Date
All
Search in:AllTitleAbstractAuthor name
Publications
(31M+)
Patents
(667K+)
Grants
(2M+)
Pathways
(531)
Clinical trials
(327K+)
Publication
Journal: Parasite immunology
May/17/2020
Abstract
Visceral leishmaniasis (VL) is caused by a protozoan parasite Leishmania donovani mainly influencing the population of tropical and subtropical regions across the globe. The arsenal of drugs available is limited, and prolonged use of such drugs makes parasite to become resistant. Therefore, it is very imperative to develop a safe, cost-effective and inexpensive vaccine against VL. Although in recent years many strategies have been pursued by researchers, but so far only some of the vaccine candidates reached for clinical trial and more than half of them are still in pipeline. There is now a broad consent among Leishmania researchers that the perseverance of parasite is very essential for eliciting a protective immune response and may perhaps be attained by live attenuated parasite vaccination. For making a live attenuated parasite it is very essential to ensure that the parasite is deficient of virulence and should further study genetically modified parasites to perceive the mechanism of pathogenesis. So it is believed that in the near future, a complete understanding of the Leishmania genome will explore clear strategies to discover a novel vaccine. This review describes the need for a genetically modified live attenuated vaccine against VL, and obstacles associated with its development.
Publication
Journal: Hepatology (Baltimore, Md.)
May/17/2020
Abstract
We would like to thank Selck et al. for their letter. The issue they raise has both methodological and scientific interest. We clearly acknowledge in our discussion the limitations of our approach to estimate the causal impact of cold weather on alcoholic cirrhosis at a population level. In addition, as highlighted in the accompanying editorial, these associations at a population level might not hold at an individual level, and the causes of differences in alcohol intake between populations and individuals might not be the same.
Publication
Journal: Medical physics
May/17/2020
Abstract
Major advances in external beam radiation therapy in the last decade have provided technologies for planning and delivering highly conformal radiation dose distributions made available by refined beam targeting methods, including intensity-modulated radiation therapy using tomotherapy, volumetric modulated arc therapy and many other auspicious tools for 3D dose painting. The emergence of magnetic resonance imaging (MRI) systems integrated with linear accelerators (linacs), commonly known as an MR-linacs, have realized MR-image guided radiation therapy (MRgRT) systems.
Publication
Journal: Applied microbiology and biotechnology
May/17/2020
Abstract
Ulcerative colitis (UC), a kind of inflammatory bowel disease, is generally characterized by chronic, persistent, relapsing, and nonspecific ulceration of the bowel, which is widespread in the world. Although the pathogenesis of UC is multifactorial, growing evidence has demonstrated that gut microbiota and its metabolites are closely related to the development of UC. Lizhong decoction (LZD), a well-known classical Chinese herbal prescription, has been used to clinically treat UC for long time, but its mechanism is not clear. In this study, 16S rRNA gene sequencing combining with untargeted metabolomics profiling was used to investigate how LZD worked. Results indicated that LZD could shape the gut microbiota structure and modify metabolic profiles. The abundance of opportunistic pathogens such as Clostridium sensu stricto 1, Enterobacter, and Escherichia-Shigella correlated with intestinal inflammation markedly decreased, while the levels of beneficial bacteria including Blautia, Muribaculaceae_norank, Prevotellaceae UCG-001, and Ruminiclostridium 9 elevated in various degrees. Additionally, fecal metabolite profiles reflecting microbial activities showed that adenosine, lysoPC(18:0), glycocholic acid, and deoxycholic acid notably decreased, while cholic acid, α-linolenic acid, stearidonic acid, and L-tryptophan significantly increased after LZD treatment. Hence, based on the systematic analysis of 16S rRNA gene sequencing and metabolomics of gut flora, the results provided a novel insight that microbiota and its metabolites might be potential targets for revealing the mechanism of LZD on amelioration of UC.Key Points • The potential mechanism of LZD on the amelioration of UC was firstly investigated.• LZD could significantly shape the structure of gut microbiota.• LZD could notably modulate the fecal metabolic profiling of UC mice. Graphical abstract.
Publication
Journal: Applied microbiology and biotechnology
May/17/2020
Abstract
Due to a high unresponsiveness to chemotherapy, biofilm formation is an important medical problem that frequently occurs during infection with many bacterial pathogens. In this study, the marine sponge-derived natural compounds 4,6-dibromo-2-(2',4'-dibromophenoxy)phenol and 3,4,6-tribromo-2-(2',4'-dibromophenoxy)phenol were found to exhibit broad antibacterial activity against medically relevant gram-positive and gram-negative pathogens. The compounds were not only bactericidal against both replicating and stationary phase-persistent planktonic cells of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa; they also killed biofilm-incorporated cells of both species while not affecting biofilm structural integrity. Moreover, these compounds were active against carbapenemase-producing Enterobacter sp. This simultaneous activity of compounds against different growth forms of both gram-positive and gram-negative bacteria is rare. Genome sequencing of spontaneous resistant mutants and proteome analysis suggest that resistance is mediated by downregulation of the bacterial EIIBC phosphotransferase components scrA and mtlA in MRSA likely leading to a lower uptake of the molecules. Due to their only moderate cytotoxicity against human cell lines, phenoxyphenols provide an interesting new scaffold for development of antimicrobial agents with activity against planktonic cells, persisters and biofilm-incoporated cells of ESKAPE pathogens. KEY POINTS: • Brominated phenoxyphenols kill actively replicating and biofilm-incorporated bacteria. • Phosphotransferase systems mediate uptake of brominated phenoxyphenols. • Downregulation of phosphotransferase systems mediate resistance.
Publication
Journal: Cellular oncology (Dordrecht)
May/17/2020
Abstract
Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality in women worldwide. Despite various attempts to improve the diagnosis and therapy of ovarian cancer patients, the survival rate for these patients is still dismal, mainly because most of them are diagnosed at a late stage. Up to 90% of ovarian cancers arise from neoplastic transformation of ovarian surface epithelial cells, and are usually referred to as epithelial ovarian cancer (EOC). Unlike most human cancers, which are disseminated through blood-borne metastatic routes, EOC has traditionally been thought to be disseminated through direct migration of ovarian tumor cells to the peritoneal cavity and omentum via peritoneal fluid. It has recently been shown, however, that EOC can also be disseminated through blood-borne metastatic routes, challenging previous thoughts about ovarian cancer metastasis.Here, we review our current understanding of the most updated cellular and molecular mechanisms underlying EOC metastasis and discuss in more detail two main metastatic routes of EOC, i.e., transcoelomic metastasis and hematogenous metastasis. The emerging concept of blood-borne EOC metastasis has led to exploration of the significance of circulating tumor cells (CTCs) as novel and non-invasive prognostic markers in this daunting cancer. We also evaluate the role of tumor stroma, including cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs), endothelial cells, adipocytes, dendritic cells and extracellular matrix (ECM) components in EOC growth and metastasis. Lastly, we discuss therapeutic approaches for targeting EOC. Unraveling the mechanisms underlying EOC metastasis will open up avenues to the design of new therapeutic options. For instance, understanding the molecular mechanisms involved in the hematogenous metastasis of EOC, the biology of CTCs, and the detailed mechanisms through which EOC cells take advantage of stromal cells may help to find new opportunities for targeting EOC metastasis.
Publication
Journal: Stem cell reviews and reports
May/17/2020
Abstract
Aging impairs the regenerative potential of hematopoietic stem cells (HSC) and skews differentiation towards the myeloid lineage. The bone marrow (BM) microenvironment has recently been suggested to influence HSC aging, however the mechanisms whereby BM stromal cells mediate this effect is unknown. Here we show that aging-associated decreased expression of CXCR4 expression on BM mesenchymal stem cells (MSC) plays a crucial role in the development of the hematopoietic stem and progenitor cells (HSPC) aging phenotype. The BM MSC from old mice was sufficient to drive a premature aging phenotype of young HSPC when cultured together ex vivo. The impaired ability of old MSC to support HSPC function is associated with reduced expression of CXCR4 on BM MSC of old mice. Deletion of the CXCR4 gene in young MSC accelerates an aging phenotype in these cells characterized by increased production of reactive oxygen species (ROS), DNA damage, senescence, and reduced proliferation. Culture of HSPC from young mice with CXCR4 deficient MSC also from young mice led to a premature aging phenotype in the young HSPC, as evidenced by reduced hematopoietic regeneration and enhanced myeloid differentiation. Mechanistically, CXCR4 signaling prevents BM MSC dysfunction by suppressing oxidative stress, as treatment of old or CXCR4 deficient MSC with N-acetyl-L-cysteine (NAC), improved their niche supporting activity, and attenuated the HSPC aging phenotype. Our studies suggest that age-associated reduction in CXCR4 expression on BM MSC impairs hematopoietic niche activity with increased ROS production, driving an HSC aging phenotype. Thus, modulation of the SDF-1/CXCR4 axis in MSC may lead to novel interventions to alleviate the age-associated decline in immune/hematopoietic function.
Publication
Journal: Surgical and radiologic anatomy : SRA
May/17/2020
Abstract
The acromial and coracoid process morphology is of clinical relevance due to associations with functional limitations and shoulder pathology. Our objective was to describe the anatomical characteristics of the acromial and coracoid process using computed tomography (CT).Descriptive, observational, transversal and retrospective study. A total of 155 CT of patients without shoulder pathology, of both genders, and indistinct age were evaluated and grouped by age: Group 1 < 25 years; group 2 25-40 years; group 3 > 40 years. The following parameters were evaluated: Acromial type (AcT), vertical coracoid distance (VCD), acromial tilt (AT), acromial projection (AP), critical shoulder angle (CSA), type of the subcoracoid outlet (TSO), and the area of the subcoracoid outlet (ASO).

RESULTS
Statistically significant differences were found between men and women for VCD (14.44 ± 4.79 vs. 11.76 ± 4.00 mm; p < 0.001) and AP (3.66 ± 4.71 vs. 1.62 ± 4.99 mm; p < 0.05) as well as between age groups 1 and 3 for AT (35.08 ± 11.53 vs. 28.41 ± 6.60; p < 0.05) and ASO (398.99 ± 153.91 vs. 255.56 ± 124.58 mm2; p < 0.001). An unexpected high ASO variation was identified with 11% of S-shaped acromion and 1.3% clock-shaped TSO.

The age group between 25-40 years had the most uniform distribution of data. There is a high morphological variability present in an asymptomatic population, which should be considered in the clinical assessment such as shoulder impingement syndrome.
Publication
Journal: Surgical and radiologic anatomy : SRA
May/17/2020
Abstract
To determine the microsurgical features of the spinal cord and ventral and dorsal rootlets in fetal period.Twelve formalin-fixed fetuses (six females and six males) with a mean gestational age of 27.0 ± 2.04 weeks (range between 25 and 32 weeks) were dissected to evaluate morphological properties of the spinal cord and rootlets.Length and width of each spinal cord segment, number of dorsal and ventral rootlets, length of dorsal root entry and ventral root exit zones of each spinal nerve, spinal cord termination level, and the whole spinal cord length were determined in all fetuses. Contrary to previous reports, the number of ventral rootlets was always more than that of dorsal rootlets in all segments. No statistically significant gender difference was found for all parameters. Rootlet number and segment width in cervical region were larger than those of thoracic, while the lengths of dorsal root entry and ventral root exit zones in thoracic region were longer than those of cervical. In lumbar region, dorsal and ventral rootlet numbers were increasing again, while lengths of dorsal root entry and ventral root exit zones were decreasing. Number of dorsal and ventral rootlets of C5 and C6 segments was statistically higher than other cervical segments. The mean spinal cord length was found as 105.55 ± 11.30 mm and there was a positive significant relationship with gestational age. Conus medullaris level was detected between L1 and L3 segments.Detailed microsurgical data about the fetal spinal cord and the dorsal and ventral rootlets presented in this study provide significant information which may be essential during surgical interventions in early postnatal period and childhood targeting the spinal cord and spinal nerve roots.
Publication
Journal: Theory in biosciences = Theorie in den Biowissenschaften
May/17/2020
Abstract
Embryonic development, which inspired the first theories of biological form, was eventually excluded from the conceptual framework of the Modern Synthesis as irrelevant. A major question during the last decades has centred on understanding whether new advances in developmental biology are compatible with the standard view or whether they compel a new theory. Here, I argue that the answer to this question depends on which concept of morphogenesis is held. Morphogenesis can be conceived as (1) a chemically driven or (2) a mechanically driven process. According to the first option, genetic regulatory networks drive morphogenesis. According to the second, morphogenesis results from an invariant tendency of embryonic tissues to restore changes in mechanical stress. While chemically driven morphogenesis allows an extension of the standard view, mechanically driven morphogenesis would deeply transform it. Which of these hypotheses has wider explanatory power is unknown. At present, the problem of biological form remains unsolved.
Publication
Journal: Journal of medical toxicology : official journal of the American College of Medical Toxicology
May/17/2020
Publication
Journal: Journal of experimental orthopaedics
May/17/2020
Publication
Journal: Clinical rheumatology
May/17/2020
Abstract
To assess the effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath of dactylitis in psoriatic arthritis (PsA) patients as compared with systemic treatment (ST).Forty-six PsA patients with a total of 73 dactylitic fingers were assessed in an observational, multicentre, prospective study by the Leeds Dactylitis Index basic (LDI-b) score and evaluated for local pain (visual analogue scale-VAS pain) and functional impairment (VAS-FI). Steroid injection was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Both the groups continued baseline csDMARDs and/or corticosteroids therapy. The clinical outcomes were measured at baseline, 1 month (T1) and 3 months (T3).The reduction of VAS-pain, VAS-FI and LDI-b values was statistically significant higher in the LT group (24 patients, 38 dactylitic fingers) as compared with the ST group (22 patients, 35 dactylitic fingers), both at T1 (p < 0.001, p < 0.001 and p = 0.008, respectively) and at T3 (p < 0.001, p < 0.001 and p < 0.001, respectively). A clinically meaningful treatment response (defined as a contemporary reduction of at least 5 points in VAS-pain and VAS-FI or as values of VAS-pain and VAS-FI were both ≤ 2) was observed at T1 in 33 (87%) digits in LT group and in 6 (17%) digits in ST group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference (94% vs 31%, p < 0.001).For the first time, we show the effectiveness of steroid injection into the digital flexor tendon sheath in improving clinical aspects of hand psoriatic dactylitis.Key Points• Therapy with steroid injection (local treatment, LT), into the digital flexor tendon sheath for the treatment of active dactylitis in psoriatic arthritis patients, is more effective when compared with systemic treatment (ST) alone.• The reduction of VAS-pain, VAS-functional impairment (VAS-FI) and Leeds Dactylitis Index basic values was statistically significant higher in the LT group as compared with the ST group, both at T1and at T3.• A clinically meaningful response was observed at T1 in 87% of digits of patients treated with steroid injection and in 17% of digits of the systemic treatment group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference.• For the first time, findings from this study show that the use of steroid injections into the digital flexor tendon sheath for psoriatic dactylitis could be an effective and safe first-line therapy for psoriatic dactylitis.
Publication
Journal: Clinical drug investigation
May/17/2020
Abstract
Over the past 5 years, adjuvant treatment options for surgically resected stage III melanoma have expanded with the introduction of several novel immune checkpoint inhibitors and targeted therapies. Pembrolizumab, a programmed cell death protein 1 inhibitor, received US Food and Drug Administration approval in 2019 for resected high-risk stage III melanoma based on significantly longer recurrence-free survival versus placebo. This study evaluated the cost-effectiveness of pembrolizumab versus other adjuvant treatment strategies for resected high-risk stage III melanoma from a US health system perspective.A Markov cohort-level model with four states (recurrence-free, locoregional recurrence, distant metastases, death) estimated costs and quality-adjusted life-years (QALYs) for pembrolizumab versus routine observation and other adjuvant comparators: ipilimumab in the overall population; and dabrafenib + trametinib in the BRAF-mutation positive (BRAF+) subgroup. Transition probabilities starting from recurrence-free were estimated through parametric multi-state modeling based on phase 3 KEYNOTE-054 (NCT02362594) trial data for pembrolizumab and observation, and network meta-analyses for other comparators. Post-recurrence transitions were modeled based on electronic medical records data and trials in advanced/metastatic melanoma. Utilities were derived using quality-of-life data from KEYNOTE-054 and literature. Costs of treatment, adverse events, disease management, and terminal care were included.Over a lifetime, pembrolizumab, ipilimumab, and observation were associated with QALYs of 9.24, 7.09, and 5.95 and total costs of $511,290, $992,721, and $461,422, respectively (2019 US dollars). Pembrolizumab was thus dominant (less costly, more effective) versus ipilimumab, with an incremental cost-effectiveness ratio of $15,155/QALY versus observation. In the BRAF+ subgroup, pembrolizumab dominated dabrafenib + trametinib and observation, decreasing costs by $62,776 and $11,250 and increasing QALYs by 0.93 and 3.10 versus these comparators, respectively. Results were robust in deterministic and probabilistic sensitivity analyses.As adjuvant treatment for resected stage III melanoma, pembrolizumab was found to be dominant and therefore cost-effective compared with the active comparators ipilimumab and dabrafenib + trametinib. Pembrolizumab increased costs relative to observation in the overall population, with sufficient incremental benefit to be considered cost-effective based on typical willingness-to-pay thresholds.
Publication
Journal: Breast cancer research and treatment
May/17/2020
Abstract
The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited.The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument.Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6-33.7], the median PFS was 6.2 months (95% CI 5.2-7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients < and ≥ 70 years of age. The patients' baseline FACT-B total score remained unchanged. The serious and non-serious adverse event incidence rates were 13% and 48%, respectively.This prospective study provides further evidence on quality of life, efficacy, and safety of nab-paclitaxel in patients with MBC and sheds more light in special subpopulations such as the elderly and those treated beyond the second line.
Publication
Journal: Clinical rheumatology
May/17/2020
Abstract
Immune thrombocytopenia (ITP) is a common complication of connective tissue diseases (CTD). However, refractory and recurrent cases are frequent, who often need intensive immunotherapy. In the real world to compare the efficacy and safety of two common options, rituximab (RTX) and cyclosporine (CsA), in patients with refractory CTD-ITP, we conducted this retrospective study. Inpatients diagnosed with CTD-ITP who experienced treatment failure with initial prednisone or other immunosuppressants and who subsequently received either RTX or CsA between 2013 and 2018 were identified. All the patients were followed up for at least 6 months. Remission was defined as sustained platelet count ≥ 50 × 10^9/L, where ≥ 100 × 10^9/L was considered complete remission and 50-100 × 10^9/L was considered partial remission. Propensity score weighting analysis was performed to balance the confounders as indication. A total of 83 patients with CTD-ITP were identified, of whom 43 had systemic lupus erythematosus, 24 had undifferentiated CTD, and 16 had primary Sjogren syndrome. The RTX group (n = 53) had a much higher remission rate than the CsA group (n = 30) after 3 months and throughout the following 3 months (3 m, 86.8% vs 63.6%, p = 0.025; 6 m, 81.8% vs 53.5%, p = 0.011). Binary logistic regression analysis confirmed that treatment with RTX predicted better outcome (OR 4.09, 1.42 ~ 11.79), while age > 50 (OR 0.31, 0.11 ~ 0.93) was a risk factor. Furthermore, we reinforced the conclusions by propensity score weighting analysis (RTX OR 4.89, 1.64 ~ 14.58; age > 50 OR 0.31, 0.12 ~ 0.83). In our real-world retrospective study, for patients with refractory CTD-ITP, RTX was superior to CsA in terms of the durable remission rate.Key Points:• Refractory cases are common in patients with immune thrombocytopenia secondary to connective tissue diseases (CTD-ITP), requiring intensive immunotherapy.• Randomized controlled trials comparing rituximab and a traditional immunosuppressive agents (IS), such as cyclosporin, are lacking in these patients.• Our real-word retrospective study indicated that rituximab was superior to cyclosporin in patients with refractory CTD-ITP.
Publication
Journal: Breast cancer research and treatment
May/17/2020
Abstract
Accurate prediction of pathologic complete response (pCR) in breast cancer using magnetic resonance imaging (MRI) and ultrasound (US)-guided biopsy may aid in selecting patients who forego surgery for breast cancer. We evaluated the accuracy of US-guided biopsy aided by MRI in predicting pCR in the breast after neoadjuvant chemotherapy (NAC).After completion of NAC, 40 patients with near pCR (either tumor size ≤ 0.5 cm or lesion-to-background signal enhancement ratio (L-to-B SER) ≤ 1.6 on MRI) and no diffused residual microcalcifications were prospectively enrolled at a single institution. US-guided multiple core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) of the tumor bed, followed by standard surgical excision, was performed. Matched biopsy and surgical specimens were compared to assess pCR. The negative predictive value (NPV), accuracy, and false-negative rate (FNR) were analyzed.pCR was confirmed in 27 (67.5%) surgical specimens. Preoperative biopsy had an NPV, accuracy, and FNR of 87.1%, 90.0%, and 30.8%, respectively. NPV for hormone receptor-negative and hormone receptor-positive tumors were 83.3% and 100%, respectively. Obtaining at least 5 biopsy cores based on tumor size ≤ 0.5 cm and an L-to-B SER of ≤ 1.6 on MRI (27 patients) resulted in 100% NPV and accuracy. No differences in accuracy were noted between CNB and VAB (90% vs. 90%).Investigation using stringent MRI criteria and ultrasound-guided biopsy could accurately predict patients with pCR after NAC. A larger prospective clinical trial evaluating the clinical safety of breast surgery omission after NAC in selected patients will be conducted based on these findings.
Publication
Journal: Clinical rheumatology
May/17/2020
Abstract
Periarticular osteophyte formation is observed during the repair of damaged joints in rheumatoid arthritis (RA); however, little is known about its clinical and functional roles. This study aimed to determine the influence of periarticular osteophyte formation on the incidence of total knee arthroplasty (TKA) (a surrogate for long-term outcomes of joint destruction) in patients with RA.This retrospective longitudinal study included a total of 130 symptomatic (tender and/or swollen) knee joints in 80 patients starting biologics. Cumulative incidences of TKA were compared according to the presence or absence of osteophyte on plain anteroposterior radiograph (osteophyte (±)) and the extent of advanced joint damage as defined by Larsen's grading system (0-II vs. III-V).Kaplan-Meier estimates showed a significantly lower cumulative incidence of TKA for the osteophyte (+) group (n = 33) compared with the osteophyte (-) group (n = 31) in the Larsen grades III-V group (38 vs. 74% at 10 years, P = 0.010), whereas no significant difference was observed between the osteophyte (+) (n = 11) and osteophyte (-) (n = 55) groups in the Larsen grades 0-II group (9 vs. 10% at 10 years). Multivariate Cox proportional hazards analysis revealed that older age (hazard ratio (HR), 1.04 per 1 year; 95% confidence interval (CI), 1.01-1.08) and osteophyte formation (HR, 0.39; 95% CI, 0.19-0.79) independently predicted TKA in the Larsen grades III-V group, whereas none of the assessed variables predicted TKA in the Larsen grades 0-II group.Osteophyte formation reduces the incidence of TKA in patients with RA who have advanced joint damage.Key Points• Older age and Larsen grade were independent predictors of total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients.• Periarticular osteophyte formation reduced the incidence of TKA in RA patients with Larsen grades III-V.
Publication
Journal: Clinical rheumatology
May/17/2020
Abstract
A 5-year-old female child, with known systemic juvenile idiopathic arthritis diagnosed at 18 months of age (on low dose Prednisolone + Methotrexate + Leflunomide + Tocilizumab), presented with fever for 1 day, vomiting, drowsiness followed by seizures. On admission to PICU, she was drowsy, tachycardic, tachypneic, with rashes, and hepatosplenomegaly. Lab findings showed thrombocytopenia, leucopenia, low ESR, normal CRP, elevated liver enzymes, high ferritin, LDH, and triglycerides suggestive of macrophage activation syndrome (MAS). Chest X-ray showed left basal pneumonia and DNA PCR of throat swab revealed adenovirus. She was diagnosed as adenovirus-triggered MAS and was initiated on pulse methylprednisolone (6 mg/kg). Because of suboptimal response after 2 doses, manifested by increasing drowsiness, further fall in platelets and rising ferritin, methylprednisolone dosage was increased to 30 mg/kg/day with the addition of oral cyclosporine (4 mg/kg/day). In view of worsening of the chest X-ray and increasing oxygen requirement, Cidofovir infusion (1 mg/kg thrice weekly) was also started simultaneously considering increased activity of the adenoviral infection concurrent to immunosuppression. Within 48 h, the child showed signs of recovery with improved consciousness, lower oxygen requirements, and improving lab parameters. She was discharged after 3 weeks of IV Cidofovir, on oral prednisolone and cyclosporine. To the best of our knowledge, this is the first reported use of Cidofovir in adenovirus-induced MAS.
Publication
Journal: Clinical rheumatology
May/17/2020
Publication
Journal: Clinical rheumatology
May/17/2020
Publication
Journal: Annals of hematology
May/17/2020
Abstract
Follicular lymphoma (FL) is an indolent non-Hodgkin's lymphoma with heterogeneous outcomes. Progression or relapse of FL within 2 years (so-called POD24) after diagnosis is associated with a poor outcome for patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) in clinical trials. POD24 needs further validation before it can be used as a relevant endpoint to assess treatment efficacy. In the present retrospective monocentric study, we investigated the predictive value of POD24 in a cohort of grade 1, 2, or 3a FL patients treated in our institution (Nantes Medical University, France) and registered in our local database. We investigated the nature of treatment lines, patients' outcomes, and the prognostic value of POD24. Between 2007 and 2016, 317 patients were included. After first-line therapy, 60 patients relapsed within 2 years (POD24-pos cohort), and 254 patients did not relapse within 2 years (PO24-neg cohort). Thirty-three patients died, and 34 patients had an aggressive transformation. The median follow-up is 59.9 months (1.6-395.5). The median PFS is 59.9 months. Overall survival (OS) at 1 year, 3 years, and 5 years is 98.4% [97.0-99.8], 95.1% [92.6-97.6], and 92.5% [89.3-95.9], respectively. The 5-year OS was statistically lower for POD24-pos patients (82% [71.9-93.5]) than for POD24-neg patients (93.3% [88.98-97.8]) (p = 10-5). In multivariate analyses, transformation was predictive of OS, and PS (≥ 1) was predictive of POD24. POD24 is predictive of a worse OS and may be recommended as a relevant endpoint in clinical trials and in real life in particular for patients with advanced disease.
Publication
Journal: Cancer chemotherapy and pharmacology
May/17/2020
Abstract
Glioblastoma is the most devastating primary brain tumor and effective therapies are not available. Treatment is based on surgery followed by radio and chemotherapy with temozolomide (TMZ), but TMZ increases patient survival only by 2 months. CD73, an enzyme responsible for adenosine production, emerges as a target for glioblastoma treatment. Indeed, adenosine causes tumor-promoting actions and CD73 inhibition increases sensitivity to TMZ in vitro. Here, a cationic nanoemulsion to nasal delivery of siRNA CD73 (NE-siRNA CD73) aiming glioblastoma treatment was employed alone or in combination with TMZ. In vitro, two glioblastoma cell lines (C6 and U138MG) with a chemo-resistant profile were used. Treatment alone with NE-siRNA CD73 reduced C6 and U138MG glioma cell viability by 70% and 25%, respectively. On the other hand, when NE-siRNA + TMZ combined treatment was employed, a reduction of 85% and 33% of cell viability was observed. Notably, treatment with NE-siRNA CD73 of glioma-bearing Wistar rats reduced tumor size by 80%, 60% more than the standard chemotherapy with TMZ, but no synergistic or additive effect was observed in vivo. Additionally, NE-siRNA CD73, TMZ or combined therapy decreased adenosine levels in liquor confirming the importance of this nucleoside on in vivo GB growth. Finally, no hemolytic potential was observed. These results suggest that nasal administration of NE-siRNA CD73 exhibits higher antiglioma effect when compared to TMZ. However, no synergistic or additive in vivo was promoted by the therapeutic regimen employed in this study.
Publication
Journal: Journal of neuropathology and experimental neurology
May/17/2020
Abstract
Choroid plexus (CP) may aid brain development and repair by secreting growth factors and neurotrophins for CSF streaming to ventricular and subventricular zones. Disrupted ventricular/subventricular zone progenitors and stem cells lead to CNS maldevelopment. Exploring models, we organ cultured the CP and transplanted fresh CP into a lateral ventricle of postnatal hydrocephalic (hyHTx) and nonhydrocephalic (nHTx) rats. After 60 days in vitro, the cultured choroid ependyma formed spherical rings with beating cilia. Cultured CP expressed endocytotic caveolin 1 and apical aquaporin 1 and absorbed horseradish peroxidase from medium. Transthyretin secretory protein was secreted by organ-cultured CP into medium throughout 60 days in vitro. Fresh CP, surviving at 1 week after lateral ventricle implantation of nHTx or hyHTx did not block CSF flow. Avascular 1-week transplants in vivo expressed caveolin 1, aquaporin 1, and transthyretin, indicating that grafted CP may secrete trophic proteins but not CSF. Our findings encourage further exploration on CP organ culture and grafting for translational strategies. Because transplanted CP, though not producing CSF, may secrete beneficial molecules for developing brain injured by hydrocephalus, we propose that upon CP removal in hydrocephalus surgery, the fractionated tissue could be transplanted back (ventricular autograft).
load more...