Tag: nevin manimala

Cell Mol Biol (Noisy-le-grand). 2023 Jul 31;69(7):71-79. doi: 10.14715/cmb/2023.69.7.12.

ABSTRACT

The roles of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3C (A3C) in various human malignancies are not consistent. A3C expression is correlated with early-stage breast cancer and is presented as a good prognostic factor; however, it induces fewer therapeutic effects of cytotoxic drugs in low-grade gliomas. To explore the impact of A3C on gliomas, a statistical analysis of several public databases was conducted. The results showed that enhanced A3C expression was associated with advanced tumor grades and poor expression of prognostic factors. Similarly, our in vitro study revealed that glioblastoma (GBM) cell lines had higher A3C mRNA and protein expression than that of normal brain tissue cDNA and lysates. We first performed an immunohistochemical stain (IHC) to prove that gliomas with high A3C expression presented the wild type-Isocitrate dehydrogenase 1 (IDH1), and they had an unfavorable prognosis in human glioma tissues. In addition, the oncological factors associated with A3C expression suggested that DNA repair pathways are important mechanisms for inducing tumorigenesis and chemoresistance in gliomas. Moreover, a significant correlation was observed between A3C expression and proteolipid protein 2 (PLP2). Reactive oxygen species (ROS) -activated PLP2 prevents DNA damage-induced cell apoptosis. Compared to high immunostaining scores for A3C and/or PLP2 expression, combined low immunostaining scores for A3C and PLP2 correlated with improved survival in gliomas; however, the detailed mechanism is to be elucidated. In conclusion, our results not only confirmed A3C played an important role in glioma development, but the A3C IHC test could successfully predict the therapeutic effects and disease prognosis.

PMID:37715423 | DOI:10.14715/cmb/2023.69.7.12

Eur J Med Res. 2023 Sep 15;28(1):350. doi: 10.1186/s40001-023-01236-x.

ABSTRACT

BACKGROUND: Skin, as a sociologically meaningful interface, has psychological implications different from other organs, particularly in the context of the global population aging. Growing evidence suggests that facial aging is associated with an increased risk of adiposity. Existing research, however, were observational, and while they may find some correlations, it is difficult to simply disentangle non-causal or reverse-causal links because these associations may be confounded or fail to accurately reflect true causative linkages.

OBJECTIVES: We conducted a 2-sample Mendelian randomization (MR) study to examine the potential effect of facial aging on the risk of broad obesity and its three major adiposity indicators, including body mass index (BMI), body fat percentage (BF%) and waist circumference (WC).

METHODS: Genetic instruments from IEU OpenGWAS project, one of the largest available genome-wide association studies (GWAS) for facial aging (423,999 samples) were used to investigate the relation to broad obesity (32,858 cases, 65,839 controls). Using the inverse-variance weighted (IVW) technique, single nucleotide polymorphisms (SNPs) associated with adiposity indicators (BMI (461,460 samples), BF% (454,633 samples), and WC (462,166 samples)) were investigated in relationship to facial aging. Further sensitivity analyses were performed, including Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, to evaluate the consistency of the results and related potential issues in MR studies.

RESULTS: We identified strong and significant correlations between adiposity and facial aging in the 17 broad obesity-associated SNPs (IVW estimate of odds ratio OR = 1.020, 95% CI 1.010-1.029, P = 7.303e – 05), 458 BMI-associated SNPs (IVW estimate of odds ratio OR = 1.047, 95% CI 1.0357-1.058, P = 1.154e – 16),for the 395 BF%-associated SNPs (OR = 1.056, 95%CI 1.040-1.072,P = 7.617e – 12), or for the 374 WC-associated SNPs (OR = 1.072, 95% CI 1057-1.087,P = 1.229e – 23). A range of complementary methodologies have been employed to evaluate horizontal pleiotropy and related potential caveats occurring in MR research.

CONCLUSIONS: Using Mendelian randomization as an alternative approach to investigate causality, we found a causal relationship between adiposity and facial aging, which was statistically strong and significant.

PMID:37715292 | DOI:10.1186/s40001-023-01236-x

J Anesth Analg Crit Care. 2023 Sep 15;3(1):34. doi: 10.1186/s44158-023-00120-8.

ABSTRACT

BACKGROUND: Septoplasty, a common surgical procedure to correct a deviated septum, can be performed under either general anesthesia or deep sedation anesthesia. The choice of anesthesia can influence the duration of anesthesia and surgical outcomes, impacting the feasibility of outpatient procedures.

METHODS: The institutional review board approved the protocol, and we obtained written informed consent from all participants. This retrospective, single-center observational study analyzed data from 586 patients who underwent rhino septoplasty at Santo Stefano Hospital in Prato, Italy, from 2017 to 2021. Patients received either general anesthesia or deep sedation anesthesia. Propensity score matching and inverse probability weighting were used to balance patient characteristics. The main outcome variable was discharge time, with anesthesia time and surgical time as covariates. Statistical analysis was conducted using R software.

RESULTS: Patients who received deep sedation anesthesia had a significantly shorter duration of anesthesia compared to those who received general anesthesia. A multivariate linear regression model showed that the type of anesthesia had a strong positive association with discharge time, while anesthesia time had a weaker negative association, although not statistically significant.

CONCLUSIONS: Deep sedation anesthesia is associated with a shorter duration of anesthesia compared to general anesthesia during nasal septal surgery, suggesting it could be a more feasible option for outpatient procedures. However, the choice of anesthesia should be tailored to individual patient factors and surgical requirements. Further research is needed to confirm these findings and explore the potential benefits of sedation anesthesia in outpatient nasal septal surgery.

QUESTION: How do general anesthesia and deep sedation anesthesia compare in terms of duration of anesthesia and surgical outcomes during nasal septal surgery?

FINDINGS: Our study found that deep sedation anesthesia was associated with a shorter duration of anesthesia compared to general anesthesia in patients undergoing nasal septal surgery. However, there were no significant differences in the duration of the surgical procedure.

MEANING: The findings suggest that deep sedation anesthesia could potentially make nasal septal surgery more feasible as an outpatient procedure.

PMID:37715286 | DOI:10.1186/s44158-023-00120-8

Pilot Feasibility Stud. 2023 Sep 15;9(1):162. doi: 10.1186/s40814-023-01387-y.

ABSTRACT

BACKGROUND: Delirium affects over 20% of all hospitalised older adults. Delirium is associated with a number of adverse outcomes following hospital admission including cognitive decline, anxiety and depression, increased mortality and care needs. Previous research has addressed prevention of delirium in hospitals and care homes, and there are guidelines on short-term treatment of delirium during admission. However, no studies have addressed the problem of longer-term recovery after delirium and it is currently unknown whether interventions to improve recovery after delirium are effective and cost-effective. The primary objective of this feasibility study is to test a new, theory-informed rehabilitation intervention (RecoverED) in older adults delivered following a hospital admission complicated by delirium to determine whether (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible.

METHODS: The study is a multi-centre, single-arm feasibility study of a rehabilitation intervention with an embedded process evaluation. Sixty participants with delirium (aged > 65 years old) and carer pairs will be recruited from six NHS acute hospitals across the UK. All pairs will be offered the intervention, with follow-up assessments conducted at 3 months and 6 months post-discharge home. The intervention will be delivered in participants’ own homes by therapists and rehabilitation support workers for up to 10 intervention sessions over 12 weeks. The intervention will be tailored to individual needs, and the chosen intervention plan and goals will be discussed and agreed with participants and carers. Quantitative data on reach, retention, fidelity and dose will be collected and summarised using descriptive statistics. The feasibility outcomes that will be used to determine whether the study meets the criteria for progression to a definitive randomised controlled trial (RCT) include recruitment, delivery of the intervention, retention, data collection and acceptability of outcome measures. Acceptability of the intervention will be assessed using in-depth, semi-structured qualitative interviews with participants and healthcare professionals.

DISCUSSION: Findings will inform the design of a pragmatic multi-centre RCT of the effectiveness and cost-effectiveness of the RecoverED intervention for helping the longer-term recovery of people with delirium compared to usual care.

TRIAL REGISTRATION: The feasibility study was registered: ISRCTN15676570.

PMID:37715277 | DOI:10.1186/s40814-023-01387-y

Trials. 2023 Sep 15;24(1):591. doi: 10.1186/s13063-023-07421-x.

ABSTRACT

BACKGROUND: About 50% of older patients with acute myeloid leukemia (AML) fail to attain complete remission (CR) following cytarabine plus anthracycline-based induction therapy. Salvage chemotherapy regimens are based on high-dose cytarabine (HiDAC), which is frequently combined with mitoxantrone (HAM regimen). However, CR rates remain low, with less than one-third of the patients achieving a CR. FLT3-ITD has consistently been identified as an unfavorable molecular marker in both relapsed and refractory (r/r)-AML. One-quarter of patients who received midostaurin are refractory to induction therapy and relapse rate at 2 years exceeds 40%. The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is a very selective FLT3 inhibitor, has a high capacity for sustained FLT3 inhibition, and has an acceptable toxicity profile.

METHODS: In this multicenter, upfront randomized phase II trial, all patients receive quizartinib combined with HAM (cytarabine 3g/m² bidaily day one to day three, mitoxantrone 10mg/m² days two and three) during salvage therapy. Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach with achievement of CR, complete remission with incomplete hematologic recovery (CRi), or complete remission with partial recovery of peripheral blood counts (CRh) as primary endpoint. During consolidation therapy (chemotherapy and allogeneic hematopoietic cell transplantation), patients receive either prophylactic quizartinib therapy or measurable residual disease (MRD)-triggered preemptive continuation therapy with quizartinib according to up-front randomization. The matched threshold crossing approach is a novel study-design to enhance the classic single-arm trial design by including matched historical controls from previous clinical studies. It overcomes common disadvantages of single-armed and small randomized studies, since the expected outcome of the observed study population can be adjusted based on the matched controls with a comparable distribution of known prognostic and predictive factors. Furthermore, balanced treatment groups lead to stable statistical models. However, one of the limitations of our study is the inability to adjust for unobserved or unknown confounders. Addressing the primary endpoint, CR/CRi/CRh after salvage therapy, the maximal sample size of 80 patients is assessed generating a desirable power of the used adaptive design, assuming a logistic regression is performed at a one-sided significance level α=0.05, the aspired power is 0.8, and the number of matching partners per intervention patient is at least 1. After enrolling 20 patients, the trial sample size will be recalculated in an interim analysis based on a conditional power argument.

CONCLUSION: Currently, there is no commonly accepted standard for salvage chemotherapy treatment. The objective of the salvage therapy is to reduce leukemic burden, achieve the best possible remission, and perform a hemopoietic stem-cell transplantation. Thus, in patients with FLT3-ITD mutation, the comparison of quizartinib with intensive salvage therapy versus chemotherapy alone appears as a logical consequence in terms of efficacy and safety.

ETHICS AND DISSEMINATION: Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03989713; EudraCT Number: 2018-002675-17.

PMID:37715270 | DOI:10.1186/s13063-023-07421-x

J Cardiothorac Surg. 2023 Sep 15;18(1):259. doi: 10.1186/s13019-023-02362-7.

ABSTRACT

OBJECTIVES: Since the introduction of surgical implantation of conduit for right ventricle-to-pulmonary artery pathway reconstruction, there has been a number of studies on possible factors which might potentially affect conduit longevity, as well as patient’s reintervention-free and overall survival. Still, no definite consensual agreement could be made thus far. We aimed to compare conduit longevity, reintervention-free survival, and overall survival between patients with congenital heart diseases indicated for operations involving right ventricle-to-pulmonary artery pathway reconstruction whose conduits were placed heterotopically to those with orthotopically placed ones.

MATERIALS AND METHODS: We retrospectively collected data from electronic medical records of Ramathibodi hospital from 1st January 2005 to 31st December 2022. Patients with congenital heart diseases whose operations involved reconstruction of right ventricle-to-pulmonary artery continuity were included. Patients whose medical record data were significantly missing were excluded. Demographic data, operative, and postoperative details were collected and reviewed.

RESULTS: There were 67 patients included in our study, with 25 receiving orthotopic and the other 42 receiving heterotopic conduit implantation. Conduit dysfunction-free, reintervention-free, and overall survival were not statistically different between both groups. There was 1 early and no late death up to the end date of our study.

CONCLUSIONS: Conduits placed on a heterotopic position did not result in worse longevity, reintervention-free survival, as well as overall survival when compared to conduits placed on an orthotopic position. This suggested that the less technically demanding heterotopic conduit placement could be recommended as an operation of choice for right ventricular outflow tract reconstruction.

PMID:37715260 | DOI:10.1186/s13019-023-02362-7

Malar J. 2023 Sep 16;22(1):275. doi: 10.1186/s12936-023-04706-z.

ABSTRACT

BACKGROUND: In 2021, Brazil was responsible for more than 25% of malaria cases in the Americas. Although the country has shown a reduction of cases in the last decades, in 2021 it reported over 139,000 malaria cases. One major malaria control strategy implemented in Brazil is the “Malaria Supporters Project”, which has been active since 2012 and is directed to municipalities responsible for most Brazil’s cases. The objective of this study is to analyse the intervention effect on the selected municipalities.

METHODS: An ecological time-series analysis was conducted to assess the “Malaria Supporters Project” effect. The study used data on Annual Parasitic Incidence (API) spanning the period from 2003 to 2020 across 48 intervention municipalities and 88 control municipalities. To evaluate the intervention effect a Prais-Winsten segmented regression model was fitted to the difference in malaria Annual Parasitic Incidence (API) between control and intervention areas.

RESULTS: The intervention group registered 1,104,430 cases between 2012 and 2020, a 50.6% reduction compared to total cases between 2003 and 2011. In 2020 there were 95,621 cases, 50.4% fewer than in 2011. The number of high-risk municipalities (API > 50 cases/1000) reduced from 31 to 2011 to 17 in 2020. The segmented regression showed a significant 42.0 cases/1000 residents annual decrease in API compared to control group.

CONCLUSIONS: The intervention is not a silver bullet to control malaria, but it has reduced API in locations with high malaria endemicity. Furthermore, the model has the potential to be replicated in other countries with similar epidemiological scenarios.

PMID:37715245 | DOI:10.1186/s12936-023-04706-z

BMC Womens Health. 2023 Sep 15;23(1):492. doi: 10.1186/s12905-023-02640-5.

ABSTRACT

BACKGROUND: The unmet need for limiting childbearing (UNLC) remains a problem in Nigeria. Conception after four pregnancies is considered a high-risk pregnancy. We examined the level, reasons for non-use of contraception, and predictors of UNLC among high parity (≥ 4 live birth) women in Nigeria.

METHODS: This cross-sectional design study was based on the analysis of nationally representative weighted data (2018 Nigeria Demographic Health Survey). The study focused on high-parity women of reproductive age (n = 4260) who do not want to have any more children irrespective of the number of their surviving children. Multi-stage cluster sampling approach was used for sample selection. Data were analyzed using logistic regression (α_0.05).

RESULTS: Mean age of the respondents and children ever born was 38.92 ± 5.7 and 6.54 ± 2.3 respectively. The prevalence of UNLC was 40.9%, higher in the rural (48.8%) than urban (32.8%) areas, highest among women with no formal education (52.0%), higher among Muslims (48.4%) than Christians (34.8%), highest in the North-West (51.7%) and least in the South-East (26.1%). The most reported reasons for non-use of family planning (FP) were; respondents opposed (25.0%), infrequent sex (15.0%), fatalistic (13.2%), husband/partner opposed (11.2%), fear of side effects/health (8.5%), and religious prohibition (3.3%). The odds of UNLC was 100% higher among women aged 40-49 years compared to the younger women in age group 20-29 years. Living in the rural area predisposes high parity women of reproductive age to higher risks of UNLC (OR = 1.35, 95% C.I = 1.14-1.59, p < 0.001). Lack of access to family planning information through health workers (OR = 1.94, 95% C.I = 1.63-2.30, p < 0.001) increased the risks of UNLC. Being an Igbo or a Yoruba ethnic group was protective for UNLC compared to Fulani/Hausa women.

CONCLUSIONS: A high level of UNLC was found among high-parity women in Nigeria. Access to FP information reduces the risk of UNLC. Expanding FP services would help respond to the expressed desires for contraception among high-parity Nigerian women who want to stop childbearing.

PMID:37715218 | DOI:10.1186/s12905-023-02640-5

J Anesth Analg Crit Care. 2023 Sep 15;3(1):35. doi: 10.1186/s44158-023-00114-6.

ABSTRACT

BACKGROUND: Four-hundred forty-nine patients affected by Covid-19 were hospitalized at the Rome Military Hospital between March 2020 and July 2022. Depending on the severity of the disease, they were assigned either to the Functional Health Emergency Unit – if suffering from interstitial pneumonia with a clinical manifestation of dyspnea associated with peripheral oxygen saturation < 92%, and oxygen atmospheric pressure therapy – or to the intensive care unit – if the blood gas-lytic index P/F (ratio between partial pressure of arterial O2 and inspired fraction of O2) was below 150. This prospective observation and monocentric study aim to verify the outcome (healing/death) of early use of remdesivir in pneumonia patients.

RESULTS: The results highlight the importance of the adoption of remdesivir in the initial stages of infection to prevent the systemic spread and viral multiplication and, in the subsequent phase, a cytokine storm resulting in acute respiratory failure and multiorgan failure. The use of the drug in the most advanced stages of the disease is not associated with a real impact on patient outcomes. Therefore, there is a statistically significant correspondence between the early use of remdesivir in the treatment of SARS-CoV-2 disease – in addition to guidelines therapies – and a favorable clinical outcome.

CONCLUSIONS: This work shows therapeutic efficacy in the first 5 days of intravenous administration of remdesivir, following the loading dose. It is also necessary to underline the different behaviors of the drug when administered late in patients undergoing mechanical ventilation, compared to those who only needed low-flow oxygen therapy, whose share of recovery – decidedly relevant – reaches statistical significance.

PMID:37715210 | DOI:10.1186/s44158-023-00114-6

J Transl Med. 2023 Sep 15;21(1):626. doi: 10.1186/s12967-023-04450-7.

ABSTRACT

BACKGROUND: Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the treatment of advanced cholangiocarcinoma and more recently for relapsed or refractory myeloid/lymphoid neoplasms with FGFR2 and FGFR1 rearrangements, respectively. Several clinical trials are currently investigating the possible combination of pemigatinib with immunotherapy. In this study, we analyzed the biological and molecular effects of pemigatinib on different cancer cell models (lung, bladder, and gastric), which are currently objective of clinical trial investigations.

METHODS: NCI-H1581 lung, KATO III gastric and RT-112 bladder cancer cell lines were evaluated for FGFR expression by qRT-PCR and Western blot. Cell lines were treated with Pem and then characterized for cell proliferation, apoptosis, production of intracellular reactive oxygen species (ROS), and induction of senescence. The expression of microRNAs with tumor suppressor functions was analyzed by qRT-PCR, while modulation of the proteins coded by their target genes was evaluated by Western blot and mRNA. Descriptive statistics was used to analyze the various data and student’s t test to compare the analysis of two groups.

RESULTS: Pemigatinib exposure triggered distinct signaling pathways and reduced the proliferative ability of all cancer cells, inducing G1 phase cell cycle arrest and strong intracellular stress resulting in ROS production, senescence and apoptosis. Pemigatinib treatment also caused the upregulation of microRNAs (miR-133b, miR-139, miR-186, miR-195) with tumor suppressor functions, along with the downregulation of validated protein targets with oncogenic roles (c-Myc, c-MET, CDK6, EGFR).

CONCLUSIONS: These results contribute to clarifying the biological effects and molecular mechanisms mediated by the anti-FGFR TKI pemigatinib in distinct tumor settings and support its exploitation for combined therapies.

PMID:37715207 | DOI:10.1186/s12967-023-04450-7