Determinants of outcomes and advances in CD19-directed chimeric antigen receptor therapy for B-cell acute lymphoblastic leukemia.

Relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive B-cell neoplasm associated with poor outcomes. Conventional multiagent chemotherapy and bispecific antibody therapy may induce remission; however, relapse rates remain high and overall survival is poor. Chimeric antigen receptor T-cell (CAR-T) therapy provides durable, deep complete remission, and long-term cures in relapsed and refractory B-ALL. However, with this new treatment modality, 10%-30% of patients do not achieve remission, and over 50% experience relapse after therapy. Currently, there are two approved CD19-specific CAR-T cell constructs in B-ALL, Tisagenlecleucel and Brexucabtagene Autoleucel by the United States Food and Drug Administration, and the European Medicines Agency (EMA). In this review, we discuss patients, disease, and CAR-T predictors of outcomes in B-ALL. We describe the two approved CD19-directed CAR-T cell products, review the current literature, and discuss factors associated with high risks of therapy failure and future direction in CAR-T cell therapy for B-ALL.

Confinement-induced self-assembly of a diblock copolymer within a non-uniform cylindrical nanopore.

The self-assembly of a diblock copolymer melt confined within a non-uniform cylindrical nanopore is studied using the self-consistent field theory. The non-uniformity manifests in the form of a converging-diverging cylindrical nanopore. The axial variation in pore diameter presents a range of curvatures within the same confinement pore as opposed to a single curvature in a uniform-diameter cylindrical pore. The introduction of multiple curvatures leads to the formation of novel microstructures not accessible in uniform cylindrical confinement. The well-known equilibrium structures like a single helix, double helices, and concentric lamella under cylindrical confinement transition into new morphologies such as hyperboloidal phases, microstructures containing rings with a bead, rings with spheres, and a squeezed helical phase as the pore diameter varies axially. The converging-diverging geometry of the confining pore renders the helical phases seen in the cylindrical pore less favorable. A phase diagram in the parametric space of the block fraction and the ratio of the smallest and largest pore radii has been constructed to depict the order-order transition of various microstructures. The ratio of radii, a measure of the non-uniformity of the pore, along with the pore length brings out some interesting morphologies. The mechanism of these structural transitions is understood as the interplay between the variation in pore curvature attributed to the non-uniformity, the spontaneous curvature of the block copolymer interface, and the enthalpic interaction between the segregated blocks.

Fungal pectinases: an insight into production, innovations and applications.

The fungal system holds morphological plasticity and metabolic versatility which makes it unique. Fungal habitat ranges from the Arctic region to the fertile mainland, including tropical rainforests, and temperate deserts. They possess a wide range of lifestyles behaving as saprophytic, parasitic, opportunistic, and obligate symbionts. These eukaryotic microbes can survive any living condition and adapt to behave as extremophiles, mesophiles, thermophiles, or even psychrophile organisms. This behaviour has been exploited to yield microbial enzymes which can survive in extreme environments. The cost-effective production, stable catalytic behaviour and ease of genetic manipulation make them prominent sources of several industrially important enzymes. Pectinases are a class of pectin-degrading enzymes that show different mechanisms and substrate specificities to release end products. The pectinase family of enzymes is produced by microbial sources such as bacteria, fungi, actinomycetes, plants, and animals. Fungal pectinases having high specificity for natural sources and higher stabilities and catalytic activities make them promising green catalysts for industrial applications. Pectinases from different microbial sources have been investigated for their industrial applications. However, their relevance in the food and textile industries is remarkable and has been extensively studied. The focus of this review is to provide comprehensive information on the current findings on fungal pectinases targeting diverse sources of fungal strains, their production by fermentation techniques, and a summary of purification strategies. Studies on pectinases regarding innovations comprising bioreactor-based production, immobilization of pectinases, in silico and expression studies, directed evolution, and omics-driven approaches specifically by fungal microbiota have been summarized.

Self-organization of a 4-miktoarm star block copolymer induced by cylindrical confinement.

Self-consistent field calculations have been carried out to reveal the self-assembly behavior of a melt of the ABCD star tetrablock copolymer confined within a cylindrical nanopore. The miktoarm star block copolymer exhibits a rich self-assembly behavior with a myriad of interesting three-dimensional ordered phases with the potential to produce advanced nanomaterials. The broad array of ordered mesophases includes helical microstructures, stack of rings/doughnuts, honeycomb structure, and perforated lamella with beads, depending on the individual block fractions and the size of the cylindrical nanopore. Such chiral motifs generated from achiral polymeric molecules are fascinating due to their superior performance in sophisticated opto-electronic devices. The study also demonstrates an interesting morphology, viz. a honeycomb structure, obtained from the self-organization of ABCD star block copolymer molecules with equal block fractions. The system exhibits order-order phase transition covering a range of ordered morphologies by changing either the block fraction or the nanopore radius. A representative phase diagram in terms of block fractions is constructed. These novel ordered microstructures, arising mainly out of structural frustration and confinement-induced entropy loss, can serve as structural scaffolds to host the spatial distribution of nanoparticles resulting into novel nanocomposites with significantly enhanced as well as controllable properties.

Developability assessment for monoclonal antibody drug candidates: a case study.

Various screening approaches are used by industry to evaluate development risks associated with discovery candidates. This process has become more complicated with biological therapeutics, a class dominated by monoclonal antibodies (mAb), and, increasingly, their derivative constructs. Effective early assessment for drug-like properties (DLP) can save time and costs by allowing a more complete consideration of issues that could impact the desired end result of a stable drug product. Here we report a case study of four IgG1 mAbs, with sequence variations in the variable domain region, screened as a set of possible drug candidates. Our comprehensive, tiered approach used a battery of analytical tools to assess molecular characteristics, conformational stability, colloidal stability, and short-term storage stability. While most DLP for the four candidates were developmentally acceptable and comparable, mAb-2 was associated with adverse colloidal properties. Further investigation of mAb-2 in an expanded pH range revealed a propensity for phase separation, indicating a need for the additional product development effort. Our results support that comprehensive DLP assessments in an expanded pH range are beneficial in identifying development options for promising molecules that show challenging stability trends. This adaptable approach may be especially useful in the development of increasingly complex antibody constructs.

Diblock copolymer templated self-assembly of grafted nanoparticles under circular pore confinement.

Geometrical confinement plays an important role in generating novel molecular organization arising out of structural frustration and confinement-induced entropy loss. In the present study, we perform self-consistent mean-field theoretical calculations to examine a mixture of a diblock copolymer and polymer grafted nanoparticles confined in a cylindrical nanopore. The two-dimensional analysis is aimed at constructing the equilibrium nanostructures decorated with particles in an ordered manner. The rich variety of ordered mesophases of the diblock copolymer under confinement provide a template to achieve the self-assembly of nanoparticles in a selective domain. The localization behavior of nanoparticles under confinement is found to be qualitatively different from that in a bulk system. In particular, for the concentric lamellar phase the particles tend to localize predominantly in the region of greater curvature within the curved lamella. The incorporation of grafted nanoparticles also results in a transition in ordered phases. Various equilibrium morphologies are observed depending upon the degree of confinement, particle loading, density of grafted segments and selectivity of the particle core to the polymeric species. The ordering of particles and the ensuing equilibrium nanostructures are analyzed. The comprehensive understanding of the self-assembly behavior of particles enables one to design novel nanomaterials with desirable material properties.

Radiology, Mobile Devices, and Internet of Things (IoT).

Radiology by its nature is intricately connected to the Internet and is at the forefront of technology in medicine. The past few years have seen a dramatic rise in Internet-based technology in healthcare, with imaging as a core application. Numerous Internet-based applications and technologies have made forays into medicine, and for radiology it is more seamless than in other clinical specialties. Many applications in the practice of radiology are Internet based and more applications are being added every day. Introduction of mobile devices and their integration into imaging workflow has reinforced the role played by the Internet in radiology. Due to the rapid proliferation of wearable devices and smartphones, IoT-enabled technology is evolving healthcare from conventional hub-based systems to more personalized healthcare systems. This article briefly discusses how the IoT plays a useful role in daily imaging workflow and current and potential future applications, how mobile devices can be integrated into radiology workflows, and the impact of the IoT on resident and medical student education, research, and patient engagement in radiology.

Self-assembly of grafted nanoparticles in the lamellar mesophase of a symmetric triblock copolymer.

The self-assembly behavior of brush-grafted nanoparticles in the ordered mesophase of a symmetric triblock copolymer is studied using the self-consistent field theory. The emphasis is on the templated localization of nanoparticles in a two-dimensional lamellar microstructure formed by an ABA triblock copolymer. While particles grafted with either A-type or B-type polymeric chains preferentially localize in the respective micro-domain, the spatial distribution of particles within the selective domain is of great interest in controlling the properties of the nano-ordered morphologies. As the mid-block of an ABA triblock copolymer is entropically constrained, the localization behavior of B-grafted nanoparticles is found to be qualitatively different from that of A-grafted particles. The absence of free ends and the bridge conformation of the mid-block tend to reduce the spatial segregation of B-grafted particles at the center of the B-domain, a behavior in contrast to an AB diblock copolymer. Under similar conditions, while A-grafted particles self-assemble at the center of the A-domain, the B-grafted particles with a non-selective core segregate predominantly at the interface of A and B domains, especially when the particle size is large or grafting is weak. Upon increasing the grafting density, the morphology transitions from interface to center localization. The spatial localization of particles, governed by the interplay of enthalpic and entropic contributions to the free energy, is found to be strongly influenced by particle size, selectivity, volume fraction, and number and size of grafted chains. Controlling the self-assembly behavior of particles by tuning these parameters will be immensely helpful in designing advanced nanostructured materials with desired physical properties.

Assessing the Effect of Weight-Based Protocol Modifications to Lower Dose for CT-Guided Hepatic and Renal Tumor Radiofrequency Ablations.

OBJECTIVE: This study assessed radiation dose after CT-guided percutaneous radiofrequency ablations (RFAs) of hepatic and renal tumors and the effect of weight-based CT protocol modification for lowering overall dose in these procedures. MATERIALS AND METHODS: CT-guided RFA for renal and hepatic ablations performed from January 1, 2009, through December 31, 2009, were retrospectively reviewed (90 men and 48 women; age, 42-81 years). The radiation dose was recorded during each of the following steps: planning, performing, and postprocedure. Weight-based protocol modification changes in tube voltage and tube current were then applied to renal and hepatic ablations performed subsequently (18 men and 11 women; age, 48-82 years). Image quality, needle localization, lesion detection, ability to detect complications, and overall operator satisfaction were noted for each case (score, 1-5). Dose reduction after modification was then calculated. RESULTS: Retrospective analysis found a mean (± SD) overall CT dose index (CTDI) for CT-guided RFA to be 16.5 ± 2.3 mGy. After protocol modification, the mean CTDI decreased to 6.63 ± 0.67 mGy, a 59.6% reduction overall; for hepatic ablations, the reduction was 65.96% (p < 0.0001) and the reduction for renal ablations was 38.97% (p = 0.0153). Image quality analysis showed high operator satisfaction (3-5), including adequate needle localization (4-5), lesion visibility (3-5), and high performer confidence (4-5). Higher dose reduction was noted for patients weighing more than 180 lb (82 kg) (p < 0.0001). CONCLUSION: Simple weight-based CT protocol modifications can significantly reduce radiation dose during CT-guided percutaneous ablations in the liver and kidneys without significantly sacrificing image quality.

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.

Management of drug eluting stent in-stent restenosis: A systematic review and meta-analysis.

BACKGROUND: The optimal management for coronary drug eluting stent in-stent restenosis (DES ISR) is unclear. We performed a meta-analysis of observational and randomized studies to compare the outcomes of management of DES ISR using DES, drug eluting balloon (DEB), or balloon angioplasty (BA). METHODS: Eligible studies (25 single arm and 13 comparative, including 4 randomized studies with a total of 7,474 patients with DES ISR) were identified using MEDLINE search and proceedings of international meetings. Outcomes studied include major adverse cardiac events (MACE), target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis (ST), and mortality. Follow-up ranged from 0.5 to 3.5 years (mean 1.4 years). RESULTS: The rate of TLR was significantly lower in the DES (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.36-0.69) and DEB (OR 0.31, 95% CI 0.18-0.55) groups compared to BA. Similarly, TVR rate was significantly lower in the DES (OR 0.55, 95% CI 0.39-0.77) and DEB (OR 0.32, 95% CI 0.18-0.58) groups compared to BA. All other outcomes were similar between the DES/BA and DEB/BA comparisons. TLR was significantly lower in the DES group compared to BA for vessels < or > 2.75 mm. CONCLUSION: Treatment of coronary DES ISR with DES or DEB is associated with a reduction in the risk of TLR and TVR compared to BA alone. The relative risk reduction for TLR with DES is similar to DEB. DEBs have a potential role in the treatment of DES ISR by avoiding placement of another layer of stent. © 2015 Wiley Periodicals, Inc.

Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer-related mortality in the United States. Because of the lack of viable treatment options for HCC, prevention in high-risk patients has been proposed as an alternative strategy. The main risk factor for HCC is cirrhosis and several lines of evidence implicate epidermal growth factor (EGF) in the progression of cirrhosis and development of HCC. We therefore examined the effects of the EGF receptor (EGFR) inhibitor erlotinib on liver fibrogenesis and hepatocellular transformation in three different animal models of progressive cirrhosis: a rat model induced by repeated, low-dose injections of diethylnitrosamine (DEN), a mouse model induced by carbon tetrachloride (CCl4 ), and a rat model induced by bile duct ligation (BDL). Erlotinib reduced EGFR phosphorylation in hepatic stellate cells (HSC) and reduced the total number of activated HSC. Erlotinib also decreased hepatocyte proliferation and liver injury. Consistent with all these findings, pharmacological inhibition of EGFR signaling effectively prevented the progression of cirrhosis and regressed fibrosis in some animals. Moreover, by alleviating the underlying liver disease, erlotinib blocked the development of HCC and its therapeutic efficacy could be monitored with a previously reported gene expression signature predictive of HCC risk in human cirrhosis patients. CONCLUSION: These data suggest that EGFR inhibition using Food and Drug Administration-approved inhibitors provides a promising therapeutic approach for reduction of fibrogenesis and prevention of HCC in high-risk cirrhosis patients who can be identified and monitored by gene expression signatures.

Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells.

Under the instruction of cell-fate-determining, DNA-binding transcription factors, chromatin-modifying enzymes mediate and maintain cell states throughout development in multicellular organisms. Currently, small molecules modulating the activity of several classes of chromatin-modifying enzymes are available, including clinically approved histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors. We describe the genome-wide expression changes induced by 29 compounds targeting HDACs, DNMTs, histone lysine methyltransferases (HKMTs), and protein arginine methyltransferases (PRMTs) in pancreatic α- and ß-cell lines. HDAC inhibitors regulate several hundred transcripts irrespective of the cell type, with distinct clusters of dissimilar activity for hydroxamic acids and orthoamino anilides. In contrast, compounds targeting histone methyltransferases modulate the expression of restricted gene sets in distinct cell types. For example, we find that G9a/GLP methyltransferase inhibitors selectively up-regulate the cholesterol biosynthetic pathway in pancreatic but not liver cells. These data suggest that, despite their conservation across the entire genome and in different cell types, chromatin pathways can be targeted to modulate the expression of selected transcripts.

Renin-angiotensin system blockade therapy after surgical aortic valve replacement for severe aortic stenosis: a cohort study.

BACKGROUND: Data are lacking on the effect of renin-angiotensin system (RAS) blockade therapy with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers after surgical aortic valve replacement (SAVR) for severe aortic stenosis (AS). OBJECTIVE: To investigate the association between RAS blockade therapy and outcomes after SAVR for severe AS. DESIGN: Retrospective study. SETTING: Single tertiary referral care center. PATIENTS: Patients who were prescribed angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers after SAVR for severe AS between 1991 and 2010 who had at least 2 refills 90 days apart and at least a 6-month follow-up constituted the RAS blockade group (n = 741). Patients who did not receive these prescriptions were in the untreated group (n = 1011). Unadjusted and propensity-matched analyses (594 matched pairs of treated and untreated patients) were performed. MEASUREMENTS: The primary outcome was survival rates after SAVR. Secondary end points were changes in left ventricular mass index, left ventricular ejection fraction, and left atrial size. RESULTS: Overall unadjusted estimated survival rates at 1, 5, and 10 years were significantly greater in the RAS blockade group than in the non-RAS blockade group (99%, 90%, and 60% vs. 99%, 81%, and 53%, respectively; P < 0.001). Among propensity-matched patients, estimated survival rates at 1, 5, and 10 years remained significantly greater in the RAS blockade group than in the non-RAS blockade group (99%, 90%, and 71% vs. 96%, 78%, and 49%, respectively; P < 0.001). For the matched cohorts, the groups did not significantly differ in the change in left ventricular mass index (P = 0.37), left ventricular ejection fraction (P = 0.67), or left atrial size (P = 0.43) after SAVR on echocardiographic analysis. LIMITATION: Retrospective, single-center analysis. CONCLUSION: Renin-angiotensin system blockade therapy is associated with increased survival rates in patients after SAVR for severe AS. A randomized trial of RAS blockade therapy after SAVR should be considered. PRIMARY FUNDING SOURCE: None.

Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis.

BACKGROUND & AIMS: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.

Identification of genes involved in carbon metabolism from Eleusine coracana (L.) for understanding their light-mediated entrainment and regulation.

KEY MESSAGE: The study would be helpful in understanding the synchronization of genes of a pathway and its effect on carbon metabolism which can be further utilized for better agronomic performance. Finger millet (Eleusine coracana) is a C4 crop with high nitrogen use efficiency (NUE) said to be organic by default. Being carbon and nitrogen mutually exclusive, in the present study, it was investigated how light regulates the expression of genes of carbon metabolism and photosynthesis in two finger millet genotypes (GE 3885 and GE 1437) with differing grain protein content (13.8 and 6.2%). Different genes associated with carbon metabolism were isolated (Cab, RBCS, PEPC, PPDK, PEPC-k, ME, SPS, PK, 14-3-3 and SnRK1) and the co-expression of Dof1 and these genes was investigated under different light-dark conditions. The deduced protein sequences of isolated genes showed relationship of marked variations with their homolog which might corresponds to difference in photosynthetic efficiency between finger millet and other plants. In 24 h day-night conditions, the identified genes exhibited diurnal rhythm in both genotypes with different time of peak expression. In dark, the expression of identified genes in both genotypes oscillated with varied amplitude indicating their control by an endogenous clock. However, Cab, RBCS and PPDK showed no oscillations suggesting that genes are light inducible. Exceptionally, ME transcript showed differential response within genotypes. Upon illumination, genes were induced within the measured period indicating that light is a signal involved in the entrainment of these genes. Exception was ME and SnRK1 in GE 1437. We conclude that expression of Dof1 in higher grain protein genotype was more consistent with the expression of carbon metabolism genes under study suggesting that Dof1 differentially regulates the expression of these light inducible genes and simultaneously controls the grain protein content in finger millet genotypes.

Recycling of printed Xerographic paper using Aspergillus assiutensis enzyme cocktail: an integrated approach to sustainable development.

To overcome the human and animal survivability risk, sustainable development is the only option on earth that can be achieved through the maximum use of renewable environmental resources. Recycling of waste paper is an emerging waste management approach to conserve natural resources. Herein, we studied enzyme-mediated process to recycle the xerographic paper by using the crude fungal extract from indigenously isolated fungi identified as Aspergillus assiutensis. The fungal enzyme cocktail has been characterized for the production of multiple enzymes namely cellulase, amylase, xylanase, pectinase, and protease. All these enzymes have pH optima in the acidic range and except cellulase and all the enzymes are stable from 10 to 80 C. In the zymogram analysis, pectinase, xylanase, amylase, and cellulase were detected at 68 kDa, ~ 54 kDa, 38 kDa, and 30 kDa, respectively. Also, the presence of protease was confirmed by the clear zone at 68, 31, and 16 kDa. A 26% decrease in the kappa number and reduction in Hex A of the pulp was observed on the treatment of the pulp with enzyme as compared to the control pulp without any treatment. The physical and chemical properties of the pulp were also improved by enzyme-mediated pulping as compared to the control The physiochemical parameter of the effluent like TDS was reduced (397 ppm) significantly in comparison to chemical deinking process and it was within the permissible limit. BOD and alkalinity were reduced when the enzymes and chemical dosage were used in combination. These results indicate that chemi-enzymatic deinking is most promising to reduce or remove the pollution parameters including ink and this approach can be used in the paper and pulp industry for sustainable development.

Nasal Pyriform Aperture Stenosis in a Newborn: When to Operate.

Congenital nasal pyriform aperture stenosis (CNPAS) is a very rare cause of neonatal respiratory distress and is often missed because of its rarity. It arises from the overgrowth of the nasal process of the maxilla. Maxillofacial CT scan findings of pyriform aperture width <11 mm in a full-term baby, median central incisor, triangular-shaped palate, and median palatal ridge confirm the diagnosis. We describe here a case of CNPAS admitted with respiratory distress that increased further on feeding. An infant feeding tube of size 6 was not negotiable through the nostrils. Resistance was appreciated at the inlet of the nostril. Maxillofacial CT showed pyriform aperture stenosis of 3.4 mm, suggesting CNPAS. The child could not be weaned off a high-flow nasal cannula despite conservative management with decongestants, steroids spray, dilatation, and stenting for 20 days. Subsequently, surgical widening of the nasal aperture by a sublabial approach was done. The child was discharged on the 10th postoperative day on full oral feeds. It is important to suspect CNPAS in neonates with respiratory distress where other common causes have been ruled out, as it can be treated by surgery in cases refractory to conservative management.

Comparative evaluation of resin-based sealers and bioceramic sealers for postoperative pain after endodontic treatment: A systematic review.

The systematic review aimed to compare and evaluate the effect of resin-based sealers and bioceramic sealers on postoperative pain after endodontic treatment. Two reviewers independently conducted electronic search in PubMed, the Web of Science, ScienceDirect, the Wiley Online Library, SpringerLink, Google Scholar, and the Cochrane Library, employing a complete dual-review process to ensure the inclusion of all relevant studies in the review. The search was carried out until November 2021. After selecting eligible studies, the risk of bias assessment was carried out using the revised Cochrane risk-ofbias tool for randomized trials (RoB 2). A total of 1,931 studies were identified from the electronic search, and finally 10 studies were included after full-text assessment. In all our included studies, the visual analog scale (VAS) was used for recording pain scores. Most of the studies recorded pain intensity starting from 6 h to 7 days. The results showed that there was no significant difference between resin-based sealers and bioceramic sealers in terms of incidence or intensity of postoperative pain at any point in time.