Displaying publications 81 - 100 of 305 in total

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  1. Monitoring of heavy metal pollution in urban and rural environments across Pakistan using House crows (Corvus splendens) as bioindicator
    Iqbal F, Ayub Q, Wilson R, Song BK, Talei A, Yeong KY, et al.
    Environ Monit Assess, 2021 Mar 30;193(4):237.
    PMID: 33783594 DOI: 10.1007/s10661-021-08966-7
    A widely distributed urban bird, the house crow (Corvus splendens), was used to assess bioavailable heavy metals in urban and rural environments across Pakistan. Bioaccumulation of arsenic (As), zinc (Zn), lead (Pb), cadmium (Cd), nickel (Ni), iron (Fe), manganese (Mn), chromium (Cr), and copper (Cu) was investigated in wing feathers of 96 crows collected from eight locations and categorized into four groups pertaining to their geographical and environmental similarities. Results revealed that the concentrations of Pb, Ni, Mn, Cu, and Cr were positively correlated and varied significantly among the four groups. Zn, Fe, Cr, and Cu regarded as industrial outputs, were observed in birds both in industrialized cities and in adjoining rural agricultural areas irrigated through the Indus Basin Irrigation System. Birds in both urban regions accrued Pb more than the metal toxicity thresholds for birds. The house crow was ranked in the middle on the metal accumulation levels in feathers between highly accumulating raptor and piscivore and less contaminated insectivore and granivore species in the studied areas,. This study suggests that the house crow is an efficient bioindicator and supports the feasibility of using feathers to discriminate the local pollution differences among terrestrial environments having different levels and kinds of anthropogenic activities.
  2. Fulltext Description of Sarcocystis scandentiborneensis sp. nov. from treeshrews (Tupaia minor, T. tana) in northern Borneo with annotations on the utility of COI and 18S rDNA sequences for species delineation
    Ortega Pérez P, Wibbelt G, Brinkmann A, Galindo Puentes JA, Tuh FYY, Lakim MB, et al.
    Int J Parasitol Parasites Wildl, 2020 Aug;12:220-231.
    PMID: 32695576 DOI: 10.1016/j.ijppaw.2020.07.003
    Sarcocystis scandentiborneensis sp. nov. was discovered in histological sections of striated musculature of treeshrews (Tupaia minor, T. tana) from Northern Borneo. Sarcocysts were cigar-shaped, 102 μm-545 μm long, and on average 53 μm in diameter. The striated cyst wall varied in thickness (2-10 μm), depending on whether the finger-like, villous protrusions (VP) were bent. Ultrastructurally, sarcocysts were similar to wall type 12 but basal microtubules extended into VPs that tapered off with a unique U-shaped, electron-dense apical structure. In phylogenetic trees of the nuclear 18S rRNA gene, S. scandentiborneensis formed a distinct branch within a monophyletic subclade of Sarcocystis spp. with (colubrid) snake-rodent life cycle. We mapped all intraspecific (two haplotypes) and interspecific nucleotide substitutions to the secondary structure of the 18S rRNA gene: in both cases, the highest variability occurred within helices V2 and V4 but intraspecific variability mostly related to transitions, while transition/transversion ratios between S. scandentiborneensis, S. zuoi, and S. clethrionomyelaphis were skewed towards transversions. Lack of relevant sequences restricted phylogenetic analysis of the mitochondrial Cytochrome C oxidase subunit I (COI) gene to include only one species of Sarcocystis recovered from a snake host (S. pantherophisi) with which the new species formed a sister relationship. We confirm the presence of the functionally important elements of the COI barcode amino acid sequence of S. scandentiborneensis, whereby the frequency of functionally important amino acids (Alanine, Serine) was markedly different to other taxa of the Sarcocystidae. We regard S. scandentiborneensis a new species, highlighting that structurally or functionally important aspects of the 18S rRNA and COI could expand their utility for delineation of species. We also address the question why treeshrews, believed to be close to primates, carry a parasite that is genetically close to a Sarcocystis lineage preferably developing in the Rodentia as intermediate hosts.
  3. Fluid-structure interaction (FSI) modeling of bone marrow through trabecular bone structure under compression
    Rabiatul AAR, Fatihhi SJ, Md Saad AP, Zakaria Z, Harun MN, Kadir MRA, et al.
    Biomech Model Mechanobiol, 2021 Jun;20(3):957-968.
    PMID: 33547975 DOI: 10.1007/s10237-021-01423-x
    The present study has sought to investigate the fluid characteristic and mechanical properties of trabecular bone using fluid-structure interaction (FSI) approach under different trabecular bone orientations. This method imposed on trabecular bone structure at both longitudinal and transverse orientations to identify effects on shear stress, permeability, stiffness and stress regarded to the trabeculae. Sixteen FSI models were performed on different range trabecular cubes of 27 mm3 with eight models developed for each longitudinal and transverse direction. Results show that there was a moderate correlation between permeability and porosity, and surface area in the longitudinal and transverse orientations. For the longitudinal orientation, the permeability values varied between 3.66 × 10-8 and 1.9 × 10-7 and the sheer stress values varied between 0.05 and 1.8 Pa, whilst for the transverse orientation, the permeability values varied between 5.95 × 10-10 and 1.78 × 10-8 and the shear stress values varied between 0.04 and 3.1 Pa. Here, transverse orientation limits the fluid flow from passing through the trabeculae due to high shear stress disturbance generated within the trabecular bone region. Compared to physiological loading direction (longitudinal orientation), permeability is higher within the range known to trigger a response in bone cells. Additionally, shear stresses also increase with bone surface area. This study suggests the shear stress within bone marrow in real trabecular architecture could provide the mechanical signal to marrow cells that leads to bone anabolism and can depend on trabecular orientation.
  4. Fulltext Multi-assay investigation of viral etiology in pediatric central nervous system infections
    Altay-Kocak A, Bozdayi G, Michel J, Polat M, Kanik-Yuksek S, Tezer H, et al.
    J Infect Dev Ctries, 2020 06 30;14(6):572-579.
    PMID: 32683347 DOI: 10.3855/jidc.12327
    INTRODUCTION: In an attempt to identify a wide spectrum of viral infections, cerebrospinal fluid (CSF) specimens were collected from pediatric cases with the preliminary diagnosis of viral encephalitis/meningoencephalitis in two reference hospitals, from October 2011 to December 2015.

    METHODOLOGY: A combination of nucleic acid-based assays, including in house generic polymerase chain reaction (PCR) assays for enteroviruses, flaviviruses and phleboviruses, a commercial real-time PCR assay for herpesviruses and a commercial real time multiplex PCR, enabling detection of frequently-observed viral, bacterial and fungal agents were employed for screening.

    RESULTS: The microbial agent could be characterized in 10 (10%) of the 100 specimens. Viral etiology could be demonstrated in 7 (70%) specimens, which comprises Human Herpesvirus 6 (4/7), Herpes Simplex virus type1 (2/7) and Enteroviruses (1/7). In 3 specimens (30%), Streptococcus pneumoniae, Listeria monocytogenes and Staphylococcus aureus were detected via the multiplex PCR, which were also isolated in bacteriological media. All specimens with detectable viral nucleic acids, as well as unreactive specimens via nucleic acid testing remained negative in bacteriological cultures.

    CONCLUSIONS: Herpes and enteroviruses were identified as the primary causative agents of central nervous system infections in children. Enterovirus testing must be included in the diagnostic work-up of relevant cases.

  5. Fulltext Development of generic Asian pelvic bone models using CT-based 3D statistical modelling
    Ahrend MD, Noser H, Shanmugam R, Burr F, Kamer L, Kamarul T, et al.
    J Orthop Translat, 2020 Jan;20:100-106.
    PMID: 31908940 DOI: 10.1016/j.jot.2019.10.004
    Background/Objective: Artificial bone models (ABMs) are used in orthopaedics for research of biomechanics, development of implants and educational purposes. Most of the commercially available ABMs approximate the morphology of Europeans, but they may not depict the Asian anatomy. Therefore, our aim was to develop the first Asian ABM of the pelvis and compare it with the existing pelvic ABM (Synbone®; Caucasian male).

    Methods: One hundred clinical computed tomography (CTs) of adult pelvises (male n ​= ​50, female n ​= ​50) of Malay, Chinese and Indian descent were acquired. CTs were segmented and defined landmarks were placed. Three 3D statistical pelvic model and mean models (overall, male, female) were generated. Anatomical variations were analysed using principal component analysis. To measure gender-related differences and differences to the existing ABM, distances between the anterior superior iliac spines (ASIS), the anterior inferior iliac spines (AIIS), the promontory and the symphysis (conjugate vera, CV) as well as the ischial spines (diameter transversa, DT) were quantified.

    Results: Principal component analysis displayed large variability regarding the pelvic shape and size. Female and male statistical models were similar in ASIS (225 ​± ​20; 227 ​± ​13 ​mm; P ​= ​0.4153) and AIIS (185 ​± ​11; 187 ​± ​10 ​mm; P ​= ​0.3982) and differed in CV (116 ​± ​10; 105 ​± ​10 ​mm; P ​

  6. Fulltext Plasmon-Enhanced Biosensing for Multiplexed Profiling of Extracellular Vesicles
    Min J, Son T, Hong JS, Cheah PS, Wegemann A, Murlidharan K, et al.
    Adv Biosyst, 2020 12;4(12):e2000003.
    PMID: 32815321 DOI: 10.1002/adbi.202000003
    Extracellular vesicles (EVs)-nanoscale phospholipid vesicles secreted by cells-present new opportunities for molecular diagnosis from non-invasive liquid biopsies. Single EV protein analysis can be extremely valuable in studying EVs as circulating cancer biomarkers, but it is technically challenging due to weak detection signals associated with limited amounts of epitopes and small surface areas for antibody labeling. Here, a new, simple method that enables multiplexed analyses of EV markers with improved sensitivities is reported. Specifically, plasmon-enhanced fluorescence detection is implemented that amplifies fluorescence signals using surface plasmon resonances excited by periodic gold nanohole structures. It is shown that fluorescence signals in multiple channels are amplified by one order of magnitude, and both transmembrane and intravesicular markers can be detected at the single EV level. This approach can offer additional insight into understanding subtypes, heterogeneity, and production dynamics of EVs during disease development and progression.
  7. IPVS policy statement on HPV nucleic acid testing guidance for those utilising/considering HPV as primary precancer screening: Quality assurance and quality control issues
    Garland SM, Iftner T, Cuschieri K, Kaufmann AM, Arbyn M, de Sanjose S, et al.
    J Clin Virol, 2023 Feb;159:105349.
    PMID: 36584621 DOI: 10.1016/j.jcv.2022.105349
    We advise that only clinically validated HPV assays which have fulfilled internationally accepted performance criteria be used for primary cervical screening. Further, assays should be demonstrated to be fit for purpose in the laboratory in which they will ultimately be performed, and quality materials manuals and frameworks will be helpful in this endeavor. Importantly, there is a fundamental shortage of well validated, low-cost, low complexity HPV tests that have demonstrated utility in a near-patient setting; representing a significant challenge and focus for future development in order to reach the WHO's goal of eliminating cervical cancer.
  8. Fulltext In-situ preparation of CoFe2O4 nanoparticles on eggshell membrane-activated carbon for microwave absorption
    Soleimani H, Yusuf JY, Chuan LK, Soleimani H, Bin Sabar ML, Öchsner A, et al.
    Heliyon, 2023 Mar;9(3):e13256.
    PMID: 36851968 DOI: 10.1016/j.heliyon.2023.e13256
    This study explores the potential of using cobalt ferrite (CF) nanoparticles grown in situ on eggshell membranes (ESM) to mitigate the increasing problem of electromagnetic interference (EMI). A simple carbonization process was adopted to synthesize CF nanoparticles on ESM. The study further examines the composites' surface morphology and chemical composition and evaluates their microwave absorption performance (MAP) at X-band frequency. Results showed that the composite of CF and ESM - CESM@CF, exhibited a strong RL peak value of -39.03 mm with an optimal thickness of 1.5 mm. The combination of CF and ESM demonstrates excellent impedance matching and EM wave attenuation. The presence of numerous interfaces, conduction loss from the morphology, interfacial polarisation, and dual influence from both CF and ESM contribute to the high MAP of the composite. CESM@CF composite is projected as an excellent biomass-based nano-composite for EM wave absorption applications.
  9. Fulltext Recurrence Rates and Pharmacological Treatment for Hemorrhoidal Disease: A Systematic Review
    Lohsiriwat V, Sheikh P, Bandolon R, Ren DL, Roslani AC, Schaible K, et al.
    Adv Ther, 2023 Jan;40(1):117-132.
    PMID: 36331754 DOI: 10.1007/s12325-022-02351-7
    INTRODUCTION: Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence rate, there is a lack of understanding around interventions that can reduce recurrence and improve outcomes for patients. As such, a systematic literature review (SLR) was conducted to summarize evidence on epidemiology, recurrence, and efficacy of interventions in HD.

    METHODS: Real-world evidence (RWE) studies evaluating the incidence, prevalence, or recurrence of HD, as well as SLRs including a meta-analytic component reporting on the efficacy of systemic or topical pharmacological treatments for adults with HD, were included. Systematic searches were conducted in MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews.

    RESULTS: The SLR identified 44 eligible publications. Consistent data were limited on the epidemiology of HD or HD recurrence. Specifically, incidence and prevalence reported across geographies were impacted by differences in data collection. Reported risk factors for HD were sedentary behavior, constipation, male gender, and age. Twenty-three RWE studies and one meta-analysis reported HD recurrence rates ranging from 0 to 56.5% following surgery or phlebotonics, with most (n = 19) reporting rates of 20% or less. In addition to time since treatment, risk factors for recurring disease were similar to those for HD in general. With respect to treatment, micronized purified flavonoid fractions significantly improved the main symptoms of HD compared to other pharmacological treatments.

    CONCLUSION: The SLRs did not identify any RWE studies reporting recurrence in patients receiving systemic or topical treatments, highlighting the need for future research in this area. Further, more studies are needed to understand the optimum duration of medical treatment to prevent recurrence.

  10. Flavonoid diversity and roles in the lipopolysaccharide-mediated inflammatory response of monocytes and macrophages
    Rullah K, Shamsudin NF, Koeberle A, Tham CL, Fasihi Mohd Aluwi MF, Leong SW, et al.
    Future Med Chem, 2024 Jan;16(1):75-99.
    PMID: 38205612 DOI: 10.4155/fmc-2023-0174
    Targeting lipopolysaccharide (LPS)/toll-like receptor 4 signaling in mononuclear phagocytes has been explored for the treatment of inflammation and inflammation-related disorders. However, only a few key targets have been translated into clinical applications. Flavonoids, a class of ubiquitous plant secondary metabolites, possess a privileged scaffold which serves as a valuable template for designing pharmacologically active compounds directed against diseases with inflammatory components. This perspective provides a general overview of the diversity of flavonoids and their multifaceted mechanisms that interfere with LPS-induced signaling in monocytes and macrophages. Focus is placed on flavonoids targeting MD-2, IκB kinases, c-Jun N-terminal kinases, extracellular signal-regulated kinase, p38 MAPK and PI3K/Akt or modulating LPS-related gene expression.
  11. Fulltext Human Invasive Muscular Sarcocystosis Induces Th2 Cytokine Polarization and Biphasic Cytokine Changes, Based on an Investigation among Travelers Returning from Tioman Island, Malaysia
    Tappe D, Slesak G, Pérez-Girón JV, Schäfer J, Langeheinecke A, Just-Nübling G, et al.
    Clin Vaccine Immunol, 2015 Jun;22(6):674-7.
    PMID: 25903356 DOI: 10.1128/CVI.00042-15
    Sarcocystis nesbitti is a parasite responsible for a biphasic eosinophilic febrile myositis syndrome in two recent outbreaks in Malaysia. We demonstrate Th2 cytokine polarization in infected travelers, an overall cytokine production decrease in the early phase of the disease suggestive of initial immunosuppression, and elevated levels of proinflammatory and chemotactic cytokines in the later myositic phase.
  12. Fulltext Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray
    Chen YH, Lee HJ, Lee MT, Wu YT, Lee YH, Hwang LL, et al.
    Proc Natl Acad Sci U S A, 2018 11 06;115(45):E10720-E10729.
    PMID: 30348772 DOI: 10.1073/pnas.1807991115
    Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG. Such responses were not seen in mice with PC6 needle insertion only or electrical stimulation of the lateral deltoid, a nonmedian nerve-innervated location. Directly stimulating the surgically exposed median nerve also increased vlPAG orexin A levels. MNS-PC6-induced antinociception (MNS-PC6-IA) was prevented by proximal block of the median nerve with lidocaine as well as by systemic or intravlPAG injection of an antagonist of OX1Rs or cannabinoid 1 receptors (CB1Rs) but not by opioid receptor antagonists. Systemic blockade of OX1Rs or CB1Rs also restored vlPAG GABA levels after MNS-PC6. A cannabinoid (2-AG)-dependent mechanism was also implicated by the observations that MNS-PC6-IA was prevented by intravlPAG inhibition of 2-AG synthesis and was attenuated in Cnr1-/- mice. These findings suggest that PC6-targeting low-frequency MNS activates hypothalamic orexin neurons, releasing orexins to induce analgesia through a CB1R-dependent cascade mediated by OX1R-initiated 2-AG retrograde disinhibition in the vlPAG. The opioid-independent characteristic of MNS-PC6-induced analgesia may provide a strategy for pain management in opioid-tolerant patients.
  13. Fulltext Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania
    Reich D, Patterson N, Kircher M, Delfin F, Nandineni MR, Pugach I, et al.
    Am J Hum Genet, 2011 Oct 07;89(4):516-28.
    PMID: 21944045 DOI: 10.1016/j.ajhg.2011.09.005
    It has recently been shown that ancestors of New Guineans and Bougainville Islanders have inherited a proportion of their ancestry from Denisovans, an archaic hominin group from Siberia. However, only a sparse sampling of populations from Southeast Asia and Oceania were analyzed. Here, we quantify Denisova admixture in 33 additional populations from Asia and Oceania. Aboriginal Australians, Near Oceanians, Polynesians, Fijians, east Indonesians, and Mamanwa (a "Negrito" group from the Philippines) have all inherited genetic material from Denisovans, but mainland East Asians, western Indonesians, Jehai (a Negrito group from Malaysia), and Onge (a Negrito group from the Andaman Islands) have not. These results indicate that Denisova gene flow occurred into the common ancestors of New Guineans, Australians, and Mamanwa but not into the ancestors of the Jehai and Onge and suggest that relatives of present-day East Asians were not in Southeast Asia when the Denisova gene flow occurred. Our finding that descendants of the earliest inhabitants of Southeast Asia do not all harbor Denisova admixture is inconsistent with a history in which the Denisova interbreeding occurred in mainland Asia and then spread over Southeast Asia, leading to all its earliest modern human inhabitants. Instead, the data can be most parsimoniously explained if the Denisova gene flow occurred in Southeast Asia itself. Thus, archaic Denisovans must have lived over an extraordinarily broad geographic and ecological range, from Siberia to tropical Asia.
  14. Antithrombotic treatment for stroke prevention in atrial fibrillation: The Asian agenda
    Chen CH, Chen MC, Gibbs H, Kwon SU, Lo S, On YK, et al.
    Int J Cardiol, 2015 Jul 15;191:244-53.
    PMID: 25978611 DOI: 10.1016/j.ijcard.2015.03.369
    Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs a considerable burden of stroke and associated healthcare costs. Asians have AF risk factors similar to Caucasians and a similarly increased risk of AF-related stroke; however, with a vast and rapidly ageing population, Asia bears a disproportionately large disease burden. Urgent action is warranted to avert this potential health crisis. Antithrombotic therapy with oral anticoagulants is the most effective means of preventing stroke in AF and is a particular priority in Asia given the increasing disease burden. However, AF in Asia remains undertreated. Conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, in particular overuse of antiplatelet agents and underuse of anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor Xa inhibitors are non-inferior in preventing stroke and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. These agents may therefore provide an appropriate alternative to warfarin in Asian patients. There is considerable scope to improve stroke prevention in AF in Asia. Key priorities include: early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K antagonists for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among both physicians and patients.
  15. Fulltext Sequencing of Historical Isolates, K-mer Mining and High Serological Cross-Reactivity with Ross River Virus Argue against the Presence of Getah Virus in Australia
    Rawle DJ, Nguyen W, Dumenil T, Parry R, Warrilow D, Tang B, et al.
    Pathogens, 2020 Oct 16;9(10).
    PMID: 33081269 DOI: 10.3390/pathogens9100848
    Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original isolates (N544 and N554), illustrated that these viruses were virtually identical to the 1955 GETVMM2021 isolate from Malaysia. K-mer mining of the >40,000 terabases of sequence data in the Sequence Read Archive followed by BLASTn confirmation identified multiple GETV sequences in biosamples from Asia (often as contaminants), but not in biosamples from Australia. In contrast, sequence reads aligning to the Australian Ross River virus (RRV) were readily identified in Australian biosamples. To explore the serological relationship between GETV and other alphaviruses, an adult wild-type mouse model of GETV was established. High levels of cross-reactivity and cross-protection were evident for convalescent sera from mice infected with GETV or RRV, highlighting the difficulties associated with the interpretation of early serosurveys reporting GETV antibodies in Australian cattle and pigs. The evidence that GETV circulates in Australia is thus not compelling.
  16. Fulltext Polymer-free sirolimus-eluting stents in a large-scale all-comers population
    Krackhardt F, Kočka V, Waliszewski MW, Utech A, Lustermann M, Hudec M, et al.
    Open Heart, 2017 06 06;4(2):e000592.
    PMID: 28761678 DOI: 10.1136/openhrt-2017-000592
    OBJECTIVE: The objective of this study was to assess the safety and efficacy of a polymer-free sirolimus coated, ultrathin strut drug-eluting stent (PF-SES) in an unselected patient population with a focus on acute coronary syndrome (ACS). Furthermore, stable coronary artery disease (CAD) with short (≤6 months) versus long (>6 months) dual antiplatelet therapy (DAPT) were also studied.

    METHODS: Patients who received PF-SES were investigated in an unselected large-scale international, single-armed, multicenter, 'all comers' observational study. The primary endpoint was the 9-month target lesion revascularisation (TLR) rate, whereas secondary endpoints included the 9-month major adverse cardiac events (MACE) and procedural success rates. A priori defined subgroups such as patients with ACS, diabetes, lesion subsets and procedural characteristics relative to DAPT were investigated.

    RESULTS: A total of 2877 patients of whom 1084 had ACS were treated with PF-SES (1.31±0.75 stents per patient). At 9 months, the accumulated overall TLR rate was 2.3% (58/2513). There was no significant difference between ACS and stable CAD (2.6% vs 2.1%, p=0.389). However, the overall MACE rate was 4.3% (108/2513) with a higher rate in patients with ACS when compared with the stable CAD subgroup (6.1%, 58/947 vs 3.2%, 50/1566, p<0.001).

    CONCLUSIONS: PF-SES angioplasty is safe and effective in the daily clinical routine with low rates of TLR and MACE in an unselected patient population. Our data are in agreement with prior clinical findings that extended DAPT duration beyond 6 months do not improve clinical outcomes in patients with stable CAD (ClinicalTrials.gov Identifier NCT02629575).

    TRIAL REGISTRATION NUMBER: NCT02629575.

  17. Meta-Analysis of Gender Disparities in In-hospital Care and Outcomes in Patients with ST-Segment Elevation Myocardial Infarction
    Shah T, Haimi I, Yang Y, Gaston S, Taoutel R, Mehta S, et al.
    Am J Cardiol, 2021 05 15;147:23-32.
    PMID: 33640366 DOI: 10.1016/j.amjcard.2021.02.015
    Gender disparities in ST-segment elevation myocardial infarction (STEMI) outcomes continue to be reported worldwide; however, the magnitude of this gap remains unknown. To evaluate gender-based discrepancies in clinical outcomes and identify the primary driving factors a global meta-analysis was performed. Studies were selected if they included all comers with STEMI, reported gender specific patient characteristics, treatments, and outcomes, according to the registered PROSPERO protocol: CRD42020161469. A total of 56 studies (705,098 patients, 31% females) were included. Females were older, had more comorbidities and received less antiplatelet therapy and primary percutaneous coronary intervention (PCI). Females experienced significantly longer delays to first medical contact (mean difference 42.5 min) and door-to-balloon time (mean difference 4.9 min). In-hospital, females had increased rates of mortality (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.84 to 1.99, p <0.00001), repeat myocardial infarction (MI) (OR 1.25, 95% CI 1.00 to 1.56, p=0.05), stroke (OR 1.67, 95% CI 1.27 to 2.20, p <0.001), and major bleeding (OR 1.82, 95% CI 1.56 to 2.12, p <0.00001) compared with males. Older age at presentation was the primary driver of excess mortality in females, although other factors including lower rates of primary PCI and aspirin usage, and longer door-to-balloon times contributed. In contrast, excess rates of repeat MI and stroke in females appeared to be driven, at least in part, by lower use of primary PCI and P2Y12 inhibitors, respectively. In conclusion, despite improvements in STEMI care, women continue to have in-hospital rates of mortality, repeat MI, stroke, and major bleeding up to 2-fold higher than men. Gender disparities in in-hospital outcomes can largely be explained by age differences at presentation but comorbidities, delays to care and suboptimal treatment experienced by women may contribute to the gender gap.
  18. Prospective study of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients who are not suitable for stem cell transplant or multi-agent chemotherapy
    Walewski J, Hellmann A, Siritanaratkul N, Ozsan GH, Ozcan M, Chuncharunee S, et al.
    Br J Haematol, 2018 11;183(3):400-410.
    PMID: 30168134 DOI: 10.1111/bjh.15539
    Some patients with relapsed/refractory Hodgkin lymphoma (HL) are not considered suitable for stem cell transplant (SCT) and have a poor prognosis. This phase IV study (NCT01990534) evaluated brentuximab vedotin (1·8 mg/kg intravenously once every 3 weeks) in 60 patients (aged ≥18 years) with CD30-positive relapsed/refractory HL, a history of ≥1 prior systemic chemotherapy regimen, who were considered unsuitable for SCT/multi-agent chemotherapy. Primary endpoint was overall response rate (ORR) per independent review facility (IRF). Secondary endpoints included duration of response (DOR), progression-free survival (PFS) per IRF, overall survival (OS), proportion proceeding to SCT and safety. The ORR was 50%, with 12% CR; 47% proceeded to SCT. Median DOR was 4·6 months and median duration of CR was 6·1 months. After a median follow-up of 6·9 and 16·6 months, median PFS and OS were 4·8 months (95% confidence interval, 3·0-5·3) and not reached, respectively; estimated OS rate was 86% at 12 months. Most common adverse events (≥10%) were peripheral neuropathy (35%), pyrexia (18%), diarrhoea and neutropenia (each 10%). Brentuximab vedotin showed notable activity with a safety profile consistent with known toxicities, and may act as a bridge to SCT, enabling high-risk patients who achieve suboptimal response to frontline/salvage chemotherapy/radiotherapy to receive potentially curative SCT.
  19. A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease
    Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al.
    COPD, 2017 Oct;14(5):476-483.
    PMID: 28753067 DOI: 10.1080/15412555.2017.1335697
    Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.
  20. Fulltext Real-world effectiveness and safety of ranibizumab for the treatment of myopic choroidal neovascularization: Results from the LUMINOUS study
    Hamilton RD, Clemens A, Minnella AM, Lai TYY, Dai H, Sakamoto T, et al.
    PLoS One, 2020;15(1):e0227557.
    PMID: 31961888 DOI: 10.1371/journal.pone.0227557
    PURPOSE: To assess the 1-year effectiveness, safety, and treatment patterns of ranibizumab in patients with myopic choroidal neovascularization (mCNV) enrolled in the LUMINOUS study.

    METHODS: This 5-year, prospective, multicenter, observational, study enrolled 30,138 patients across all approved ranibizumab indications from outpatient ophthalmology clinics. 297 consenting patients (≥18 years) with mCNV who were treatment-naïve or prior-treated with ranibizumab or other ocular treatments were enrolled, and treated with ranibizumab according to the local product label. The main outcomes are visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters or equivalent), adverse events during the study, and treatment exposure over 1 year. Results are presented by prior treatment status of the study eye and injection frequency.

    RESULTS: Of the 297 mCNV patients recruited in the study, 108 were treatment-naïve and 175 were prior ranibizumab-treated. At baseline, the mean age of patients was 57.6 years, and 59.0 years and 80.6% and 65.7% were female in the treatment-naïve and prior ranibizumab-treated groups, respectively. Most were Caucasian (treatment-naïve, 88.9%; prior ranibizumab-treated, 86.9%). The mean (±standard deviation [SD]) VA letter changes to 1 year were +9.7 (±17.99) from 49.5 (±20.51) and +1.5 (±13.15) from 58.5 (±19.79) and these were achieved with a mean (SD) of 3.0 (±1.58) and 2.6 (±2.33) injections in the treatment-naïve and prior ranibizumab-treated groups, respectively. Presented by injection frequencies 1-2, 3-4 and ≥5 injections in Year 1, the mean (SD) VA changes were +15.0 (±14.70), +7.7 (±19.91) and -0.7 (±16.05) in treatment-naïve patients and +1.5 (±14.57), +3.1 (±11.53) and -3.6 (±11.97) in prior ranibizumab-treated patients, respectively. The safety profile was comparable with previous ranibizumab studies.

    CONCLUSIONS: Ranibizumab treatment for mCNV showed robust VA gains in treatment-naïve patients and VA maintenance in prior ranibizumab-treated patients in a clinical practice setting, consisting mainly of Caucasians. No new safety signals were observed during the study.

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