Expression pattern analysis of the long non-coding RNAs (TINCR, RP11-573D15.8, RP11-156E8.1), and their target genes (AKT1, FOXO1 and MAPK3) in patients with HIV infection, and elite controllers.

Elite controllers (ECs) defined as a small subclass of subjects with HIV capable of controlling human immunodeficiency virus (HIV) replication in the lack of antiretroviral treatment. One class of RNA molecules that serve as vital components in the network of HIV-related transcriptional regulation, are long noncoding RNAs (lncRNAs). The critical part that they take is in transcriptional regulation of HIV through monitoring various cellular signaling pathways. Reportedly, AKT and MAPK signaling pathways serve a crucial role in modulation of HIV infection. In the current investigation, we utilized bioinformatics tools to predict the lncRNAs that have the ability to interact with MAPK3, AKT, and FOXO1. Then, PBMC expression levels of lncRNAs and their target genes (AKT, FOXO1 and MAPK3) measured in the ECs (n = 15), HIV-positive (n = 40) patients and healthy control subjects (n = 40). We found a significant increase and decrease in the level of AKT and FOXO1 expression within the ECs group, respectively than in the HIV + group (P-value <0.0001 and 0.04, respectively). In the ECs group, the level of TINCR and RP11-156E8.1 was overexpressed compared to the HIV + group (P-value: 0.004 and 0.001, respectively). While RP11-573D15.8 level in ECs exhibited a significant suppression in contrast to HIV + group (P-value: 0.02). According to the receiver-operating characteristic (ROC) curve results, AKT and TINCR could serve as useful biomarkers for screening ECs groups from HIV + patients and healthy control groups. Overall, different expression patterns of selected factors and ROC curve results showed these factors could critically contribute to HIV controlling and be considered as diagnostic markers for ECs from HIV + samples.

Measuring and Managing Healthcare Supply and Demand in Real-Time.

Measuring the supply and demand for access to and wait-times for healthcare is key to managing healthcare services and allocating resources appropriately. Yet, few jurisdictions in distributed, socialized medicine settings have any way to do so. In this paper, we propose the requirements for a jurisdictional patient scheduling system that can measure key metrics, such as supply of and demand for regulated health care professional care, access to and wait times for care, real-time health system utilization and provide the data to compute patient journeys. The system is also capable of tracking new supply of providers and who does not have access to a primary care provider. Benefits, limitations and risks of the model are discussed.

Towards a Regulatory Framework for Workflow Improvement in Electronic Medical Records.

Physicians have to complete several time-consuming and burnout-inducing tasks in their EMRs for everyday care of patients. Poor workflow design generates increased effort for physicians. In this study, we measure time doctors take to retrieve and review information in the patient chart at the beginning of a visit; one of approximately 12 tasks a doctor must do in the EMR during the visit. Information retrieval takes approximately 40 minutes per day. Automation could save 75% of that time. We estimate that if every family doctor in Canada could save 30 minutes through automation of just this one process, we could free up time equivalent to >3000 physicians and >5 million patients; enough to absorb the vast majority of patients who currently do not have a doctor. We know of no more powerful intervention than workflow automation in Canadian EMRs to increase the supply of doctors while simultaneously reducing a major cause of burnout. We recommend an accelerated research program to identify additional opportunities for workflow automation and a regulatory program to ensure that every physician has access to workflow automation in their EMR.

Towards a Regulatory Framework for Electronic Medical Record Interoperability in Canada.

All complex systems are potentially predisposed to failure. Healthcare systems are complex systems that are prone to many errors that can result in dire consequences for patients and healthcare providers. The healthcare system in Canada is under unprecedented strain due to shortages of healthcare providers, provider burnout, inefficient workflows, and a lack of appropriate digital infrastructure. We used failure mode and effects analysis (FMEA) to identify the failure modes for care provided in primary care settings. We identified failure modes in appointment scheduling, patient-provider communications, referrals, laboratory and diagnostic procedures, and medication prescriptions as the main failure modes. To mitigate the detected risks, we recommend solutions to 'close the loop' on failure modes to prevent patients from falling through the cracks, as vulnerable patients who cannot advocate for themselves are most likely to do so. We provide preliminary requirements for a regulatory regime for electronic health records that can reduce provider burnout, improve regulatory compliance, and improve system efficiency, all while improving patient safety, experience, and outcomes.

Analyzing the expression pattern of the noncoding RNAs (HOTAIR, PVT-1, XIST, H19, and miRNA-34a) in PBMC samples of patients with COVID-19, according to the disease severity in Iran during 2022-2023: A cross-sectional study.

Background and aims: MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are well-known types of noncoding RNAs (ncRNAs), which have been known as the key regulators of gene expression. They can play critical roles in viral infection by regulating the host immune response and interacting with genes in the viral genome. In this regard, ncRNAs can be employed as biomarkers for viral diseases. The current study aimed to evaluate peripheral blood mononuclear cell (PBMC) ncRNAs (lncRNAs-homeobox C antisense intergenic RNA [HOTAIR], -H19, X-inactive-specific transcript [XIST], plasmacytoma variant translocation 1 [PVT-1], and miR-34a) as diagnostic biomarkers to differentiate severe COVID-19 cases from mild ones. Methods: Candidate ncRNAs were selected according to previous studies and assessed by real-time polymerase chain reaction in the PBMC samples of patients with severe coronavirus disease 2019 (COVID-19) (n = 40), healthy subjects (n = 40), and mild COVID-19 cases (n = 40). Furthermore, the diagnostic value of the selected ncRNAs was assessed by analyzing the receiver-operating characteristic (ROC). Results: The results demonstrated that the expression pattern of the selected ncRNAs was significantly different between the studied groups. The levels of HOTAIR, XIST, and miR-34a were remarkably overexpressed in the severe COVID-19 group in comparison with the mild COVID-19 group, and in return, the PVT-1 levels were lower than in the mild COVID-19 group. Interestingly, the XIST expression level in men with severe COVID-19 was higher compared to women with mild COVID-19. ROC results suggested that HOTAIR and PVT-1 could serve as useful biomarkers for screening mild COVID-19 from severe COVID-19. Conclusions: Overall, different expression patterns of the selected ncRNAs and ROC curve results revealed that these factors can contribute to COVID-19 pathogenicity and can be considered diagnostic markers of COVID-19 severe outcomes.

Characterization of Inclination Analysis for Predicting Onset of Heart Failure from Primary Care Electronic Medical Records.

The aim of this study is to characterize the performance of an inclination analysis for predicting the onset of heart failure (HF) from routinely collected clinical biomarkers extracted from primary care electronic medical records. A balanced dataset of 698 patients (with/without HF), including a minimum of five longitudinal measures of nine biomarkers (body mass index, diastolic and systolic blood pressure, fasting glucose, glycated hemoglobin, low-density and high-density lipoproteins, total cholesterol, and triglycerides) is used. The proposed algorithm achieves an accuracy of 0.89 (sensitivity of 0.89, specificity of 0.90) to predict the inclination of biomarkers (i.e., their trend towards a 'survival' or 'collapse' as defined by an inclination analysis) on a labeled, balanced dataset of 40 patients. Decision trees trained on the predicted inclination of biomarkers have significantly higher recall (0.69 vs. 0.53) and significantly higher negative predictive value (0.60 vs. 0.55) than those trained on the average values computed from the measures of biomarkers available before the onset of the disease, suggesting that an inclination analysis can help identify the onset of HF in the primary care patient population from routinely available clinical data. This exploratory study provides the basis for further investigations of inclination analyses to identify at-risk patients and generate preventive measures (i.e., personalized recommendations to reverse the trend of biomarkers towards collapse).

Association between Epstein-Bar virus and colorectal cancer: A systematic review and meta-analysis.

AIM: This study aimed to investigate the prevalence and any potential association between Epstein-Barr virus (EBV) infection and colorectal cancer (CRC). METHODS: A systematic literature search was performed by finding relevant cross-sectional and case-control studies from main online databases. Heterogeneity, odds ratio (OR), and corresponding 95% confidence interval (CI) were applied to all studies through meta-analysis and forest plots. The analysis was performed using STATA Software v.14.1. RESULTS: Twenty-three articles were included in the meta-analysis, eight of them were case/control and 15 were cross-sectional. The pooled prevalence of EBV among 1954 CRC patients was 18% (95% CI: 12%-26%; I2 = 93.14%). Furthermore, in geographical regions, the highest and lowest prevalence of EBV was observed in South America 30% (95% CI: 18%-43%) and Africa 0% (95% CI: 0%-5%), respectively. An association was found between EBV infection and CRC [OR = 3.4 (95% CI (1.13-10.27); I2 = 72.3%)]. CONCLUSION: EBV infection is associated with CRC and can be considered a potential risk factor for the development of CRC. Although the exact molecular mechanism of EBV infection in the development of CRC is still unknown, it seems that latent infection by EBV, intestinal damage, and inflammation can be important factors in the induction of CRC.

Evaluation of MicroRNA Expression Pattern (miR-28, miR-181a, miR-34a, and miR-31) in Patients with COVID-19 Admitted to ICU and Diabetic COVID-19 Patients.

INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.

Global epidemiology of HBV infection among hemodialysis patients: A systematic review and meta-analysis.

BACKGROUND & AIMS: Hemodialysis (HD) is a life-saving procedure that purifies the blood in patients with end-stage renal disease (ESRD). Among all major complications, blood-borne diseases like hepatitis B virus (HBV) may be exposed as serious side effects of hemodialysis. A comprehensive review of the global burden of HBV among HD patients has not been written so far. The aim of the current systematic review and meta-analysis was to determine the globally epidemiology of HBV infection among HD patients. METHODS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles that investigated the prevalence of HBV among HD patients were searched from the major databases such as EMBASE, PubMed, Web of Science collection, and Scopus. Pooled prevalence with 95% CI and identification of heterogeneity were obtained using the random effects model and Cochran's Q-test, respectively, and quantification was evaluated using the I2 statistics. All statistical analyses were performed by STATA 14.1 statistical software. RESULTS: among 322 datasets (795,623 cases) that included in this study, the pooled prevalence of HBV infection among HD patients was 7.32% (95% CI: 6.53-8.15%; I2 = 97.91%), including 7.57% (95% CI: 6.69-8.48%) for HBsAg and 6.09% (95% CI: 4.05-8.49%) for DNA, respectively. In addition, based on geographic area, the prevalence was 7.44% (95% CI: 6.35-8.61%) in Asia, 4.32% (95% CI: 2.21-7.04%) in North America, 7.07% (95% CI: 6.35-8.61%) in Europe, 5.52% (95% CI: 3.60-7.78%) in Africa, 8.45% (95% CI: 5.81-11.78%) in Oceania, and 9.73% (95% CI: 7.11-12.70%) in South America. CONCLUSIONS: Our analysis indicates a relatively high prevalence of HBV infection in HD patients, even in some developed countries. Considering that ESRD patients are not able to properly respond to the vaccination strategies in order to develop an acceptable immunity, vaccination of healthy individuals is highly recommended to arm their bodies for possible immunocompromise conditions in the future. Moreover, donated blood in blood transfusion centers should be checked for possible hepatitis B virus infection using sensitive molecular tests.

Association between human polyomavirus infection and brain cancer: A systematic review and meta-analysis.

AIM: The aim of this study was to investigate the prevalence and potential association between the infection with some members of the polyomaviridae family of viruses and development of the brain tumors. METHODS: A systematic literature search was performed by finding relevant cross-sectional and case-control studies from a large online database. Heterogeneity, OR, and corresponding 95% CI were applied to all studies by meta-analysis and forest plots. The analysis was performed using Stata Software v.14. RESULTS: Twenty-three articles (33 datasets) were included in the meta-analysis, four (four datasets) of which were case/control studies and the rest were cross-sectional. The pooled prevalence of polyomaviruses among brain cancer patients was 13% (95% CI: 8-20%; I2 = 96.91%). In subgroup analysis, the pooled prevalence of JCV, SV40, BKV and Merkel cell polyomavirus was 20%, 8%, 6%, and 16%, respectively. An association was found between polyomavirus infection and brain cancer [summary OR 7.22 (95% CI (2.36-22.05); I2 = 0%)]. The subgroup analysis, based on the virus type, demonstrated a strong association between JCV infection and brain cancer development [summary OR 10.34 (95% CI 1.10-97.42; I2 = 0%)]. CONCLUSION: The present study showed a significant association between polyomavirus infection and brain tumors. Moreover, these results suggest that polyomavirus infection may be a potential risk factor for the development of brain cancer.

Expression profiling of inflammation-related genes including IFI-16, NOTCH2, CXCL8, THBS1 in COVID-19 patients.

The present study aimed to scrutinize the expression profile of inflammatory-related genes (IFI-16, NOTCH2, CXCL8, and THBS1) from acute to post-acute stage of this infectious epidemic. The current cross-sectional study consisted of 53 acute-phase COVID-19 patients and 53 healthy individuals between February and March 2021. The extraction of total RNA was performed from PBMC specimens and also expression level of selected genes (IFI-16, NOTCH2, CXCL8, and THBS1) was evaluated by real-time PCR. Subsequently, levels of these factors were re-measured six weeks after the acute phase to determine if the levels of chosen genes returned to normal after the acute phase of COVID-19. Receiver operating characteristic (ROC) curve was plotted to test potential of genes as a diagnostic biomarker. The expression levels of inflammatory-related genes were significantly different between healthy and COVID-19 subjects. Besides, a significant higher CXCL8 level was found in the acute-phase COVID-19 compared to post-acute-phase infection which may be able to be considered as a potential biomarker for distinguishing between the acute phases from the post-acute-phase status. Deregulation of the inflammatory-related genes in COVID-19 patients, especially CXCL-8, can be serving as potent biomarkers to manage the COVID-19 infection.

An annoying enteric virus: A systematic review and meta-analysis of human astroviruses and gastrointestinal complications in children.

Human astroviruses (HAstVs) have frequently been detected in individuals with acute gastroenteritis (AGE). However, a precise estimate of the overall prevalence of the virus in children with AGE as well as the possible association of the virus with gastrointestinal complications is not available up to now. The present study estimated the overall prevalence of HAstVs in children with gastrointestinal complications as well as the association between the virus and symptoms. We systematically searched four international databases (PubMed, Scopus, Web of Science, and Google scholar) to find studies on the prevalence of HAstVs in people with AGE published between Jan 2000 and Sep 2021. Analysis of the 223 included studies presented a 4.2% (95% CI 3.8%-4.8%) prevalence of the virus in AGE individuals. Based on case-control studies, a significant association between these viruses and AGE was detected (OR: 2.059, 95% CI; 1.438-2.949). HAstV-1 and HAstV-VA-2 is the most and least common genotypes in the AGE patients, respectively (59.0%, 95% CI: 52.1%-65.6% vs. 4.9%, 95% CI: 2.6%-9.1%). Due to the statistically significant association between HAstV and gastrointestinal complications, more attention should be paid to these viruses in people with AGE and more studies should employ case-control design.

Biophysical and ultrasonographic changes of acute Old World cutaneous leishmaniasis skin lesions in comparison with uninvolved skin: A possible tool for non-invasive early detection and treatment outcome assessment.

Cutaneous leishmaniasis (CL) is a skin disease caused by intracellular protozoa, which is endemic in Iran. The goal of this study was to compare biophysical characteristics in CL lesions with uninvolved skin. Stratum corneum hydration, transepidermal water loss, surface friction, pH, sebum, melanin, erythema, temperature, elasticity parameters (R0, R2, and R5), thickness and echo-density of epidermis and dermis were measured on the active erythematous indurated part of a typical CL lesion in 20 patients, and compared with the same location on the other side of the body as control. Paired t-test was used for statistical analyses and a p < 0.05 was considered significant. Melanin content, R2 and echo-density of dermis were significantly lower, whereas transepidermal water loss, friction index, pH, erythema index, temperature, and the thickness of dermis were significantly higher in CL lesions. There was no significant difference in stratum corneum hydration, sebum, R0, R5, thickness of epidermis, and density of epidermis between CL and normal skin. CL lesions are characterized by certain changes in biophysical and ultrasonographic properties, which are mostly correlated with histological features. These changes are likely to be useful in the non-invasive early detection of CL and also as treatment outcome measures for clinical trials of new treatment modalities for CL in the future.

Efficacy of intra-lesional injections of meglumine antimoniate once a week vs. twice a week in the treatment of cutaneous leishmaniasis caused by L. tropica in Iran: A randomized controlled clinical trial.

Treatment of Cutaneous leishmaniasis (CL) is based on using antimoniate derivatives; patients' compliance for systemic injections is low due to the pain and systemic complications. In this randomized open trial, the efficacy of intra-lesional (IL) injections of meglumine antimoniate (MA) once a week vs. twice a week in the treatment of Anthrpoponothic CL caused by L. tropica was studied. Eligible volunteer patients were selected according to inclusion/exclusion criteria. The included patients were randomly allocated to receive IL-MA injections once a week or twice a week. The primary outcome was set as complete healing of the lesion(s), and defined as complete re-epithelialization and absence of induration in the lesions. A total of 180 parasitologicaly proven CL patients caused by L. tropica were recruited, 90 patients were treated with weekly IL-MA and 90 patients received IL-MA twice a week. The complete cure was 87.9% vs. 89.2% in the group received weekly and twice a week IL-MA injections, respectively (P = 0.808). Patients' compliance was acceptable and side effects were limited to a few local allergic reactions to MA. Median time to healing was significantly shorter in patients who received IL-MA twice a week (median ± SE) 37±3.8, (CI: 29.6-44.4) days compared to whom received IL-MA once a week 60±2.3, (CI: 55.6-64.5) days (P< 0.001), however the number of injections was higher in group who received IL-MA twice a week (12 vs. 9 injections). In conclusion, the rate of cure in the group of CL patients with IL-MA twice a week was not significantly different from the group who received IL-MA once a week shorten, but the duration of healing was shorter in the group who received IL-MA twice a week while the group received more injections so is recommended to use IL-MA once a week due to the fact the compliance is acceptable with limited side effects. Clinical Trial Registration: IRCT20081130001475N13; https://en.irct.ir/.

Software Architecture for Automated Assessment of Prescription Writing.

Prescribing skills are a crucial competency in medical practice considering the increasing numbers of medications available and the increasingly complex patients with multiple diseases faced in clinical practice. Medical students need to become proficient in these skills during training, as required by medical licensing colleges. Not only is teaching the fundamentals of safe and cost-effective prescribing to medical students challenging but evaluating their prescribing skills by faculty members is difficult and time consuming. The COVID-19 pandemic has accelerated the interest in clinically relevant online exams, including automated assessment of short answer style questions. The goal of this project was to design a software to automate the assessment of learners' prescriptions written during low stakes formative assessments. After establishing the components of a legal prescription with multiple medications, and identifying the sources of errors in prescribing and prescribing assessment, we designed and validated an architecture and developed a prototype for automated parsing of learner prescriptions.

The expression patterns of MALAT-1, NEAT-1, THRIL, and miR-155-5p in the acute to the post-acute phase of COVID-19 disease.

INTRODUCTION: One of the hallmarks of COVID-19 is overwhelming inflammation, which plays a very important role in the pathogenesis of COVID-19. Thus, identification of inflammatory factors that interact with the SARS-CoV-2 can be very important to control and diagnose the severity of COVID-19. The aim of this study was to investigate the expression patterns of inflammation-related non-coding RNAs (ncRNAs) including MALAT-1, NEAT-1, THRIL, and miR-155-5p from the acute phase to the recovery phase of COVID-19. METHODS: Total RNA was extracted from Peripheral Blood Mononuclear Cell (PBMC) samples of 20 patients with acute COVID-19 infection and 20 healthy individuals and the expression levels of MALAT-1, NEAT-1, THRIL, and miR-155-5p were evaluated by real-time PCR assay. Besides, in order to monitor the expression pattern of selected ncRNAs from the acute phase to the recovery phase of COVID-19 disease, the levels of ncRNAs were re-measured 6‒7 weeks after the acute phase. RESULT: The mean expression levels of MALAT-1, THRIL, and miR-155-5p were significantly increased in the acute phase of COVID-19 compared with a healthy control group. In addition, the expression levels of MALAT-1 and THRIL in the post-acute phase of COVID-19 were significantly lower than in the acute phase of COVID-19. According to the ROC curve analysis, these ncRNAs could be considered useful biomarkers for COVID-19 diagnosis and for discriminating between acute and post-acute phase of COVID-19. DISCUSSION: Inflammation-related ncRNAs (MALAT-1, THRIL, and miR-150-5p) can act as hopeful biomarkers for the monitoring and diagnosis of COVID-19 disease.

Human papilloma virus (HPV) and prostate cancer (PCa): The potential role of HPV gene expression and selected cellular MiRNAs in PCa development.

BACKGROUND: Prostate cancer (PCa) is one of the most common and health-threatening cancers in men worldwide. The human papillomavirus (HPV) is considered one of the organisms with the potential to be involved in the progression of this cancer. In the present study, we evaluated the association between the expression levels of HPV genes with the expression of selected cellular miRNAs (miR-19a, miR-21, miR-23b, miR-34a, miR-150-5p, and miR-155) and their targets genes (P53, Rb, c-Myc, TIMP-1, MMP-2, MMP-9, PDCD4, Bcl-2, and Survivin) in PCa tissue samples. METHODS: HPV detection and genotyping were performed on the tissues of 112 PCa patients and 39 healthy individuals. The expression profile of miRNA was evaluated by SYBR Green-based real-time PCR. As well Human Survivin ELISA Kit was utilized to determine the concentrations of Retinoblastoma, P53, survivin, Bcl-2, c-Myc, TIMP-1, MMP-2, MMP-9, and PDCD4 in the prostate tissues. RESULTS: According to our findings, HPV genome was detected in 28.7% (21/73) of PCa tissue specimens and 17.94% (7/39) control samples. There was no significant association between the presence of HPV infection with PCa (OR = 2.01, 95%CI = 0.8-5.68, P = 0.102). We found that mean expression level of miR-19a (3.7 ± 4.3, p-value: 0.0007), and -21 (2.5 ± 2.8, p-value<0.0001) were significantly higher and miR-23b (-2.14 ± 3.08, p-value: 0.003) and -34a (-3.12 ± 3.28, p-value: 0.0001) levels were significantly lower in PCa tissue samples than in control tissue samples. CONCLUSION: Present research indicated that HPV positive PCa has a distinct miRNA profile compared with HPV negative PCa.

Toxicity and Tolerability of 177Lu-DOTA-TATE PRRT with a Modified Administered Activity Protocol in NETs of Variable Origin - A Phase 2 Registry Study.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has been recently approved for advanced, metastatic, or progressive neuroendocrine tumors (NETs). OBJECTIVE: This study reports the adverse events (AEs) observed with patient-tailored administered activity. METHODS: Fifty-two PRRT naive patients were treated with 177Lu-DOTATATE. The administered activity ranges between 2.78 and 5.55 GBq/cycle using the patient's unique characteristics (age, symptoms, blood work, and biomarkers). RESULTS: The protocol was well tolerated with the overwhelming majority of participants being forty- six (88%), completing all 4 induction therapy cycles. The median cumulative administered activity was 19.6 GBq (ranged 3.8-22.3 GBq). A total of 42/52 (81%) reported at least one symptom, and 43/52 (83%) had evidence of biochemical abnormality at enrollment that would meet grade 1 or 2 criteria for AEs. These symptoms only slightly increase with treatment to 50/52 (96%) and 51/52 (98%), respectively. The most common symptoms were mild fatigue (62%), shortness of breath (50%), nausea (44%), abdominal pain (38%), and musculoskeletal pain (37%). The most common biomarker abnormalities were mild anemia (81%), reduced estimated glomerular filtration rate (eGFR) (58%), increased alkaline phosphatase (ALP) (50%), and leukopenia (37%). Of critical importance, no 177Lu-DOTATATE related grade 3 or 4 AEs were observed. CONCLUSION: Tailoring the administered activity of 177Lu-DOTATATE to the individual patient with a variety of NETs is both safe and well-tolerated. No patient developed severe grade 3 or 4 AEs. Most patients exhibit symptoms or biochemical abnormality before treatment and this only slightly worsens following induction therapy.

Salivirus infection: Systematic review and meta-analysis of association with gastrointestinal symptoms in children.

Salivirus (SaV) is a newly described member of the family Picornaviridae that has been associated with gastrointestinal (GI) symptoms, particularly in children. The aim of the present study was to evaluate the prevalence of SaV in symptomatic children and its potential association with GI complications. A systematic search was conducted from 01 December 2009 to 10 December 2020, in three major English databases, including Scopus, PubMed and Web of Science as well as Google scholar search engine. Random effect model-based overall prevalence and odds ratio (OR) were assessed in cross-sectional and case-control studies by STATA 14.1. The random effect model-based pooled prevalence of SaV was 1.6% (95% CI, 0.010-0.022%) and overall OR for all eight case-control studies indicated an association (3.19 with 95% confidence interval 1.35-7.57) that was not statistically significant, due to the small number of studies available. More comprehensive case-control studies in multiple geographies should be conducted on the prevalence of SaV in children.