Stringent Inclusion Criteria Research Articles

Evaluating the Efficacy and Safety of Therapeutic Interventions in Sjögren's Syndrome: A Systematic Review Literature.

In strict accordance with PRISMA 2020 guidelines, our research team conducted a comprehensive systematic literature review (SLR) to explore the treatment and preventive strategies for Sjögren's Syndrome (SS). Leveraging a meticulous search strategy, we scoured reputable databases such as PubMed, PubMed Central, Google Scholar, Web of Science, and The Cochrane Library. Our analysis zeroed in on 10 seminal articles that met our stringent inclusion criteria, providing a holistic view of the existing treatment landscape for SS, along with emerging diagnostic tools and associated biomarkers indicative of lymphoma risk. From a clinical standpoint, our findings unequivocally highlight the detrimental effects of SS on patients' overall well-being. Of particular interest is the growing body of evidence that underscores the effectiveness of natural remedies and over-the-counter supplements rich in antioxidants as viable therapeutic interventions. Contrary to expectations, no single laboratory marker emerged as highly sensitive for the diagnosis of SS. On a promising note, dental implants have been demonstrated to offer lasting benefits with minimal side effects, emphasizing their potential utility in enhancing the oral health of individuals affected by SS. Given the evolving nature of treatment approaches for SS, our review strongly calls for further investigations. Such research endeavors are imperative for validating the effectiveness of these treatment options, whether they serve as primary or preventive care solutions, with the overarching aim of improving the quality of oral health among those suffering from SS.

Automated advanced imaging in acute ischemic stroke. Certainties and uncertainties

The purpose of this is study was to review pearls and pitfalls of advanced imaging, such as computed tomography perfusion and diffusion-weighed imaging and perfusion-weighted imaging in the selection of acute ischemic stroke (AIS) patients suitable for endovascular treatment (EVT) in the late time window (6–24 h from symptom onset). Advanced imaging can quantify infarct core and ischemic penumbra using specific threshold values and provides optimal selection parameters, collectively called target mismatch. More precisely, target mismatch criteria consist of core volume and/or penumbra volume and mismatch ratio (the ratio between total hypoperfusion and core volumes) with precise cut-off values. The parameters of target mismatch are automatically calculated with dedicated software packages that allow a quick and standardized interpretation of advanced imaging. However, this approach has several limitations leading to a misclassification of core and penumbra volumes. In fact, automatic software platforms are affected by technical artifacts and are not interchangeable due to a remarkable vendor-dependent variability, resulting in different estimate of target mismatch parameters. In addition, advanced imaging is not completely accurate in detecting infarct core, that can be under- or overestimated. Finally, the selection of candidates for EVT remains currently suboptimal due to the high rates of futile reperfusion and overselection caused by the use of very stringent inclusion criteria. For these reasons, some investigators recently proposed to replace advanced with conventional imaging in the selection for EVT, after the demonstration that non-contrast CT ASPECTS and computed tomography angiography collateral evaluation are not inferior to advanced images in predicting outcome in AIS patients treated with EVT. However, other authors confirmed that CTP and PWI/DWI postprocessed images are superior to conventional imaging in establishing the eligibility of patients for EVT. Therefore, the routine application of automatic assessment of advanced imaging remains a matter of debate. Recent findings suggest that the combination of conventional and advanced imaging might improving our selection criteria.

Contractor Perspective on Overcoming Cost Consideration as a Barrier to Using Sustainable Building Materials in Affordable Housing: A Systematic Review

The construction industry greatly contributes to environmental degradation, and sustainable building materials are becoming more important in minimizing this impact. However, the construction industry, especially affordable housing projects, confronts several obstacles that make it difficult to employ sustainable building materials widely. Many studies have investigated and advocated various barriers to using sustainable building materials within the construction industry. However, no attention has been paid to the cost consideration barrier for using sustainable building materials in Malaysia's affordable housing. In light of these challenges, This paper presents a systematic literature review that takes a broad approach, includes stringent inclusion and exclusion criteria, a thorough search strategy that includes a variety of databases and additional sources, a strict study selection procedure with multiple reviewers, quality assessment of included studies, and a narrative synthesis of findings focusing on several strategies for overcoming the cost consideration issues in using sustainable building materials in Malaysia's affordable housing from a contractor perspective. This study is important to improve affordable houses’ costs and ensure their residents’ comfort. By implying these strategies, Contractors may reduce costs and encourage sustainable construction materials in affordable housing projects.

Detection of Biochemically Recurrent Prostate Cancer with [18F]DCFPyL PET/CT: An Updated Systematic Review and Meta-Analysis with a Focus on Correlations with Serum Prostate-Specific Antigen Parameters.

[18F]DCFPyL is increasingly used for prostate-specific membrane antigen (PSMA) mediated imaging of men with biochemically recurrent prostate cancer (BRPCa). In this meta-analysis, which is updated with the addition of multiple new studies, including the definitive phase III CONDOR trial, we discuss the detection efficiency of [18F]DCFPyL in BRPCa patients. PubMed was searched on 29 September 2022. Studies evaluating the diagnostic performance of [18F]DCFPyL among patients with BRPCa were included. The overall pooled detection rate with a 95% confidence interval (95% CI) was calculated among all included studies and stratified among patients with PSA ≥ 2 vs. <2 ng/mL and with PSA ≥ 0.5 vs. <0.5 ng/mL. The association of detection efficiency with pooled PSA doubling time from two studies was calculated. Seventeen manuscripts, including 2252 patients, met the inclusion criteria and were used for data extraction. A previous meta-analysis reported that the pooled detection rate was 0.81 (95% CI: 0.77-0.85), while our study showed a pooled overall detection rate of 0.73 (95% CI: 0.66-0.79). An increased proportion of positive scans were found in patients with PSA ≥ 2 vs. <2 ng/mL and PSA ≥ 0.5 vs. <0.5 ng/mL. No significant difference was found in detection efficiency between those with PSA doubling time ≥ 12 vs. <12 months. Detection efficiency is statistically related to serum PSA levels but not to PSA doubling time based on available data. The detection efficiency of [18F]DCFPyL in men with BRPCa has trended down since a previous meta-analysis, which may reflect increasingly stringent inclusion criteria for studies over time.

The Effect of Probiotic Supplementation on Glucolipid Metabolism in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Type 2 diabetes mellitus (T2DM) is a persistent metabolic condition with an unknown pathophysiology. Moreover, T2DM remains a serious health risk despite advances in medication and preventive care. Randomised controlled trials (RCTs) have provided evidence that probiotics may have positive effects on glucolipid metabolism. Therefore, we performed a meta-analysis of RCTs to measure the effect of probiotic therapy on glucolipid metabolism in patients with T2DM. With no constraints on the language used in the literature, Excerpta Medica Database, PubMed, the Cochrane Library, and the Web of Science were searched for pertinent RCTs published between the date of creation and 18 August 2022. Stringent inclusion and exclusion criteria were applied by two reviewers to independently examine the literature. The risk of bias associated with the inclusion of the original studies was assessed using the Cochrane risk-of-bias tool, and Stata 15.0 was used to perform the meta-analysis. Thirty-seven publications containing a total of 2502 research participants were included in the meta-analysis. The results showed that after a probiotic intervention, the experimental group showed a significant decrease in body mass index (standardised mean difference (SMD) = -0.42, 95% confidence interval (CI) [-0.76, -0.08]), fasting glucose concentration (SMD = -0.73, 95% CI [-0.97, -0.48]), fasting insulin concentration (SMD = -0.67, 95% CI [-0.99, -0.36]), glycated haemoglobin concentration (SMD = -0.55, 95% CI [-0.75, -0.35]), Homeostatic Model Assessment for Insulin Resistance score (SMD = -0.88, 95% CI [-1.17, -0.59]), triglyceride concentration (SMD = -0.30, 95% CI [-0.43, -0.17]), total cholesterol concentration (SMD = -0.27, 95% CI [-0.43, -0.11]), and low-density lipoprotein concentration (SMD = -0.20, 95% CI [-0.37, -0.04]), and an increase in high-density lipoprotein concentration (SMD = 0.31, 95% CI [0.08, 0.54]). Moreover, subgroup analyses showed that patients with a longer intervention time, or those who were treated with multiple strains of probiotics, may benefit more than those with a shorter intervention time or those who were treated with a single probiotic strain, respectively. Probiotic supplementation improves glucolipid metabolism in patients with T2DM, offering an alternative approach for the treatment of these patients.

Impact of AI and COVID-19 on manufacturing systems: An Asia Pacific Perspective on the two Competing exigencies

ABSTRACT COVID-19 pandemic underscored reliance upon technology as the singular solution to many of humanity’s banes and provided impetus to Artificial Intelligence (AI). The unprecedented advent of COVID-19 posited several impediments to public health and welfare, and manufacturing systems in the Asia-Pacific (APAC) region. The primary intent of this study is to investigate the symbiotic influence of AI and COVID-19 on the job market of the APAC region and entailing volatility. This study exames the shift in demand for various technical skills with increased adoption of AI. Review of existing literature scrutinized the research questions, and the analysis revealed a significant increase in new tasks being taken over by AI. The methodology deployed in this study includes a systematic literature review protocol together with stringent inclusion and exclusion criteria to filter articles and data. An interpretivist philosophy, foregrounded in an inductive case-study approach ensemble the analysis and conclusion of the study.

Amiodarone-Induced Myxedema Coma in Elderly Patients: A Systematic Review of Case Reports.

This systematic review aimed to explore whether elderly patients administered amiodarone were susceptible to developing myxedema coma. Utilizing the Cochrane guidelines, a comprehensive review of databases such as Medline (PubMed), Science Direct, CINAHL Cochrane, and Google Scholar was undertaken to examine case reports on amiodarone-induced myxedema coma. Following stringent criteria for inclusion, 12 pertinent case reports were identified. These findings suggested a high probability of myxedema coma development in patients who had been administered amiodarone. Specifically, patients who received an oral dosage of 100-200 mg of amiodarone were reported to have developed bradycardia and hypothermia alongside elevated thyroid-stimulating hormone (TSH) levels. Upon diagnosis, the majority of patients were treated with a regimen of levothyroxine and hydrocortisone medication. Despite the myriad potential causes of myxedema coma complicating the diagnosis, it was found that through a combination of clinical symptoms and serum TSH measurements, a confirmed diagnosis could be reached. Furthermore, it was observed that amiodarone-induced myxedema coma responded favorably to treatment with levothyroxine and glucocorticoids.

Real-World Evidence Studies in Oncology Therapeutics: Hope or Hype?

Randomized controlled trial (RCT) remains a gold standard in evidence-based medicine for assessing the efficacy and safety of cancer therapies. However, due to some inherent methodological limitations of RCT, such as stringent inclusion criteria, highly specific treatment, ethical and scientific compromise in rare cancer, and inability to adequately assess safety, real-world evidence (RWE) has been adjudged as a suitable option to complement data obtained from RCT. Moreover, in the context of cancer therapeutics, few notable merits pertain to developing a novel product for rare cancer subtypes, establishing new indications for already approved drugs, optimization of treatment regimen and sequence, a better description of long-term safety, and supporting the reimbursement-related decision. However, the implementation of RWE for the aforementioned purposes will be limited by various challenges, especially in the context of developing economies such as India. Special attention should be given to the availability of data, maintaining the quality standard, and establishing stringent regulations for privacy and security along with active regulatory engagement with relevant stakeholders. Such activities will be key to facilitating the use of RWE in cancer therapeutics.

REALMA: Subset of patients with Marginal Zone Lymphomas from the French nationwide REALYSA real‐world prospective cohort.

Background: Marginal Zone Lymphomas (MZL) are a heterogeneous group of lymphomas that include three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since most of the knowledge comes from clinical trials (with stringent inclusion criteria and limited representativeness), there is a crucial need for real-world evidence in MZL. In 2018 the French REALYSA (Real world dAta in LYmphoma in Adults) study was initiated as a nationwide multicentric prospective cohort of patients newly diagnosed with lymphoma. By Dec 31, 2021, a total of 207 patients with MZL were included in the study. Methods: Patients were recruited in 35 French hematology centers and received routine care. Data were collected from medical records and questionnaires. A first abstraction was performed on Jan 1, 2023, to parse out the available data regarding MZL patients with >1 year of follow-up. Each case was reviewed by medical and pathological experts, and treatments were classified on an intent-to-treat basis. Results: Of the 207 patients with MZL included up to Dec 31, 2021, 111 (53%) presented with EMZL, 47 (23%) with SMZL and 49 (24%) with NMZL. At baseline, median age was of 67 years old (IQR 60,75), 53% of patients were females, 5.5% of patients had a PS of 2–4, 70% were stage III-IV, 19% presented with B-symptoms, 20% had a bulky mass >7 cm and 5.8% had a compressive syndrome. Only 7% of patients reported an auto-immune disease. Diagnosis of MZL was mostly evoked by general practitioners (48%) but patients were finally treated by hematologists (98%). Only 9 patients were referred to an onco-geriatrician. Regarding the initial workup, while at least one imagery was offered in 97% of patients, 18FDG-PET/CT (EMZL 78%, SMZL 62%, NMZL 78%) was performed more frequently than CT-scan at baseline (EMZL 73%, SMZL 62%, NMZL 71%), although 47% patients underwent both procedures. Among the 207 patients, 58 (28%) were not treated. Only 10 patients exclusively received local therapy (radiotherapy n = 6, surgery n = 2, antibiotics n = 2). Regarding systemic therapies, rituximab-chlorambucil was mainly offered in patients with EMZL (40%), while rituximab-monotherapy was preferred in SMZL (60%). For patients with NMZL, physicians mainly offered RCHOP (33%) and rituximab-bendamustine (27%). Only 7 patients with EMZL received the combination of ibrutinib and rituximab. At end of 1st line, 93% of patients had responded to therapy and 75% were in complete response. Among patients assessed with 18FDG-PET/CT, a metabolic complete response was observed in 52/58 (90%) of cases. Conclusion: This is the first analysis describing real-world data of patients with MZL in France. Our cohort features high-quality data both on epidemiological and clinical outcomes. When the total number of patients will increase and data will mature, this dataset will provide insightful information regarding both endpoints and treatment evaluations. Keyword: Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. C. Bommier Research funding: Inserm/AvieSan/ITMO Cancer, LYSA/ELI (Bertrand Coiffier Prize), Philippe Foundation, Institut Servier

Choosing the Best Design in Surgical Research.

Choosing the Best Design in Surgical Research.

Volumetric hippocampal changes in glioblastoma: a biomarker for neuroplasticity?

PurposeThe pleiotropic effect of gliomas on the development of cognitive disorders and structural brain changes has garnered increasing interest in recent years. While it is widely accepted that multimodal therapies for brain cancer can foster cognitive impairment, the direct effect of gliomas on critical cognitive areas before anti-tumor therapies is still controversial. In this study, we focused on the effect of IDH1 wild-type glioblastoma on the human hippocampus volume.MethodsWe carried out a case-control study using voxel-based morphometry assessment, analyzed with the Computational Anatomy Toolbox software. Glioblastoma diagnosis was performed according to the latest 2021 WHO classification. Due to stringent inclusion criteria, 15 patients affected by IDH1 wild type glioblastoma were included and compared to 19 age-matched controls.ResultsWe observed a statistically significant increase in the absolute mean hippocampal volume (p = 0.017), as well as in the ipsilateral (compared to the lesion, p = 0.027) and the contralateral hippocampal volumes (p = 0.014) in the group of patients. When the data were normalized per total intracranial volume, we confirmed a statistically significant increase only in the contralateral hippocampal volume (p = 0.042).ConclusionsTo the best of our knowledge, this is the first study to explore hippocampal volumetric changes in a cohort of adult patients affected by IDH1 wild-type glioblastoma, according to the latest WHO classification. We demonstrated an adaptive volumetric response of the hippocampus, which was more pronounced on the side contralateral to the lesion, suggesting substantial integrity and resilience of the medial temporal structures before the initiation of multimodal treatments.

A comparative study to assess the weight gain among breast-fed, formula-fed and mix-fed preterm babies

Body weight is a crucial indicator of a baby's development and growth. The connection between nursing and body weight is extremely important for the health of newborns. This study compares the weight gain among breastfed, formula-fed, and mixed-fed preterm babies (weight between 1-2 kilograms) admitted to the neonatal ICU of the Indraprastha Apollo hospital in New Delhi. Thirty-five newborn babies, ranging in age from 28 to 35 weeks, with a weight of 1-2 kg, were selected using the purposive sampling technique. The data collection was done for 3 months, from August to October 2022, by biomarkers and in vivo weight measurement. The weight was assessed for 17 days following the commencement of the first feed, and the weight was measured at the same time every day. The demographic characteristics of the sample revealed that 54.28 percent of the newborns included in the study were born in Apollo hospitals. Out of 35 babies, 31 were born through a cesarean session and the remaining four through a complicated vaginal delivery. The majority of the babies are between 34 and 35 weeks of gestation. The most common maternal complications observed were hypertension and oligohydramnios, and only a few neonates had fetal complications. The inferential analysis showed that there was no significant weight gain among the three categories during the first 17 days of feeding. The study can be repeated in different settings with more stringent inclusion criteria and for a longer duration.

Remote Patient Monitoring for Patients with Heart Failure: Sex- and Race-based Disparities and Opportunities.

Remote patient monitoring (RPM), within the larger context of telehealth expansion, has been established as an effective and safe means of care for patients with heart failure (HF) during the recent pandemic. Of the demographic groups, female patients and black patients are underenrolled relative to disease distribution in clinical trials and are under-referred for RPM, including remote haemodynamic monitoring, cardiac implantable electronic devices (CIEDs), wearables and telehealth interventions. The sex- and race-based disparities are multifactorial: stringent clinical trial inclusion criteria, distrust of the medical establishment, poor access to healthcare, socioeconomic inequities, and lack of diversity in clinical trial leadership. Notwithstanding addressing the above factors, RPM has the unique potential to reduce disparities through a combination of implicit bias mitigation and earlier detection and intervention for HF disease progression in disadvantaged groups. This review describes the uptake of remote haemodynamic monitoring, CIEDs and telehealth in female patients and black patients with HF, and discusses aetiologies that may contribute to inequities and strategies to promote health equity.

Platelet Aggregation in Apparently Healthy Elderly Populations: Reference Ranges and Influence of Hematology Parameters.

Reference intervals based on younger populations may not apply to elderly populations. The aim of the current study was to calculate reference ranges for platelet aggregation in apparently healthy Chinese elderly populations and analyze the impact of gender, age, and hematological parameters on platelet aggregation in vitro. A total of 138 males and 161 females were enrolled based on stringent inclusion and exclusion criteria. Platelet aggregation was measured with sodium citrate anticoagulation whole blood samples using a PL12 analyzer, triggered by adenosine-5'-diphosphate (ADP) and arachidonic acid (AA) agonists. Hematological parameters were measured using a Sysmex XE2100 instrument. In the total sample tested in this study, the platelet aggregation induced by AA and ADP was not dependent on age (p > 0.05) but gender. Platelet aggregation triggered by ADP and AA was more enhanced in females than males (p = 0.024 for AA, p = 0.036 for ADP). The recommended reference values of AA-induced platelet aggregation were 48.42% - 85.93% for males and 43.62% - 87.80% for females. The recommended reference values of ADP-induced platelet aggregation were 38.12% - 80.21% for males and 40.12% - 83.05% for females. Furthermore, for all agonists, a positive correlation was found between platelet aggregation and platelet count. The ADP-triggered aggregation showed a significant positive correlation with white blood cell (WBC) count and a negative correlation with red blood cell (RBC) count. Moreover, platelet aggregation showed no significant correlation with mean platelet volume or hemoglobin concentration. Combined and gender-specific reference ranges for platelet aggregation in healthy elderly populations were established in whole blood measured by a sequential platelet counting method.

LEADING DRILLING INNOVATIONS FOR SUSTAINABLE OIL PRODUCTION: TRENDS AND TRANSFORMATIONS

This scholarly review delves into the realm of drilling innovations within the oil industry, with a particular focus on the integration and advancement of sustainable practices. The primary purpose of this study is to dissect the evolution of oil drilling technologies, assess the burgeoning role of sustainability in oil production, and identify existing research gaps in sustainable drilling practices. Employing a meticulous literature review methodology, the study systematically sifts through a plethora of peer-reviewed sources, adhering to stringent inclusion and exclusion criteria to ensure the relevance and focus of the analysis. The findings of this review are illuminating, revealing a significant shift in the oil drilling landscape towards sustainability. It traces the historical development of drilling techniques, underscoring the technological strides that have revolutionized the industry. A key revelation is the ascendancy of sustainability as a pivotal concern, with innovations increasingly aimed at reducing environmental impacts while bolstering economic efficiency. The review also highlights notable gaps in current literature, especially in the context of recent technological advancements and their sustainable implications. The study accentuates the critical importance of sustainable drilling innovations in the oil industry. It advocates for ongoing research and development to bridge the identified gaps and keep abreast of technological progress. The review recommends a synergistic approach involving diverse industry stakeholders to promote sustainable practices and emphasizes the need for robust policy frameworks and regulatory measures to guide the industry towards a sustainable trajectory. This review serves as an essential resource for industry stakeholders, providing comprehensive insights and directions for future research and practices in sustainable drilling innovations.

Dengue virus encephalitis: A systematic review and critique

Background &amp; Objective: Neurological manifestations were reported in dengue fever. We hypothesize that the diagnosis of DEN virus (DENV) encephalitis based on current clinical diagnostic criteria has been made too liberally. We conducted a systematic review of the literature to clarify this, and to characterize DENV encephalitis better. Methods: We systematically review the literature using MEDLINE and PubMed databases papers published from 1st January 1960 to 31st March 2020. We grouped the cases into definite and probable DENV encephalitis. Definite DENV encephalitis required demonstration of DENV (live virus, viral antigens, RNA) in the central nervous system or CSF whereas probable DENV encephalitis required positive anti-DENV IgM in the CSF and evidence of virus or anti-DENV IgM in the serum. Results: Of the 230 publications obtained from literature search, 121 case reports and series appeared relevant to DENV encephalitis. After applying our inclusion criteria, only 42 cases (34.7%) were acceptable as DENV encephalitis: 30 (24.8%) definite and 12 (9.9%) probable cases. Our findings suggest that DENV encephalitis is more uncommon than previously thought. Part of the reason for non-inclusion may be because many studies relied solely on DENV serology for diagnosis. Cross-reactivities of anti-DENV with anti-JE virus immunoglobulins in serum or CSF occur and this limits their usefulness to distinguish DENV encephalitis from JE. Conclusions: The majority of DENV encephalitis cases reported in the literature did not satisfy a more stringent inclusion criteria. Further investigations including autopsy studies are warranted to better characterize and to understand the pathology and pathogenesis of DENV encephalitis.

Keller Funnel Efficacy in "No Touch" Breast Augmentation and Reconstruction: A Systematic Review.

A systematic review of PubMed, Embase, the Cochrane database, and Google Scholar was performed between 2005 and 2021. All clinical-based, retrospective and prospective studies utilizing the Keller funnel method for breast implant insertion were selected. Six studies were identified for evaluation: five were retrospective cohorts and one was a prospective trial. No randomized controlled trials were found. Outcomes reported included lower rates of capsular contracture (RR, 0.42; P = 0.0006; 95% CI, 0.25-0.69), shorter incision lengths (35.5 ± 2.1 mm), less insertion time (mean = 6 seconds), and decreased complications, and one paper reported ultimately greater patient satisfaction with outcomes (BREAST-Q Score: 92%). This review suggests that the Keller funnel is a useful method for no-touch breast augmentation and reconstruction surgery. The Keller funnel reduces subsequent capsular contracture rate, surgical time, and incision length and allows for easier insertion. However, our findings support recommendation of a prospective randomized controlled clinical trial with larger population size and follow-up intervals.

A best-evidence meta-analysis of the effects of digital monitoring tools for teachers on student achievement

ABSTRACT In this study the effects of the use of digital student monitoring tools for teachers (DMTs) on student achievement (primary and secondary schools, mathematics, reading, and language) were investigated through a meta-analysis (n = 14). The studies were also coded for feedback and intervention features, which resulted in three groups of combinations of DMTs and interventions. The meta-analytic findings indicate that the use of a DMT overall has a moderate effect (ES = .12) on student achievement for studies in which student achievement is measured by means of researcher-independent tests. Positive effects were also found for the use of DMTs in primary education (ES = .14), reading (ES = .17), mathematics (ES = .10), and for two groups of DMT-intervention combinations (ES = .25 and .13). Our results are encouraging but should be interpreted with caution, given the small number of studies that met our stringent inclusion criteria.

Hypertension and mortality in SARS-COV-2 infection: A meta-analysis of observational studies after 2 years of pandemic

BackgroundThe worldwide pandemic SARS-CoV-2 infection is associated with clinical course including a very broad spectrum of clinical manifestations, including death. Several studies and meta-analyses have evaluated the role of hypertension on prognosis, but with important limitations and conflicting results. Therefore, we decided to perform a new meta-analysis of the observational studies that explored the relationship between pre-existing hypertension and mortality risk in patients with SARS-CoV-2 infection, using more stringent inclusion criteria to overcome the limitations inherent previous meta-analyses. MethodsA systematic search of the on-line databases available up to 31 March 2022 was conducted, including peer-reviewed original articles, involving the adult population, where the role of hypertension on mortality due to SARS-CoV-2 infection was determined by Cox-proportional hazard models. Pooled hazard ratio (HR) was calculated by a random effect model. Sensitivity, heterogeneity, publication bias, subgroup and meta-regression analyses were performed. ResultsTwenty-six studies (222,083 participants) met the pre-defined inclusion criteria. In the pooled analysis, pre-existing hypertension was significantly associated with mortality due to SARS-CoV-2 infection, both in unadjusted and adjusted models (HR: 1.55; 95% CI: 1.22 to 1.97). However, in separate analyses including results adjusted for crucial and strong predictors of mortality during SARS-CoV-2 infection (e.g. body weight), the association disappeared. ConclusionsThe results of this meta-analysis indicate that pre-existing hypertension is not an independent predictor of mortality during SARS-CoV-2 infection. Further studies should nevertheless be carried out worldwide to evaluate this role, independent of, or in interaction with, other confounders that may affect the mortality risk.

CD19-CAR-T Cells Are Effective and Safe Treatment of Post-Transplant Relapse in Pediatric and Young Adult Patients with B-Lineage ALL: Real-World Data from Germany

Introduction: Patients with precursor-B acute lymphoblastic leukemia (pre-B ALL) which have relapsed subsequent to allogeneic hematopoietic stem cell transplantation (HSCT), have relapsed twice, or were resistant to upfront therapy have a dismal prognosis. CD19-directed chimeric antigen receptor (CAR) T cells have evolved as potent immune therapy for such patients. Tisagenlecleucel (Tisa-cel) is a commercial CD19-directed autologous CAR-T cell product. The CAR contains the co-stimulatory element 4-1BB to promote in vivo persistence and proliferation. Thus this therapy is in principle competent to serve as a stand-alone therapy. Based on the results of the ELIANA trial (Maude et al. NEJM 2017), Tisa-cel was approved by FDA and EMA for pediatric/young adult B-ALL in 2017 and 2018. In clinical trials, stringent inclusion criteria narrow down the risk profiles of trial subjects. Treatment in clinical trials provides close guidance to physicians and patients during the trial. However, post approval reality leads to treatment of patients with higher and more variable risk profiles treated in many centers. With approval by the local ethics committees, we performed a retrospective study asking all CAR T cell centers in Germany approved for treatment with Tisa-cel (Kymriah®) to provide treatment data reflecting post approval reality, in order to identify patients who might most benefit from this novel, complex and expensive treatment. Patients: Twenty-one centers included all pediatric and young adult patients with pre-B ALL (n=81) who had received Tisa-cel between 8/2018-1/2022, allowing for a minimal follow-up of 5 months of surviving patients. Median age was 11.5 years (range: 1.0-25.0 years), 53 (65.4%) were male and 28 (34.6%) female, median body weight was 41.6 kg (range: 8.0 kg-135 kg). 65 patients (80.2%) had relapsed after HSCT, 15 (18.5%) had suffered a 2nd relapse without HSCT and 1 had primary refractory disease. For bridging therapy, 3 patients (3.7%) received Blinatumomab, 4 (4.9%) inotuzumab, 72 (88.9%) received low-dose chemotherapy. One patient was bridged with a high-dose chemotherapy; 1 patient with extra-medullary disease did not receive any bridging therapy. Results: Cytokine release syndrome (CRS) was observed in 55 (67.9%) patients (grade I-II: n=50, Grade III-IV: n=4 and grade V: n=1); immune cell-associated neurological syndrome (ICANS) was seen in 6 (7.4%) patients (grade I: n=2, grade III-IV: n=4). At day 28, 72 patients (88.9%) were in CR, 8 (9.9%) in NR. One patient (1.2%) succumbed to CRS. At last follow-up, 42 patients (60%) remained in remission, 34 patients had relapsed, 1 died of TRM, 3 of NRM, 1 had developed secondary MDS. This translated into an event-free survival probability (pEFS) of 43.9% (±6.5), an of overall survival (pOS) of 52.9% (±7.0), and a cumulative incidence of relapse (CIR) of 48.8% (±6.4) at 2 years post CAR T cell transfusion. CIR CD19 neg. was 33.8% (±6.1%) and CIR CD19 pos. was 15% (±4.2%). Interestingly, there was no difference between children and adult patients with regard to pEFS and pOS. A trend towards a higher pEFS (n=16, 55.0±12.7%) compared to patients receiving CAR-T for relapse after alloHSCT (n=65, 41.8±7.2%) was observed (p=0.630). Time to relapse after HSCT was a strong predictor for outcome. Patients relapsing within 6 months of HSCT had a pEFS (pOS) of 17.2±9.6% (15.6±9.6%), pEFS (pOS) for those relapsing later was 53.8±9.0% (74.5±8.0%) p=0.001), Figure 1. Risk factors: For the subgroup with post HSCT relapse, multivariable Cox-regression analysis considering age, time from HSCT to relapse, extra-medullary relapse, remission status at start of lymphodepleting chemotherapy (LDC) and LDC dosing revealed that time from HSCT to relapse >6 months’ post HSCT as a single factor reduced the risk to 0.381 and 0.221, respectively (p=0.001 and p=0.003), Table 1. Conclusion: In our analysis providing the first real-world experience in a patient cohort highly enriched for patients with post HSCT relapse, 40% of ALL patients with poor prognosis were rescued with a single dose of Tisa-cel. Our novel finding that patients post HSCT had a far better EFS if relapse occurred beyond 6 months might be attributable to more competent T-cell system with more native T-cells with higher plasticity for proliferation, expansion and persistence. This is currently a matter of investigation and may in future allow to implement strategies to optimize CAR T cell therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal