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Background: The role of epicardial adipose tissue (EAT) in heart failure with preserved ejection fraction (HFpEF) remains to be defined. Methods: A consecutive series of outpatients with chronic heart failure-heart failure with reduced ejection fraction (HFrEF) and HFpEF and/or diastolic dysfunction-had EAT assessed by echocardiographic measurement and related to indices of cardiac structure and function. Results: Epicardial fat thickness was significantly ( p < 0.05) greater in HFpEF ( N = 141) with a mean of 6.7 ± 1.6 mm compared with a mean of 5.1 ± 1.0 mm in HFrEF ( n = 40). After adjusting for the relationship with BMI, in HFpEF, epicardial fat was significantly ( p < 0.05) negatively correlated with left ventricular internal diameter end diastole (LVIDd), left ventricular internal diameter end systole (LVIDs), left ventricular (LV) end-diastolic volume (EDV) index, lateral e', septal e', right atrial (RA) volume index, and hemoglobin (Hgb). The association with Hgb was no longer significant after adjusting for the effect of age. HFpEF was associated with smaller LVIDd, LVIDs, LV EDV indexes, and left atrial (LA) and RA volume indexes. Conclusions: Epicardial fat is significantly ( p < 0.05) greater in HFpEF than HFrEF. Epicardial fat is associated with smaller cardiac chamber sizes in HFpEF suggesting that epicardial fat acts as a constraint to cardiac dilation.

Posterolateral impingement is sometimes diagnosed as a cause of refractory elbow pain, often after other treatments have been tried for common conditions such as lateral epicondylitis (tennis elbow) or subtly different conditions common in throwing athletes, such as valgus extension overload syndrome. Arthroscopic surgical treatment is effective when targeting abnormal anatomy such as plical folds. Partial excision of the olecranon must be undertaken with caution because it can lead to instability. This systematic review of the current literature uses a narrative synthesis to identify anatomical morphological variations of the olecranon, humeral and capitellar geometry, and overloading of the lateral part of the elbow as causative factors for this condition and discusses how arthroscopic techniques can resolve symptoms. Further understanding of the static and dynamic anatomy of the lateral part of the elbow will help to develop future treatment and preventive strategies.

Brassica crops are susceptible to diseases which can be mitigated by breeding for resistance. MAMPs (microbe-associated molecular patterns) are conserved molecules of pathogens that elicit host defences known as pattern-triggered immunity (PTI). Necrosis and Ethylene-inducing peptide 1-like proteins (NLPs) are MAMPs found in a wide range of phytopathogens. We studied the response to BcNEP2, a representative NLP from Botrytis cinerea, and showed that it contributes to disease resistance in Brassica napus. To map regions conferring NLP response, we used the production of reactive oxygen species (ROS) induced during PTI across a population of diverse B. napus accessions for associative transcriptomics (AT), and bulk segregant analysis (BSA) on DNA pools created from a cross of NLP-responsive and non-responsive lines. In silico mapping with AT identified two peaks for NLP responsiveness on chromosomes A04 and C05 whereas the BSA identified one peak on A04. BSA delimited the region for NLP-responsiveness to 3 Mbp, containing ~245 genes on the Darmor-bzh reference genome and four co-segregating KASP markers were identified. The same pipeline with the ZS11 genome confirmed the highest-associated region on chromosome A04. Comparative BLAST analysis revealed unannotated clusters of receptor-like protein (RLP) homologues on ZS11 chromosome A04. However, no specific RLP homologue conferring NLP response could be identified. Our results also suggest that BR-SIGNALLING KINASE1 may be involved with modulating the NLP response. Overall, we demonstrate that responsiveness to NLP contributes to disease resistance in B. napus and define the associated genomic location. These results can have practical application in crop improvement., (© 2024 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Introduction: The United States Centers for Disease Control and Prevention (CDC) advises testing individuals for COVID-19 after exposure or if they display symptoms. However, a deeper understanding of demographic factors associated with testing hesitancy is necessary., Methods: A US nationwide cross-sectional survey of adults with risk factors for developing severe COVID-19 ("high-risk" individuals) was conducted from August 18-September 5, 2023. Objectives included characterizing demographics and attitudes associated with COVID-19 testing. Inverse propensity weighting was used to weight the data to accurately reflect the high-risk adult US population as reflected in IQVIA medical claims data. We describe here the weighted results modeled to characterize demographic factors driving hesitancy., Results: In the weighted sample of 5019 respondents at high risk for severe COVID-19, 58.2% were female, 37.8% were ≥ 65 years old, 77.1% were White, and 13.9% had a postgraduate degree. Overall, 67% were Non-testers (who indicated that they were unlikely or unsure of their likelihood of being tested within the next 6 months); these respondents were significantly more likely than Testers (who indicated a higher probability of testing within 6 months) to be female (60.2 vs. 54.1%; odds ratio [OR] [95% confidence interval (CI)], 1.3 [1.1‒1.4]), aged ≥ 65 years old (41.5 vs. 30.3%; OR [95% CI] compared with ages 18‒34 years, 0.6 [0.5‒0.7]), White (82.1 vs. 66.8%; OR [95% CI], 1.4 [1.1‒1.8]), and to identify as politically conservative (40.9 vs. 18.1%; OR [95% CI], 2.6 [2.3‒2.9]). In contrast, Testers were significantly more likely than Non-testers to have previous experience with COVID-19 testing, infection, or vaccination; greater knowledge regarding COVID-19 and testing; greater healthcare engagement; and concerns about COVID-19., Conclusions: Older, female, White, rural-dwelling, and politically conservative high-risk adults are the most likely individuals to experience COVID-19 testing hesitancy. Understanding these demographic factors will help guide strategies to improve US testing rates., (© 2024. The Author(s).)

Key Message: Using associative transcriptomics, our study identifies genes conferring resistance to four diverse fungal pathogens in crops, emphasizing key genetic determinants of multi-pathogen resistance. Crops are affected by several pathogens, but these are rarely studied in parallel to identify common and unique genetic factors controlling diseases. Broad-spectrum quantitative disease resistance (QDR) is desirable for crop breeding as it confers resistance to several pathogen species. Here, we use associative transcriptomics (AT) to identify candidate gene loci associated with Brassica napus constitutive QDR to four contrasting fungal pathogens: Alternaria brassicicola, Botrytis cinerea, Pyrenopeziza brassicae, and Verticillium longisporum. We did not identify any shared loci associated with broad-spectrum QDR to fungal pathogens with contrasting lifestyles. Instead, we observed QDR dependent on the lifestyle of the pathogen-hemibiotrophic and necrotrophic pathogens had distinct QDR responses and associated loci, including some loci associated with early immunity. Furthermore, we identify a genomic deletion associated with resistance to V. longisporum and potentially broad-spectrum QDR. This is the first time AT has been used for several pathosystems simultaneously to identify host genetic loci involved in broad-spectrum QDR. We highlight constitutive expressed candidate loci for broad-spectrum QDR with no antagonistic effects on susceptibility to the other pathogens studies as candidates for crop breeding. In conclusion, this study represents an advancement in our understanding of broad-spectrum QDR in B. napus and is a significant resource for the scientific community., (© 2024. The Author(s).)

Background: Flowering plays an important role in completing the reproductive cycle of plants and obtaining next generation of plants. In case of citrus, it may take more than a year to achieve progeny. Therefore, in order to fasten the breeding processes, the juvenility period needs to be reduced. The juvenility in plants is regulated by set of various flowering genes. The citrus fruit and leaves possess various medicinal properties and are subjected to intensive breeding programs to produce hybrids with improved quality traits. In order to break juvenility in Citrus, it is important to study the role of flowering genes. The present study involved identification of genes regulating flowering in Citrus sinensis L. Osbeck via homology based approach. The structural and functional characterization of these genes would help in targeting genome editing techniques to induce mutations in these genes for producing desirable results., Results: A total of 43 genes were identified which were located on all the 9 chromosomes of citrus. The in-silico analysis was performed to determine the genetic structure, conserved motifs, cis-regulatory elements (CREs) and phylogenetic relationship of the genes. A total of 10 CREs responsible for flowering were detected in 33 genes and 8 conserved motifs were identified in all the genes. The protein structure, protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to study the functioning of these genes which revealed the involvement of flowering proteins in circadian rhythm pathways. The gene ontology (GO) and gene function analysis was performed to functionally annotate the genes. The structure of the genes and proteins were also compared among other Citrus species to study the evolutionary relationship among them. The expression study revealed the expression of flowering genes in floral buds and ovaries. The qRT-PCR analysis revealed that the flowering genes were highly expressed in bud stage, fully grown flower and early stage of fruit development., Conclusions: The findings suggested that the flowering genes were highly conserved in citrus species. The qRT-PCR analysis revealed the tissue specific expression of flowering genes (CsFT, CsCO, CsSOC, CsAP, CsSEP and CsLFY) which would help in easy detection and targeting of genes through various forward and reverse genetic approaches., (© 2024. The Author(s).)

Intrahepatic macrophages in nonalcoholic steatohepatitis (NASH) are heterogenous and include proinflammatory recruited monocyte-derived macrophages. The receptor for advanced glycation endproducts (RAGE) is expressed on macrophages and can be activated by damage associated molecular patterns (DAMPs) upregulated in NASH, yet the role of macrophage-specific RAGE signaling in NASH is unclear. Therefore, we hypothesized that RAGE-expressing macrophages are proinflammatory and mediate liver inflammation in NASH. Compared with healthy controls, RAGE expression was increased in liver biopsies from patients with NASH. In a high-fat, -fructose, and -cholesterol-induced (FFC)-induced murine model of NASH, RAGE expression was increased, specifically on recruited macrophages. FFC mice that received a pharmacological inhibitor of RAGE (TTP488), and myeloid-specific RAGE KO mice (RAGE-MKO) had attenuated liver injury associated with a reduced accumulation of RAGE+ recruited macrophages. Transcriptomics analysis suggested that pathways of macrophage and T cell activation were upregulated by FFC diet, inhibited by TTP488 treatment, and reduced in RAGE-MKO mice. Correspondingly, the secretome of ligand-stimulated BM-derived macrophages from RAGE-MKO mice had an attenuated capacity to activate CD8+ T cells. Our data implicate RAGE as what we propose to be a novel and potentially targetable mediator of the proinflammatory signaling of recruited macrophages in NASH.

Asthma is a debilitating chronic disease that renders individuals physically as well as mentally sick. The perception of stigmatization further leads to inappropriate control of asthma resulting in a bidirectional relationship. A prospective, cross-sectional study was conducted in a tertiary care centre of semi urban area of north India during 2021-2022. Three hundred cases of bronchial asthma and 50 healthy controls were enrolled. The asthma control test (ACT) was used to evaluate the control of asthma. Stigma and self-esteem were measured with the use of 28 item self-stigma scale, Rosenberg self-esteem scale, and stigma-related social problem scale (SPSS). The impact of sociodemographic and clinical profiles on stigma and self-esteem was evaluated. Correlation of different scales with each other was done along with. The mean age of asthmatic patients was 47.41±15.507 years with 56% being females; 49.3% of patients were well controlled and 36.3% were partly controlled. Positive subscales of 28 item self-stigma scale, Rosenberg self-esteem scale and SSPS showed statistically significant differences between cases and controls (p<0.001). ACT significantly correlated with 28 item self-stigma scale, Rosenberg self-esteem scale and SSPS, and all three stigma and self-esteem scales correlated significantly with each other.

Background: Adverse drug reactions (ADRs) have national and international monitoring and are part of teaching-learning of undergraduate medical course and curriculum., Objectives: To find the knowledge and perception of ADRs among undergraduate medical students in a tertiary care teaching institute in eastern India., Materials and Methods: This was an observational cross-sectional study conducted among the MBBS medical students by administration of pre-designed, pre-tested, semi-structured questionnaires. The data on their knowledge and candid reflections on ADRs were analyzed question by question using software and compared with peers., Results: The responses from the participants on knowledge and perception of ADRs varied widely. Final-year students had the most precise response on classification, filing an ADR report, national reporting centers, and the first step in monitoring ADRs; the majority accepted their first- hand experience and legal and professional responsibilities on ADRs. Third-year students responded well on objectives, methods, and scope of patients on direct reporting or drug overdose and monitoring; respect patient confidentiality while reporting; and expect feedback from monitoring centers, with special training on ADR. Second-year students responded well on definitions, pharmacovigilance programs in India, alertness of banned drugs because of ADR, and related capacity building., Conclusions: The awareness and insight on ADRs of the undergraduate medical students were quite reasonable. However, further reinforcement is needed in future to be updated to relevant issues to their practice as primary care physicians., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Purpose: Carboxymethylcellulose is an artificial tear ingredient known to decrease gut microbiome diversity when ingested. This study examines the effect of carboxymethylcellulose on ocular surface microbiome diversity and composition., Methods: Healthy adult participants without significant ophthalmic disease or concurrent carboxymethylcellulose artificial tear use were allocated randomly to take carboxymethylcellulose or control polyethylene glycol artificial tears for seven days. Conjunctival swabs were collected before and after artificial tear treatment. This trial is registered at clinicaltrials.gov (NCT05292755). Primary outcomes included abundance of bacterial taxa and microbiome diversity as measured by the Chao-1 richness estimate, Shannon's phylogenetic diversity index, and UniFrac analysis. Secondary outcomes included Ocular Surface Disease Index scores and artificial tear compliance., Results: Of the 80 enrolled participants, 66 completed the trial. Neither intervention affected Chao-1 richness (analysis of variance [ANOVA], P = 0.231) or Shannon's diversity index (ANOVA, P = 0.224). Microbiome samples did not separate by time point (permutation multivariate analysis of variance [PERMANOVA], P = 0.223) or intervention group (PERMANOVA, P = 0.668). LEfSe taxonomic analysis revealed that carboxymethylcellulose depleted several taxa including Bacteroides and Lachnoclostridium, but enriched Enterobacteriaceae, Citrobacter, and Gordonia. Both interventions decreased OSDI scores (Wilcoxon signed rank test, P < 0.05), but there was no significant difference between interventions (Mann-Whitney U, P = 0.54)., Conclusions: Carboxymethylcellulose artificial tears increased Actinobacteriota but decreased Bacteroides and Firmicutes bacteria. Carboxymethylcellulose artificial tears do not affect ocular surface microbiome diversity and are not significantly more effective than polyethylene glycol artificial tears for dry eye treatment., Translational Relevance: The 16S microbiome analysis has revealed small changes in the ocular surface microbiome associated with artificial tear use.

Nirmatrelvir (coadministered with ritonavir as PAXLOVID TM ) reduces the risk of COVID-19-related hospitalizations and all-cause death in individuals with mild-to-moderate COVID-19 at high risk of progression to severe disease. Ritonavir is coadministered as a pharmacokinetic enhancer. However, ritonavir may cause drug-drug interactions (DDIs) due to its interactions with various drug-metabolizing enzymes and transporters, including cytochrome P450 (CYP) 3A, CYP2D6, and P-glycoprotein transporters. To better understand the extent of DDIs (or lack thereof) of nirmatrelvir; ritonavir in a clinical setting, this study used real-world evidence (RWE) from the Optum Clinformatics Data Mart database to identify the top 100 drugs most commonly prescribed to US patients at high risk of progression to severe COVID-19 disease. The top 100 drugs were identified based on total counts associated with drugs prescribed to high-risk patients (i.e.,  ≥ 1 medical condition associated with an increased risk of severe COVID-19) who were continuously enrolled in the database throughout 2019 and had  ≥ 1 prescription claim. Each of the 100 drugs was then assessed for DDI risk based on their metabolism, excretion, and transport pathways identified from available US prescribing and medical literature sources. Seventy drugs identified were not expected to have DDIs with nirmatrelvir; ritonavir, including many cardiovascular agents, anti-infectives, antidiabetic agents, and antidepressants. Conversely, 30 drugs, including corticosteroids, narcotic analgesics, anticoagulants, statins, and sedatives/hypnotics, were expected to cause DDIs with nirmatrelvir; ritonavir. This RWE analysis is complementary to the prescribing information and other DDI management tools for guiding healthcare providers in managing DDIs., (© 2023. The Author(s).)

Citrus species among the most important and widely consumed fruit in the world due to Vitamin C, essential oil glands, and flavonoids. Highly variable simple sequence repeats (SSR) markers are one of the most informative and versatile molecular markers used in perennial tree genetic research. SSR survey of Citrus sinensis and Citrus maxima were identified perfect SSRs spanning nine chromosomes. Furthermore, we categorized all SSR motifs into three major classes based on their tract lengths. We designed and validated a class I SSRs in the C. sinensis and C. maxima genome through electronic polymerase chain reaction (ePCR) and found 83.89% in C. sinensis and 78.52% in C. maxima SSRs producing a single amplicon. Then, we selected extremely variable SSRs (> 40 nt) from the ePCR-verified class I SSRs and in silico validated across seven draft genomes of citrus, which provided us a subset of 84.74% in C. sinensis and 77.53% in C. maxima highly polymorphic SSRs. Out of these, 129 primers were validated on 24 citrus genotypes through wet-lab experiment. We found 127 (98.45%) polymorphic HvSSRs on 24 genotypes. The utility of the developed HvSSRs was demonstrated by analysing genetic diversity of 181 citrus genotypes using 17 HvSSRs spanning nine citrus chromosomes and were divided into 11 main groups through 17 HvSSRs. These chromosome-specific SSRs will serve as a powerful genomic tool used for future QTL mapping, molecular breeding, investigation of population genetic diversity, comparative mapping, and evolutionary studies among citrus and other relative genera/species., (© 2023. The Author(s).)

Extracellular vesicles (EVs) are membrane-bound nanoparticles released by cells and are an important means of intercellular communication in physiological and pathological states. We provide an overview of recent advances in the understanding of EV biogenesis, cargo selection, recipient cell effects, and key considerations in isolation and characterization techniques. Studies on the physiological role of EVs have relied on cell-based model systems due to technical limitations of studying endogenous nanoparticles in vivo . Several recent studies have elucidated the mechanistic role of EVs in liver diseases, including nonalcoholic fatty liver disease, viral hepatitis, cholestatic liver disease, alcohol-associated liver disease, acute liver injury, and liver cancers. Employing disease models and human samples, the biogenesis of lipotoxic EVs downstream of endoplasmic reticulum stress and microvesicles via intracellular activation stress signaling are discussed in detail. The diverse cargoes of EVs including proteins, lipids, and nucleic acids can be enriched in a disease-specific manner. By carrying diverse cargo, EVs can directly confer pathogenic potential, for example, recruitment and activation of monocyte-derived macrophages in NASH and tumorigenicity and chemoresistance in hepatocellular carcinoma. We discuss the pathogenic role of EVs cargoes and the signaling pathways activated by EVs in recipient cells. We review the literature that EVs can serve as biomarkers in hepatobiliary diseases. Further, we describe novel approaches to engineer EVs to deliver regulatory signals to specific cell types, and thus use them as therapeutic shuttles in liver diseases. Lastly, we identify key lacunae and future directions in this promising field of discovery and development. © 2023 American Physiological Society. Compr Physiol 13:4631-4658, 2023., (Copyright © 2023 American Physiological Society. All rights reserved.)

Finger millet is a key food security crop widely grown in eastern Africa, India and Nepal. Long considered a 'poor man's crop', finger millet has regained attention over the past decade for its climate resilience and the nutritional qualities of its grain. To bring finger millet breeding into the 21 st century, here we present the assembly and annotation of a chromosome-scale reference genome. We show that this ~1.3 million years old allotetraploid has a high level of homoeologous gene retention and lacks subgenome dominance. Population structure is mainly driven by the differential presence of large wild segments in the pericentromeric regions of several chromosomes. Trait mapping, followed by variant analysis of gene candidates, reveals that loss of purple coloration of anthers and stigma is associated with loss-of-function mutations in the finger millet orthologs of the maize R1/B1 and Arabidopsis GL3/EGL3 anthocyanin regulatory genes. Proanthocyanidin production in seed is not affected by these gene knockouts., (© 2023. The Author(s).)

Smoking accelerates periodontal disease and alters the subgingival microbiome. However, the relationship between smoking-associated subgingival dysbiosis and progression of periodontal disease is not well understood. Here, we sampled 233 subgingival sites longitudinally from 8 smokers and 9 non-smokers over 6-12 months, analyzing 804 subgingival plaque samples using 16 rRNA sequencing. At equal probing depths, the microbial richness and diversity of the subgingival microbiome was higher in smokers compared to non-smokers, but these differences decreased as probing depths increased. The overall subgingival microbiome of smokers differed significantly from non-smokers at equal probing depths, which was characterized by colonization of novel minority microbes and a shift in abundant members of the microbiome to resemble periodontally diseased communities enriched with pathogenic bacteria. Temporal analysis showed that microbiome in shallow sites were less stable than deeper sites, but temporal stability of the microbiome was not significantly affected by smoking status or scaling and root planing. We identified 7 taxa-Olsenella sp., Streptococcus cristatus, Streptococcus pneumoniae, Streptococcus parasanguinis, Prevotella sp., Alloprevotella sp., and a Bacteroidales sp. that were significantly associated with progression of periodontal disease. Taken together, these results suggest that subgingival dysbiosis in smokers precedes clinical signs of periodontal disease, and support the hypothesis that smoking accelerates subgingival dysbiosis to facilitate periodontal disease progression., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Flowering is a complex developmental process, with physiological and morphological phases influenced by a variety of external and internal factors. Interestingly, many mango cultivars tend to bear fruit biennially because of irregular flowering, and this has a negative impact on mango flowering and the subsequent yield, resulting in significant economic losses. In this article, transcriptome analysis was carried out on four tissues of mango cv. Dashehari (bearing tree leaf, shoot apex, inflorescence, and non-bearing tree leaf). De novo transcriptome assembly of RNA-seq reads of Dashehari using the Trinity pipeline generated 67,915 transcripts, with 25,776 genes identified. 85 flowering genes, represented by 179 transcripts, were differentially expressed in bearing vs. non-bearing leaf tissues. Gene set enrichment analysis of flowering genes identified significant upregulation of flowering related genes in inflorescence tissues compared to bearing leaf tissues. The flowering genes FT , CO , GI , ELF 4 , FLD , FCA , AP 1, LHY , and SCO1 were upregulated in the bearing leaf tissues. Pathway analysis of DEGs showed significant upregulation of phenylpropanoid and sucrose and starch pathways in non-bearing leaf tissue compared with bearing leaf tissue. The comparative transcriptome analysis performed in this study significantly increases the understanding of the molecular mechanisms driving the flowering process as well as alternative bearing in mango., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kaur, Sidhu, Mittal, Yadav, Mittal, Singla, Singh and Chhuneja.)

Modern plant breeding programs rely heavily on the generation of homozygous lines, with the traditional process requiring the inbreeding of a heterozygous cross for five to six generations. Doubled haploid (DH) technology, a process of generating haploid plants from an initial heterozygote, followed by chromosome doubling, reduces the process to two generations. Currently established in vitro methods of haploid induction include androgenesis and gynogenesis, while in vivo methods are based on uni-parental genome elimination. Parthenogenesis, embryogenesis from unfertilized egg cells, presents another potential method of haploid induction. PsASGR-BABY BOOM-like, an AP2 transcription factor, induces parthenogenesis in a natural apomictic species, Pennisetum squamulatum (Cenchrus squamulatus) and PsASGR-BBML transgenes promote parthenogenesis in several crop plants, including rice, maize, and pearl millet. The dominant nature of PsASGR-BBML transgenes impedes their use in DH technology. Using a glucocorticoid-based post-translational regulation system and watering with a 100 μM DEX solution before anthesis, PsASGR-BBML can be regulated at the flowering stage to promote parthenogenesis. Conditional expression presents a novel opportunity to use parthenogenetic genes in DH production technology and to elucidate the molecular mechanism underlying parthenogenetic embryogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sidhu, Conner and Ozias-Akins.)

Background & Aims: Retreatment with glecaprevir/pibrentasvir (G/P) resulted in a rate of sustained virologic response 12 weeks after treatment completion (SVR12) of >90% in HCV genotype 1 (GT1) patients who previously failed a regimen of sofosbuvir plus an NS5A inhibitor (NS5Ai). This study investigated the prevalence and impact of baseline NS3 and NS5A resistance-associated substitutions (RASs) on the efficacy of G/P in prior GT1 sofosbuvir+NS5Ai failures and the persistence of treatment-emergent RASs., Methods: Longitudinal samples from 177 patients enrolled in a phase IIIb, randomized pragmatic clinical trial were analyzed. Patients without cirrhosis were randomized to 12 or 16 weeks of G/P, and patients with compensated cirrhosis were randomized to G/P and ribavirin for 12 weeks or G/P for 16 weeks. Linkage of RAS was identified using Primer-ID next-generation sequencing at a 15% cut-off., Results: Of 177 patients, 169 (95.5%) were PI-naïve. All 33 GT1b-infected patients achieved SVR12. In GT1a-infected patients, baseline NS5A RASs were prevalent (74.5%, 105/141) but NS3 RASs were uncommon. Baseline NS3 RASs had no impact on G/P efficacy and patients with baseline NS5A RASs showed a numerically but not statistically significantly lower SVR12 rate compared to those without NS5A RASs (89% vs. 97%). SVR12 was achieved in 34 of 35 (97%) patients without NS5A baseline substitution, and 53 of 57 (93%), 35 of 40 (88%), 5 of 8 (63%) with single, double-linked, and triple-linked NS5A substitutions, respectively. Among 13 patients with virologic failure, 4 acquired treatment-emergent NS3 RASs and 10 acquired NS5A RASs., Conclusion: Baseline NS5A RASs were highly prevalent. The presence of an increasing number of linked NS5A RASs in GT1a showed a trend in decreasing SVR12 rates, although no specific NS5A RASs or their linkage pattern were associated with lower SVR12 rates., Lay Summary: Direct-acting antivirals have revolutionized the treatment of chronic hepatitis C infection, but treatment failure occurs in some patients. Retreatment of patients who previously failed a regimen consisting of sofosbuvir and an NS5A inhibitor with a regimen of glecaprevir and pibrentasvir (G/P) is >90% effective. Herein, we analyzed samples from these patients and showed that retreatment efficacy with G/P is lower in patients with double- or triple-linked NS5A resistance mutations than in patients with single or no NS5A resistance mutations., Clinical Trial Number: NCT03092375., Competing Interests: Conflict of interest Gary Wang: Has a patent issued. Gretja Schnell: Personal fees from AbbVie, during the conduct of the study; Personal Fees and other from AbbVie, outside the submitted work. Jens Kort: Personal fees from AbbVie; Personal fees and other from AbbVie, outside the submitted work; has a patent issued. Gurjit Sidhu: Nothing to disclose. Layla Schuster: Nothing to disclose. Rakesh Tripathi: Personal fees and other from AbbVie, outside the submitted work. Lois Larsen: Personal fees from AbbVie, during the conduct of the study; Personal Fees and other from AbbVie, outside the submitted work. Larry Michael: Nothing to disclose. Ken Bergquist: Nothing to disclose. Ashley Magee: Nothing to disclose. Chandni Patel: Nothing to disclose. Joan Whitlock: Nothing to disclose. Joy Peter: Domestic Partner is an AbbVie Stockholder. Michael Fried: Grants from AbbVie, Bristol-Myers Squibb, Merck, and Gilead; Personal Fees from AbbVie, Bristol-Myers Squibb, Merck, Roche; Personal fees and other from TARGET PharmaSolutions, outside the submitted work. David Nelson: Grants from AbbVie, Gilead and Merck during the conduct of the study; Stockholder of TARGET PharmaSolutions, outside the submitted work. Please refer to the accompanying ICMJE disclosure forms for further details., (Published by Elsevier B.V.)

Background: Bariatric surgery may improve heart failure outcome in morbidly obese patients. However, the safety of bariatric surgery has not been investigated in morbidly obese patients hospitalized for heart failure. We evaluated the effects of bariatric surgery on parameters of hospitalization for heart failure in morbidly obese patients., Methods: We analyzed administrative discharge data of morbidly obese patients with heart failure as a primary diagnosis. Propensity score matching was performed to assess parameters of hospitalization in morbidly obese patients with and without a history of bariatric surgery. The discharges with diastolic heart failure codes were analyzed separately., Results: Morbid obesity was coded in 4.4% of all discharges. Heart failure was the primary diagnosis in 6.0% of discharges with morbid obesity codes. Only 1% of discharges with morbid obesity and heart failure as primary diagnosis codes were coded for bariatric surgery. Length of stay (p < 0.001), in-hospital mortality (p < 0.001), and the estimated cost of hospitalizations (p < 0.007) were lower in discharges with than without bariatric surgery codes. Length of stay was shorter and in-hospital mortality was lower in discharges with codes for diastolic heart failure and bariatric surgery than with codes for only diastolic heart failure (p < 0.042 and p < 0.001 respectively)., Conclusion: When hospitalized for heart failure, morbidly obese patients who underwent bariatric surgery fare as well as or slightly better than their counterparts who did not.

Introduction: The pattern of atherosclerotic cardiovascular disease (ASCVD) and diabetes driven hospitalizations in the United States (U.S.) is unclear. We attempted to identify the disparate outcome in race related ASCVD hospitalizations with comorbid diabetes., Methods: Adults aged ≥40 years old with ASCVD (acute coronary syndrome (ACS), coronary artery disease (CAD), stroke, or peripheral arterial disease (PAD)) as the first-listed diagnosis with comorbid diabetes as a secondary diagnosis were determined using the U.S. 2005-2015 National (Nationwide) Inpatient Sample (NIS) data. The incidence of other modifiable cardiovascular risk factors (hypertension, dyslipidemia, smoking/substance abuse, obesity, and renal failure), in hospital procedures and outcomes was estimated. Complex samples multivariate regression was used to determine the odds ratio (OR) with 95% confidence Interval (CI) of risk associations and to determine patient comorbidity adjusted ASCVD related in-hospital mortality rate., Results: The rate of total ASCVD hospitalizations with comorbid diabetes adjusted to the U.S. census population increased by 5.7% for black men compared to 4% for black women. There was a higher odd of an ASCVD hospitalization if there was comorbid hypertension (Odds Ratio (OR 1.29; 95% CI 95% 1.28-1.31), dyslipidemia (OR 2.03; 95% CI 2.01-2.05), renal failure (OR 1.84; 95% CI 1.82-1.86), and smoking/substance use disorder (OR 1.31; 95% CI 1.29-1.33). White Women had the highest risk-adjusted incidence of ASCVD related in-hospital mortality (4.2%) relative to black women (3.9%), compared to white men (3.6%) and black men (3.5%) respectively., Conclusions: Despite improving treatment options for ASCVD in the diabetic population, blacks with diabetes continue to have a higher hospitalization burden with a concomitant disparity in comorbid presentation and outcome. Further evaluation is the need to understand these associations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V.)

Background and Aims: Hemospray is a non-contact modality of endoscopic hemostasis that has been used in the management of upper gastrointestinal bleeding (UGIB) with varying success. Our aim was to evaluate the efficacy of Hemospray in the management of UGIB., Methods: An electronic bibliographic search of digital dissertation databases was performed from inception till October 2019. All prospective studies, including randomized controlled trials evaluating the efficacy of Hemospray in the management of UGIB were analysed. The primary outcome was immediate haemostasis and the secondary outcome was rebleeding rate. Subgroup analyses based on etiology of UGIB (tumour-related, variceal, etc) were also performed., Results: A total of 11 prospective studies, including 4 randomized trials were included for the analysis. The pooled immediate haemostasis rate with Hemospray was 93% (95% CI 90.3-95%, p<0.001). Rebleeding occurred in 14.4% (95% CI 8.8-22.8%, p<0.001) of patients. For the subgroup of tumour-related bleeding, the immediate haemostasis rate was 95.3% (95% CI 89.6-97.3%; p <0.001) and rebleeding rate was 21.9% (95% CI 13.9-32.7%, p <0.001). In patients with variceal bleeding, immediate haemostasis was achieved in 92.7% (95% CI 83.6-96.9%; p<0.001) of patients, with a rebleeding rate of 3.1% (95% CI 0.9-10.2%, p <0.001)., Conclusion: Hemospray shows high immediate haemostasis and low bleeding percentages. The odds were in its favour compared to conventional endoscopic modalities, but not statistically significant. The results are undermined by the risk of bias in the studies. Nevertheless, it is an easy technique that should be further investigated with better studies.

Background: Depression is the most common mental health condition affecting perinatal women and mothers worldwide. Worldwide, about 10% of pregnant women and 13% of women who have given birth experience a mental disorder, primarily depression. In developing countries like India, this is even higher, i.e., 15.6% during pregnancy and 19.8% after childbirth. The present study was initiated with the objective of studying the prevalence of depression among women in the peripartum period and to find the association of peripartum depression and its risk factors., Materials and Methods: This was a hospital-based cross-sectional study, including mothers in antenatal and postnatal period. A sample size of 200 was calculated using Daniels' formula. A questionnaire was administered by the investigator in vernacular language by an interview technique for assessing awareness and behavior of all participants. The Edinburgh Postnatal Depression Scale was used to identify the patients at the risk of depression. Written informed consent was taken from every participant., Results: The prevalence of peripartum depression was 14%. Younger age group (not <18 years), working female, joint family, first pregnancy, social support from in-laws, and not having desire/pressure for a male child were found to be associated with a lower prevalence of peripartum depression. Other variables which were not significantly associated with peripartum depression were education of the participants and their husbands and urban/rural locality., Conclusion: The prevalence of peripartum depression is quite high and is negatively associated with first pregnancy, joint family, and working status., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 International Journal of Applied and Basic Medical Research.)

Kinnow mandarin ( Citrus reticulata Blanco) is a popular citrus crop of northwestern India and it occupies maximum fruit area in Punjab. However, citrus juice processing industry is still suffering from delayed bitterness problem caused mainly by limonoid aglycones such as limonin. In order to study citrus limonoid metabolism, limonoid glucosyltransferase ( LGT ) gene, which encodes a natural debittering enzyme, was isolated from the fruit tissues of Kinnow mandarin. After confirmation and characterization, its full-length gene sequence (1533 bp) was submitted to National Centre for Biotechnology Information. Citrus reticulata limonoid glucosyltransferase ( CrLGT ) occupies a position on an independent branch in the largest subgroup and is phylogenetically different from those in other mandarin species like C. unshiu, showing its uniqueness in several features. The transcript expression of CrLGT , evaluated in different tissues such as young leaf, flavedo, albedo, sac covering and seed of Kinnow mandarin during early (90 days after flowering (DAF)), mid (150-210 DAF) and late (240 DAF) fruit developmental stages using semi-quantitative method, showed the highest expression in flavedo. Thus, it was concluded that the isolated LGT gene has an effect on limonoid metabolic engineering in citrus. Overexpression of this gene can reduce the delayed bitterness problem in citrus juice and enhance the accumulation of specific glucosides that have anticancer effects., Competing Interests: CONFLICT OF INTEREST: All authors have no conflict of interest to declare for this manuscript.

Malignant pleural mesotheliomas (MPM) are most often surgically unresectable, and they respond poorly to current chemotherapy and radiation therapy. Between 23 and 64% of malignant pleural mesothelioma have somatic inactivating mutations in the BAP1 gene. BAP1 is a homologous recombination (HR) DNA repair component found in the BRCA1/BARD1 complex. Similar to BRCA1/2 deficient cancers, mutation in the BAP1 gene leads to a deficient HR pathway and increases the reliance on other DNA repair pathways. We hypothesized that BAP1-mutant MPM would require PARP1 for survival, similar to the BRCA1/2 mutant breast and ovarian cancers. Therefore, we used the clinical PARP1 inhibitors niraparib and olaparib to assess whether they could induce synthetic lethality in MPM. Surprisingly, we found that all MPM cell lines examined, regardless of BAP1 status, were addicted to PARP1-mediated DNA repair for survival. We found that niraparib and olaparib exposure markedly decreased clonal survival in multiple MPM cell lines, with and without BAP1 mutations. This clonal cell death may be due to the extensive replication fork collapse and genomic instability that PARP1 inhibition induces in MPM cells. The requirement of MPM cells for PARP1 suggests that they may generally arise from defects in HR DNA repair. More importantly, these data demonstrate that the PARP1 inhibitors could be effective in the treatment of MPM, for which little effective therapy exists.

Aim: The aim of this systematic review is to evaluate the efficacy and safety of rifaximin in the prophylaxis of spontaneous bacterial peritonitis (SBP) as compared with norfloxacin., Methods: We searched MEDLINE, CINAHL, Google Scholar and Cochrane databases from inception to January 2017. Reference lists of articles as well as conference proceedings were manually screened. We included studies that recruited patients with cirrhosis and ascites who met the criteria for primary or secondary SBP prophylaxis as defined by the European Association for the Study of the Liver and American Association for the Study of Liver Diseases. Two independent investigators reviewed the studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was occurrence of SBP. Secondary outcomes included mortality and adverse events with therapy., Results: Of the 435 studies identified, a total of five were included for full-text review. Four studies were eligible for the systematic review, three of which were randomised controlled trials and one was a prospective observational study. The population examined in majority of studies was primarily hepatitis C cirrhosis. The results of individual studies indicated either superior efficacy of rifaximin or no statistical difference between rifaximin and norfloxacin for SBP prophylaxis., Conclusions: Moderate-quality evidence shows that long-term use of rifaximin appears to be a reasonable alternative to norfloxacin for SBP prevention in hepatitis C cirrhosis.

Replication is not as continuous as once thought, with DNA damage frequently stalling replication forks. Aberrant repair of stressed replication forks can result in cell death or genome instability and resulting transformation to malignancy. Stressed replication forks are most commonly repaired via homologous recombination (HR), which begins with 5' end resection, mediated by exonuclease complexes, one of which contains Exo1. However, Exo1 requires free 5'-DNA ends upon which to act, and these are not commonly present in non-reversed stalled replication forks. To generate a free 5' end, stalled replication forks must therefore be cleaved. Although several candidate endonucleases have been implicated in cleavage of stalled replication forks to permit end resection, the identity of such an endonuclease remains elusive. Here we show that the 5'-endonuclease EEPD1 cleaves replication forks at the junction between the lagging parental strand and the unreplicated DNA parental double strands. This cleavage creates the structure that Exo1 requires for 5' end resection and HR initiation. We observed that EEPD1 and Exo1 interact constitutively, and Exo1 repairs stalled replication forks poorly without EEPD1. Thus, EEPD1 performs a gatekeeper function for replication fork repair by mediating the fork cleavage that permits initiation of HR-mediated repair and restart of stressed forks., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Study Design: Retrospective case series., Objective: To identify specific magnetic resonance imaging (MRI) characteristics of epidural fluid collections associated with infection, hematoma, or cerebrospinal fluid (CSF)., Summary of Background Data: Interpretation of postoperative MRI can be challenging after lumbar fusion. The purpose of this study was to identify specific MRI characteristics of epidural fluid collections associated with infection, hematoma, or CSF., Methods: The study population includes consecutive patients between 2006 and 2010 who had MRIs performed within 2 weeks after elective surgery for evaluation of possible CSF fluid collection, hematoma, or infection. Patients with known previous infection (discitis/osteomyelitis) or inadequate MRIs were excluded from the study. Medical records were reviewed to determine the diagnosis (infection, hematoma, or pseudomeningocele) underlying the fluid collection. MRIs were retrospectively evaluated by a musculoskeletal radiologist and orthopedic spine attending who were blinded to the pathologic diagnosis for characteristics of the fluid collection. MRI characteristics include location of lesion: osseous involvement, disk location, anterior versus posterior versus anteroposterior, soft-tissue involvement, and iliopsoas involvement. Characteristics of the lesion include: volume of lesion, loculation, satellite lesions, multiple loci, destructive characteristics, and mass effect upon thecal sac. Enhancement was scored based upon the following variables: rim enhancement, smooth versus irregular, thin versus thick, heterogeneity, diffuse enhancement, nonenhancement, and rim thickness. General fluid collection intensity and complexity on T1, T2, and T1 postcontrast images was scored as high, medium, and low. The χ test was used to compare the incidence of imaging characteristics between patient groups (infection, hematoma, and CSF)., Results: Thirty-three patients were identified who met inclusion criteria. There were 13 (39%) with infection, 9 (27%) with hematoma, and 11 (33%) with CSF collection. Factors that were associated with infection were osseous involvement (R=0.392, P=0.024) and destructive characteristics (R=0.461, P=0.007). Factors that were correlated with hematoma include mass effect (R=0.515, P=0.002) and high T1-signal intensity (R=0.411, P=0.019), absence of thecal sac communication (R=-0.389, P=0.025), and absence of disk involvement (R=-0.346, P=0.048). Pseudomeningocele was associated with thecal sac communication (R=0.404, P=0.02), absence of mass effect (R=-0.48, P=0.005), low T1 signal (R=-0.364, P=0.04), and low T2 complexity (R=-0.479, P=0.005)., Conclusion: Specific characteristics of the postoperative MRI can be used to distinguish infection from noninfectious fluid collections. The strongest predictors of infection were osseous involvement and destructive bony changes. Hematoma was associated with mass effect on the thecal sac, high T1-signal intensity, and absence of thecal sac communication and disk involvement. CSF collections were distinguished by absence of mass effect, low T2-signal complexity, low T1-signal intensity, and communication with the thecal sac.

Study Design: Systematic review., Objective: To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI)., Methods: A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained., Results: The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood., Conclusion: Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI.

Study Design: Retrospective analysis of a prospective cohort., Objective: Change in cervical angular alignment may be associated with dysphagia., Summary of Background Data: Bony deformities of the cervical spine may be associated with secondary contractures of soft tissues in the neck. Acute surgical deformity correction causes in changes in soft tissue tension in the anterior neck, resulting in dysphagia., Methods: The study population included patients undergoing 1 and 2 level elective anterior cervical discectomy and fusion for cervical myelopathy or radiculopathy. Preoperative and postoperative radiographs at 2 weeks were measured by a blinded observer for C2-C7 endplate angle, C2-C7 posterior vertebral body length, and occipital condyle plumb line distance on upright lateral radiographs at 2, 6, and 12 weeks postoperatively. Patients were prospectively queried about dysphagia incidence and severity using a numeric rating scale. Multiple linear regression analysis was used to determine the effect of change in radiographic parameters controlling for demographic characteristics., Results: The study population included 25 patients with complete radiographs. The mean change in C2-C7 angle was -0.6 degrees (SD 9), the mean change in C2-C7 length was 1.7 mm (SD 26), the mean change in occipital condyle plumb line distance was 2.3 mm (SD 20).Multiple linear regression analysis was performed including operative time, age, sex, number of levels, and change in radiographic parameters as independent variables and using dysphagia score as the dependent variable. The change in C2-C7 angle and operative time were the only statistically significant predictors of change in dysphagia at 2 and 6 weeks postoperatively., Conclusions: These results indicate that lordotic change in spinal alignment and longer operative times are associated with increased postoperative dysphagia. Surgeons should counsel patients in whom a large angular correction is expected about the possibility for postoperative dysphagia. Furthermore, future studies on dysphagia incidence should include radiographic alignment as an independent predictor of dysphagia.

Geriatric hip fractures are a challenging clinical problem throughout the world. Hip fracture services have been shown to shorten time to surgery, decrease the cost of admissions, and improve the outcomes. We instituted a geriatric hip fracture program for comanagement of these injuries by orthopedic and internal medicine teams at our hospital in India. From January 2010 till December 2011, 119 patients with a femoral neck fracture were treated with cemented modular hemiarthroplasty under this program using a cost-effective Indian implant. The cohort included 63 males and 56 females with a mean age of 70.7 years (range 55-98 years). Hypertension (n = 42) and diabetes mellitus (n = 29) were the most common comorbidities. The follow-up period ranged from 12 to 37 months with an average of 24 months. The surgery was performed within 24 hours of admission in 60.5% (n = 72) patients. The use of antiplatelet drugs was the most common reason for delay of surgery. The mean length of hospital stay was 10.4 days (range 3-24 days) with 77% (n = 92) of patients discharged within 1 week of admission. On follow-up, good to excellent Harris hip scores were seen in 88% of patients with 76% of patients returning to the preinjury ambulatory status. The mortality rate was 6% at 6 months follow-up and 10.9% at 2 years. Our study shows that a hip fracture program can be instituted in India. The program helped us in achieving the goal of early surgery, mobilization, and discharge from hospital with decreased mortality.

Background: Although conventional open posterior lumbar interbody fusion (open PLIF) is efficacious in management of lumbar spinal instability, concerns exist regarding lengthy hospital stays, blood loss, and postoperative complications. Minimally invasive posterior lumbar interbody fusion (MIS PLIF) may be able to address these concerns, but the research on this topic has not been systematically reviewed., Questions/purposes: We performed a systematic review to determine whether MIS PLIF or open PLIF results in (1) better perioperative parameters, including blood loss, operative times, and length of hospital stay; (2) improved patient-reported outcome scores; and (3) improved disc distraction and (4) frequency of reoperation and complications when compared with open PLIF procedures., Methods: A literature search of the MEDLINE database identified seven studies that met our inclusion criteria. A total of seven articles were included; quality was assessed using the Methodological Index for Non-Randomised Studies (MINORS) scale. Descriptive statistics were used to describe the included articles., Results: In most studies, MIS PLIF was associated with decreased blood loss and shorter hospital stay but longer operative times. MIS PLIF resulted in better patient-related outcomes when compared with open PLIF in two studies in the short term, but most of the studies in this review found no short-term differences, and there was no difference at long-term followup in any studies. There was no significant difference in disc distraction. Both techniques appeared to have similar complication rates and reoperation rates., Conclusions: Based on the available evidence, which we restricted to prospective and retrospective studies with control groups, but did not include any well-designed randomized trials, MIS PLIF might lead to better perioperative parameters, but there was little evidence for improved patient-reported outcomes in the MIS groups. Randomized controlled trials are needed to compare these two surgical techniques.

Study Design: A biomechanical study., Objective: To test the mechanical and physical properties of self-reinforced copolymer bioresorbable posterior cervical rods and compare their mechanical properties to commonly used Irene titanium alloy rods., Summary of Background Data: Bioresorbable instrumentation is becoming increasingly common in surgical spine procedures. Compared with metallic implants, bioresorbable implants are gradually reabsorbed as the bone heals, transferring the load from the instrumentation to bone, eliminating the need for hardware removal. In addition, bioresorbable implants produce less stress shielding due to a more physiological modulus of elasticity., Methods: Three types of rods were used: (1) 5.5 mm copolymer rods and (2) 3.5 mm and (3) 5.5 mm titanium alloy rods. Four tests were used on each rod: (1) 3-point bending test, (2) 4-point bending test, (3) shear test, and (4) differential scanning calorimeter test. The outcomes were recorded: Young modulus (E), stiffness, maximum load, deflection at maximum load, load at 1.0% strain of the rod's outer surface, and maximum bending stress., Results: The Young modulus (E) for the copolymer rods (mean range, 6.4-6.8 GPa) was significantly lower than the 3.5 mm titanium rods (106 GPa) and the 5.5 mm titanium rods (95 GPa). The stiffness of the copolymer rods (mean range, 16.6-21.4 N/mm) was also significantly lower than the 3.5 mm titanium alloy rods (43.6 N/mm) and the 5.5 mm titanium alloy rods (239.6 N/mm). The mean maximum shear load of the copolymer rods was 2735 N and they had significantly lower mean maximum loads than the titanium rods., Conclusions: Copolymer rods have adequate shear resistance, but less load resistance and stiffness compared with titanium rods. Their stiffness is closer to that of bone, causing less stress shielding and better gradual dynamic loading. Their use in semirigid posterior stabilization of the cervical spine may be considered.

Background: The principles that guide management of spinal cord injury (SCI) derive from injury resulting from blunt trauma, not gunshot wounds. Civilian gunshot-induced spinal cord injury (CGSWSCI) is a common, potentially serious cause of neurological deficit; there is disagreement about whether the same approaches used for SCI caused by blunt-force trauma should apply to gunshot-induced SCI., Questions/purposes: We reviewed the literature to answer the following questions regarding presentation and outcome of gunshot wound-induced SCI: (1) Are there differences in recovery prognosis between complete SCI and other patterns of SCI in CGSWSCI. (2) Does the use of steroids improve neurological recovery? (3) Does surgery to remove the bullet affect neurological recovery in CGSWSCI? (4) Does surgery result in an increased risk of complications of treatment?, Methods: We performed a systematic literature review of articles related to civilian gunshot injuries to the spine. Information relating to incidence, pattern of neurological injury, associated injuries, treatment, neurological outcome, and associated complications was extracted. Three independent reviewers assessed the strength of evidence present in the literature by examining quality, quantity, and consistency of results., Results: A total of 15 articles met the predetermined inclusion criteria. Complete SCIs are associated with the worst functional recovery regardless of treatment. Steroids do not appear to have any added benefit in terms of restoring sensory and motor function. There appears to be some neurologic benefit to surgical decompression with intracanalicular bullet retrieval in patients with an incomplete lesion and a cauda equina syndrome. Complication rates are greater in operated patients., Conclusions: These findings should be interpreted with caution because of considerable heterogeneity among the studies in the literature on gunshot-induced SCI and because of generally poor-quality study design and a high associated risk of selection bias. Supportive management should be the primary method of care, whereas surgery should be an option in case of radiographic evidence of a static compression on the spinal cord. Future studies are necessary to develop better treatment guidelines for patients with gunshot wound-associated SCI.

Background Context: Adjacent segment disease (ASD) is symptomatic deterioration of spinal levels adjacent to the site of a previous fusion. A critical issue related to ASD is whether deterioration of spinal segments adjacent to a fusion is due to the spinal intervention or due to the natural history of spinal degenerative disease., Purpose: The purpose of this review is to summarize the recent clinical literature on adjacent segment disease in light of the natural history, patient-modifiable risk factors, surgical risk factors, sagittal balance, and new technology., Study Design: This review will evaluate the recent literature on genetic and hereditary components of spinal degenerative disease and potential links to the development of ASD., Methods: After a meticulous search of Medline for relevant articles pertaining to our review, we summarized the recent literature on the rate of ASD and the effect of various interventions, including motion preservation, sagittal imbalance, arthroplasty, and minimally invasive surgery., Results: The reported rate of ASD after decompression and stabilization procedures is approximately 2% to 3% per year. The factors that are consistently associated with adjacent segment disease include laminectomy adjacent to a fusion and a sagittal imbalance., Conclusions: Spinal surgical interventions have been associated with ASD. However, whether such interventions may lead to an acceleration of the natural history of the disease remains questionable., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The hypothesis of this study is that pelvic obliquity (PO) is associated with specific patterns of degenerative scoliosis., Methods: This study was a retrospective case series of consecutive patients undergoing fusion for lumbar conditions (degenerative scoliosis or spondylolisthesis). The discrepancy in the iliac crest height, coronal L1-S1 endplate angles, distance from L1 coronal bisector to the sacral center, number of degenerative scoliosis curves, and individual curve angulations were measured., Results: Limb length discrepancy was present in 87% of patients with a degenerative scoliosis. There were 116 patients with a single curve > 5° and PO > 2 cm. Of the patients with a single curve, the apex of scoliosis was opposite the high iliac crest side in 79% patients. There were 338 patients with a double curve. The apex of scoliosis was opposite the high iliac crest side in 48% of patients., Conclusion: There were distinct patterns of limb length discrepancy corresponding to degenerative scoliotic curve morphology. In patients with single degenerative scoliotic curves, PO most commonly appeared to counteract the scoliotic curve and result in an overall decrease in trunk shift. This occurred because the high iliac crest was observed most commonly on the convex side of the scoliotic curve. This effect was not observed in double lumbar degenerative scoliotic curves., (© 2013 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.)

The authors endeavor to highlight the surgical management of severe neurological deficit resulting from cement leakage after percutaneous vertebroplasty and to systematically review the literature on the management of this complication. A patient presented after a vertebroplasty procedure for traumatic injury. A CT scan showed polymethylmethacrylate leakage into the right foramina at T-11 and L-1 and associated central stenosis at L-1. He underwent decompression and fusion for removal of cement and stabilization of the fracture segment. In the authors' systematic review, they searched Medline, Scopus, and Cochrane databases to determine the overall number of reported cases of neurological deficit after cement leakage, and they collected data on symptom onset, clinical presentation, surgical management, and outcome. After surgery, despite neurological recovery postoperatively, the patient developed pneumonia and died 16 days after surgery. The literature review showed 21 cases of cement extravasation with neurological deficit. Ultimately, 15 patients had resolution of the postoperative deficit, 5 had limited change in neurological status, and 2 had no improvement. Cement augmentation procedures are relatively safe, but certain precautions should be taken to avoid such complications including high-resolution biplanar fluoroscopy, considering the use of a local anesthetic, and controlling the location of cement spread in relationship to the posterior vertebral body. Immediate surgical intervention with removal of cement provides good results with complete recovery in most cases.