyketide Synthase Ketoreductase Domains Utilize the Same Conserved Tyrosine and Serine Residues.

The role of the conserved active site tyrosine and serine residues in epimerization catalyzed by polyketide synthase ketoreductase (PKS KR) domains has been investigated. Both mutant and wild-type forms of epimerase-active KR domains, including the intrinsically redox-inactive EryKR3° and PicKR3° as well as redox-inactive mutants of EryKR1, were incubated with [2-(2)H]-(2R,3S)-2-methyl-3-hydroxypentanoyl-SACP ([2-(2)H]-2) and 0.05 equiv of NADP(+) in the presence of the redox-active, epimerase-inactive EryKR6 domain. The residual epimerase activity of each mutant was determined by tandem equilibrium isotope exchange, in which the first-order, time-dependent washout of isotope from 2 was monitored by liquid chromatography-tandem mass spectrometry with quantitation of the deuterium content of the diagnostic pantetheinate ejection fragment (4). Replacement of the active site Tyr or Ser residues, alone or together, significantly reduced the observed epimerase activity of each KR domain with minimal effect on substrate binding. Our results demonstrate that the epimerase and reductase activities of PKS KR domains share a common active site, with both reactions utilizing the same pair of Tyr and Ser residues.

The combined effect of mechanical strain and electric field cycling on the ferroelectric performance of P(VDF-TrFE) thin films on flexible substrates and underlying mechanisms.

In this manuscript, we study the combined effect of mechanical strain and electric field cycling on the ferroelectric properties and polarization fatigue of P(VDF-TrFE) based flexible thin film capacitors from the perspective of flexible memory applications. The devices show nearly 80% retention of ferroelectric polarization after 30 000 bending cycles at mechanical strains of up to ca. 0.8%, mimicking a typical number of bending cycles a product is expected to go through. On the other hand, electric field cycling of the unstrained as well as mechanically strained devices results in over 50% drop in the ferroelectric polarization of the capacitors within 105 bipolar switching cycles. We find that 20% reduction in the polarization upon mechanical cycling is due to the formation of cracks in P(VDF-TrFE) thin films whilst ca. 50% polarization reduction during purely electrical or mechano-electrical fatigue is concomitant with the development of bubbles in the top electrode of the devices which eventually coalesce to give rise to bursting and eventual delamination of the electrode. A detailed investigation into the electrical fatigue mechanisms shows that the fatigue is primarily driven by the degradation of the P(VDF-TrFE) thin films due to HF elimination triggered by a high enough electric field, also manifested by reduced crystallinity and a reduced number of total dipoles of P(VDF-TrFE) films. The results clearly suggest that polarization reduction upon electric field cycling i.e. electrical fatigue is a greater bottleneck in the use of flexible memory devices than the mechanical cycling.

Pediatric Resident Attitudes and Knowledge of Critical Congenital Heart Disease Screening.

This study aimed to understand the knowledge, attitudes and confidence level related to critical congenital heart disease (CCHD) screening among pediatric residents. Pediatric residents were assessed via an anonymous survey related to CCHD guidelines and procedures as set out by the New York State Department of Health. The survey was emailed to pediatric residents at a large academic institution. A teaching intervention was performed after the initial survey, which was followed by an identical after-intervention survey. Forty-two residents responded to the pre-intervention survey (n = 42), and forty post-intervention (n = 40). The mean composite knowledge score was 76 % pre-intervention and 92 % post-intervention, p < .001. Pre-intervention only 12 % of the respondents could answer all the questions correctly which increased to 60 % post-intervention. Confidence among residents regarding guidelines increased from 38 to 95 % post-intervention, p < .001. There was a positive correlation between the residents who felt confident of the guidelines and who answered correctly, r = .514, p < .001, n = 82. There was no significant difference between knowledge, attitudes or confidence level scores by year of training or the gender of the residents. Our study demonstrated a significant gap of knowledge among residents related to CCHD screening mandated by New York State health law. There was also a corresponding lack of confidence demonstrated by the residents in the guidelines. These data suggest that residents would benefit from further education on the proper implementation of a CCHD screening program. Further multicenter studies are warranted to assess similar gaps in other residency training programs in New York and wherever these screenings guidelines have been adopted.

Exploration of eosinopenia as a diagnostic parameter to differentiate sepsis from systemic inflammatory response syndrome: Results from an observational study.

AIM OF THE STUDY: Initial differentiation of sepsis from systemic inflammatory response syndrome (SIRS) is of prime importance for early institution of appropriate treatment. This study aimed to compare the differential diagnostic efficacy of absolute eosinophil count (AEC - a routinely available economic marker) with total leukocyte count (TLC) and procalcitonin (PCT - a costly marker available only in specialized settings). MATERIALS AND METHODS: In this prospective observational study, 170 patients of sepsis (severe sepsis = 125; SIRS = 45) were enrolled. AEC, TLC, and PCT were measured in the blood of all patients at the time of admission and data analyzed statistically. RESULTS: Median AEC was 0 cells/mm(3) in both SIRS and sepsis. TLC and PCT levels were significantly higher (P < 0.001) in culture negative, culture positive, and overall sepsis groups in comparison to SIRS group. At a cutoff of < 50 cells/mm(3), AEC demonstrated a sensitivity and specificity of 23% and 68%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of TLC were 57%, 71%, 85%, 37% and of PCT were 82.4%, 82.2%, 93%, and 63%, respectively with area under curve of 0.455 for AEC, 0.640 for TLC, 0.908 for PCT. CONCLUSIONS: This study suggests that eosinopenia is not a reliable diagnostic tool to differentiate sepsis from SIRS. PCT and TLC are better differential diagnostic biomarkers.

Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial.

BACKGROUND & AIMS: Little is known about whether probiotics can affect outcomes of patients with cirrhosis and hepatic encephalopathy (HE). We assessed the efficacy of a probiotic preparation in preventing the recurrence of HE (primary outcome) and reducing the number of hospitalizations and severity of liver disease in patients with cirrhosis. METHODS: We performed a double-blind trial at a tertiary care hospital in India. Patients with cirrhosis who had recovered from an episode of HE during the previous month were assigned randomly (using computer-generated allocation) to groups given a probiotic preparation (VSL#3, 9 × 10(11) bacteria; CD Pharma India Private Limited, New Delhi, India) (n = 66) or placebo (n = 64) daily for 6 months. RESULTS: There was a trend toward a reduction in the development of breakthrough HE among patients receiving the probiotic (34.8% in the probiotic group vs 51.6% in the placebo group; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.38-1.11; P = .12). Fewer patients in the probiotic group were hospitalized for HE (19.7% vs 42.2%, respectively; HR, 0.45; 95% CI, 0.23-0.87; P = .02) or for complications of cirrhosis (24.2%) than in the placebo group (45.3%) (HR, 0.52; 95% CI, 0.28-0.95; P = .034). Child-Turcotte-Pugh and model for end-stage liver disease scores improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group. There were no adverse events related to VSL#3. CONCLUSIONS: Over a 6-month period, daily intake of VSL#3 significantly reduced the risk of hospitalization for HE, as well as Child-Turcotte-Pugh and model for end-stage liver disease scores, in patients with cirrhosis. ClinicalTrials.gov number: NCT01110447.