Comparative evaluation of mucin and total protein in periodontal disease before and after nonsurgical periodontal therapy.

Background: Periodontal ailments cause a quantum leap in the biomarker profile of the saliva. This profile is, in fact, the epiphany of the scale and extent of the disease. Both gingivitis and periodontitis are chronic inflammatory diseases with a step-grade progression. The study aimed to determine the response of the host in these conditions by analyzing concentrations of salivary mucin and total protein activity, before and after nonsurgical periodontal therapy (NSPT). Materials and Methods: Sixty adult subjects were clinically examined and divided into three groups (n = 20) according to the clinical assessment and categorized as Group I (healthy), Group II (gingivitis), and Group III (chronic periodontitis). Whole saliva was collected, and salivary mucin and total protein levels were quantitatively measured at baseline in all the groups and additionally after NSPT in Groups II and III. Results: Levels of mucin and total protein increased in patients with gingivitis and periodontitis. There was a slight decline in mucin levels in periodontitis patients in comparison with the gingivitis group. A positive correlation was found between the respective clinical parameters of both the groups along with their levels of salivary mucin and total protein. It indicated that the response of salivary glands to increase their protective potential caused the change among the groups. Conclusion: Periodontal diseases induce an increase in the levels of mucins and proteins, which is believed as the action of the salivary glands to protect the oral cavity and put off the chaos caused by the microorganisms.

Investigation of Thiol/Disulfide Homeostasis and Clinical Parameters in Rosacea Patients According to Skin Subtypes.

Background/Objective: The aim of this study was to compare thiol/disulfide homeostasis and clinical parameters of rosacea patients across skin subtypes of the disease and healthy controls. Methods: This prospective study included 90 rosacea patients with different skin subtypes (phymatous, erythematotelangiectatic and papulopustular) and ocular involvement and 30 healthy controls. Plasma native thiol (NT), total thiol (TT) and disulfide levels of the patients and controls were measured using an automated spectrophotometric method, and disulfide/native thiol ratio (DNTR), disulfide/total thiol ratio (DTTR) and native thiol/total thiol ratio (NTTR) were calculated. Tear breakup time (TBUT), meiboscore, Schirmer, ocular surface disease index (OSDI) and rosacea-specific quality of life scale (RosaQoL) were measured clinically. Results: Disulfide, DNTR and DTTR were significantly higher, and NT, TT and NTTR were significantly lower in the rosacea patients compared to the controls (p < 0.001). TBUT and Schirmer were significantly lower, and meiboscore and OSDI were significantly higher in the patients compared to the controls (p < 0.01). According to the skin subtypes, disulfide, DNTR and DTTR were significantly higher, and NTTR was significantly lower in the erythematotelangiectatic subtype compared to the other subtypes (p < 0.002). TBUT was significantly lower, and RosaQol was significantly higher in the erythematotelangiectatic subtype (p < 0.0083). Strong correlations were found between DNTR and TBUT and between DNTR and Meiboscore in all subtypes (p < 0.005), while there were strong correlations between DNTR and OSDI and between DNTR and RosaQol only in the erythematotelangiectatic and papulopustular subtypes (p < 0.05). Conclusions: The thiol/disulfide homeostasis shifted towards disulfides, an indicator of oxidative stress in rosacea, and this was more pronounced in the erythematotelangiectatic subtype. The impairment in TBUT and RosaQol was also more prominent in the erythematotelangiectatic subtype and strongly associated with the DNTR.

Epidemiological, clinical, biological and evolutionary profile of scorpion envenomed children under one year to 15 years in the Souss Massa region of Morocco.

Morocco is one of the main countries affected in North African with the scorpion envenomations. Faced with the threat, significant morbidity and a major risk of death especially in children, a detailed identification of scorpionic profile of stings remains important for health authorities at national or even regional level. The current study aims to establish the epidemiological, clinical, biological and evolutionary data of the scorpionism by analyzing 383 cases of scorpion stings in children from three age groups (<1 year, 1-5 years and >5 years), admitted at the Regional Hospital Hassan II-Agadir in the Souss Massa region during the period of 9 years and 10 months from January 2013 to October 2022. Our results showed that patients under 1 year of age presented the most severe cases and had the highest mortality rate. However, the clinical signs and symptoms observed illustrated severe damages to vital systems, particularly the cardiovascular, neurological and pulmonary systems, although the signs associated with the latter were present only in cases admitted in grades 2 and 3 for the three age categories studied. Fluctuations in vital constants (temperature and peripheral oxygen saturation, blood pressure, heart rate and respiratory rate), biochemical parameters (ASAT, ALAT, urea and blood creatine, as well as blood sugar) and CBC results revealed major functional disturbances in vital organs, especially in envenomated cases admitted in grade 3. A positive correlation was mentioned between the state of evolution and the various epidemiological parameters, digestive symptoms, as well as signs and symptoms linked to hemodynamic state, general and neurological state. The main interest is to illustrate the seriousness of scorpion envenomations, especially in the high-risk population, for whom an improved therapeutic approach in health centers will undoubtedly be reinforced, and the admission of immunotherapy, as a fundamental part of the treatment, remains important.

The Use of Statins as an Adjunctive Periodontal Disease Treatment: Systematic Review and Meta-Analysis.

BACKGROUND: the purpose of this systematic review was to assess the clinical and radiographic effect of subgingival-administered statins as an adjunct periodontal treatment in patients with periodontitis. METHODS: Electronic literature searches in Medline/PubMed and the Cochrane Library were conducted to identify all relevant articles. Eligibility was based on inclusion criteria which included Randomized Controlled Trials (RCTs) published after 2010, where the periodontal variables were assessed before and after periodontal treatment in combination with a statin administration. The risk of bias was assessed with the ROBINS-2 tool. The outcome variables were probing depth, clinical attachment level, bleeding on probing, and bone fill in systematically healthy patients, patients with type 2 diabetes, and smokers. RESULTS: Out of 119 potentially eligible articles, 18 randomized controlled trials were included with a total of 1171 participants. The data retrieved from the meta-analysis showed the positive effect that statins have as an adjunctive periodontal disease treatment. When comparing the different types of statins, the PD reduction in the Simvastatin group was significantly higher than the Atorvastatin group at 6 months and at 9 months, while no differences between statins were found for the rest of the outcomes. Over 66% of the articles presented an overall risk of bias with some concerns, making this a limitation of this present RCT. CONCLUSIONS: The adjunct administration of statins has proven to have a positive effect on the periodontium by improving both clinical and radiographic parameters by a considerable margin.

Association of Clinicopathological Factors With MMP13 (rs2252070) Gene Polymorphism in Swedish Patients With Colorectal Cancer.

BACKGROUND/AIM: Matrix metalloproteinase 13 (MMP13) has been reported to be involved in tumor development and progression, including of colorectal cancer (CRC). This study aimed at evaluating whether the MMP13 rs2252070 gene polymorphism is associated with clinicopathological factors and its influence on long-term survival in Swedish patients with CRC. PATIENTS AND METHODS: A total of 723 patients with CRC were genotyped using TaqMan single nucleotide polymorphism assays based on polymerase chain reaction. RESULTS: Assessing clinicopathological factors, we demonstrated that having the G/G genotype for MMP13 rs2252070 was significantly associated with poor differentiation, higher serum level of carcinoembryonic antigen and higher lymph node status. Moreover, the presence of a G allele was significantly related to larger tumor size in rectal cancer but had a significantly protective role against mucinous cancer, perineural invasion and lymphovascular invasion. Kaplan-Meier analysis showed no difference between genotypes regarding cancer-specific survival. CONCLUSION: Our findings highlight the potential of MMP13 rs2252070 polymorphism as a useful predictor of poor differentiation, serum level of carcinoembryonic antigen, lymph node status, tumor size, mucinous cancer, perineural invasion and lymphovascular invasion in patients with CRC.

Exploring the Microbiome Landscape of Dental Plaque: A Cross-Sectional Analysis in Periodontal Health and Disease.

OBJECTIVE: This study aimed to comprehensively analyze the microbiome of dental plaque in individuals with varying periodontal statuses, encompassing both periodontal health and disease. The primary objectives were to identify microbial markers associated with different clinical conditions, explore variations in microbial diversity, and investigate potential correlations between the oral microbiome and clinical parameters. METHODS: A cross-sectional design was employed, involving 164 participants aged 18 to 65 years. Inclusion criteria comprised individuals with good oral and systemic health for the periodontal health group and those diagnosed with various stages of periodontal disease for the periodontal disease group. Dental plaque samples were meticulously collected from diverse tooth surfaces, and clinical examinations were conducted to assess periodontal health status. High-throughput sequencing of the 16S ribosomal RNA (rRNA) gene was utilized for microbiome analysis. RESULTS: Demographic characteristics revealed a balanced distribution between the periodontal health and disease groups. Clinical parameters, including probing depth, clinical attachment loss, and bleeding on probing, exhibited significant differences between the two groups (p < 0.001). Microbial diversity indices indicated a higher diversity in the periodontal health group compared to the disease group (p < 0.001). Analysis of relative abundance of bacterial phyla identified significant variations, with Firmicutes, Bacteroidetes, and Actinobacteria showing differential prevalence between health and disease (p < 0.05). Differentially abundant taxa analysis highlighted specific species associated with each clinical condition, including Prevotella intermedia and Porphyromonas gingivalis. Network analysis revealed complex microbial interactions within the oral microbiome. Functional predictions indicated variations in metabolic capabilities between health and disease, with potential implications for virulence and antibiotic resistance. CONCLUSION: This study provides a comprehensive analysis of the oral microbiome in periodontal health and disease, revealing significant associations between microbial composition and clinical parameters. The identification of microbial markers and functional insights enhances our understanding of the complex interplay within the oral ecosystem. These findings hold promise for advancing diagnostic and therapeutic approaches tailored to individual microbial profiles.

Utility of clinical and MR imaging parameters for prediction and monitoring of response to capecitabine and temozolomide (CAPTEM) therapy in patients with liver metastases of neuroendocrine tumors.

BACKGROUND: This study explores the predictive and monitoring capabilities of clinical and multiparametric MR parameters in assessing capecitabine and temozolomide (CAPTEM) therapy response in patients with neuroendocrine tumors (NET). PATIENTS AND METHODS: This retrospective study (n = 44) assessed CAPTEM therapy response in neuroendocrine liver metastases (NELM) patients. Among 33 monitored patients, as a subgroup of the overall study cohort, pretherapeutic and follow-up MRI data (size, apparent diffusion coefficient [ADC] values, and signal intensities), along with clinical parameters (chromogranin A [CgA] and Ki-67%), were analyzed. Progression-free survival (PFS) served as the reference. Responders were defined as those with PFS ≥ 6 months. RESULTS: Most patients were male (75%) and had G2 tumors (76%) with a pancreatic origin (84%). Median PFS was 5.7 months; Overall Survival (OS) was 25 months. Non-responders (NR) had higher Ki-67 in primary tumors (16.5 vs. 10%, p = 0.01) and increased hepatic burden (20% vs. 5%, p = 0.007). NR showed elevated CgA post-treatment, while responders (R) exhibited a mild decrease. ADC changes differed significantly between groups, with NR having decreased ADCmin (-23%) and liver-adjusted ADCmean/ADCmean liver (-16%), compared to R's increases of ADCmin (50%) and ADCmean/ADCmean liver (30%). Receiver operating characteristic (ROC) analysis identified the highest area under the curve (AUC) (0.76) for a single parameter for ∆ ADC mean/liver ADCmean, with a cut-off of < 6.9 (76% sensitivity, 75% specificity). Combining ∆ Size NELM and ∆ ADCmin achieved the best balance (88% sensitivity, 60% specificity) outperforming ∆ Size NELM alone (69% sensitivity, 65% specificity). Kaplan-Meier analysis indicated significantly longer PFS for ∆ ADCmean/ADCmean liver < 6.9 (p = 0.024) and ∆ Size NELM > 0% + ∆ ADCmin < -2.9% (p = 0.021). CONCLUSIONS: Survival analysis emphasizes the need for adapted response criteria, involving combined evaluation of CgA, ADC values, and tumor size for monitoring CAPTEM response in hepatic metastasized NETs.

Assessing the Impact of Smoking Cessation Interventions on Periodontal Health and Gingival Inflammation in Smokers with Periodontitis.

Background: Smoking is a well-established risk factor for periodontitis, a chronic inflammatory disease of the oral cavity. While smoking cessation has been linked to improved overall health, its specific impact on periodontal health and gingival inflammation in individuals with periodontitis remains less explored. Materials and Methods: We conducted a prospective cohort study involving 200 smokers diagnosed with periodontitis. Participants were divided into two groups: Group A received comprehensive smoking cessation interventions, including counseling and pharmacotherapy, while group B continued smoking without intervention. Periodontal health was assessed through clinical parameters, including probing depth (PD) and clinical attachment level (CAL), at baseline and 6 months post intervention. Gingival inflammation was evaluated using the Gingival Index (GI). Results: After 6 months, group A exhibited a significant reduction in mean PD (from 4.5 mm to 3.2 mm) and CAL (from 5.0 mm to 3.5 mm) compared to group B. Conversely, group B showed no significant change in these parameters. The GI score significantly decreased in group A (from 2.8 to 1.2) but remained unchanged in group B. Furthermore, group A demonstrated a higher rate of smoking cessation (72%) compared to group B (14%). Conclusion: Smoking cessation interventions play a crucial role in improving periodontal health and reducing gingival inflammation in smokers with periodontitis. The observed reductions in PD, CAL, and gingival inflammation highlight the potential benefits of smoking cessation on oral health outcomes in this high-risk population.

Comparing the Effectiveness of Traditional Periodontal Surgery Versus Non-Surgical Therapy: A Randomized Controlled Trial.

Background: Periodontal disease, characterized by inflammation and infection of the supporting structures of teeth, poses a significant oral health challenge. Traditional periodontal surgery and non-surgical therapy, such as scaling and root planing, are established treatment approaches for addressing periodontal disease. Materials and Methods: The study enrolled 120 adult patients diagnosed with moderate to severe periodontal disease. Participants were randomly allocated to one of two groups: the traditional surgery group (TSG) or the non-surgical therapy group (NSTG). In the TSG, patients underwent traditional periodontal surgery, which included flap surgery and grafts when deemed necessary. The surgical procedures were performed by experienced periodontal surgeons. In contrast, the NSTG received non-surgical therapy in the form of scaling and root planing administered by trained dental hygienists. Outcome measures encompassed clinical parameters and patient-centered outcomes. Periodontal pocket depth and clinical attachment level, both measured in millimeters, were assessed at baseline, 3 months, and 6 months. Patient-reported outcomes, including pain, discomfort, and satisfaction, were collected through standardized questionnaires at each follow-up visit. Results: Patients in the TSG experienced a notable reduction in pocket depth from a baseline of 6.8 mm to 3.7 mm at the 6-month mark, resulting in a change of -3.1 mm. Conversely, the NSTG exhibited a reduction from 6.7 mm to 4.0 mm, with a change of -2.7 mm. In the TSG, the baseline attachment level of 7.2 mm decreased to 5.1 mm at 6 months, indicating a change of -2.1 mm. In the NSTG, the attachment level decreased from 7.1 mm to 5.5 mm, resulting in a change of -1.6 mm. Patients in the TSG reported an average pain score of 3.6 on a 1-10 scale, discomfort of 4.2, and satisfaction of 7.8. In contrast, patients in the NSTG reported lower pain (2.1) and discomfort (2.9) scores but similar satisfaction levels (8.4). Conclusion: In this randomized controlled trial (RCT), both traditional periodontal surgery and non-surgical therapy demonstrated improvements in clinical parameters and patient-reported outcomes. Traditional surgery resulted in greater reductions in periodontal pocket depth and clinical attachment loss at the 6-month follow-up.

The Effect of a Low-Carbohydrate Diet on Periodontal Health and Inflammation in Patients with Type 2 Diabetes.

Background: The interaction between type 2 diabetes and periodontal disease underscores the importance of exploring dietary interventions that could mitigate inflammation and improve periodontal health in diabetic patients. Materials and Methods: This randomized controlled trial included 100 patients with type 2 diabetes who were equally divided into two groups: Group A (low-carbohydrate diet) and Group B (control group). Patients in Group A followed a low-carbohydrate diet for 12 weeks, while Group B maintained their regular dietary habits. Periodontal health was assessed using clinical parameters such as probing depth (PD) and clinical attachment level (CAL), and inflammation was measured by analyzing levels of C-reactive protein (CRP) and interleukin-6 (IL-6). Statistical analyses were performed using appropriate tests. Results: After 12 weeks, Group A exhibited significant improvements in periodontal health compared to Group B. The mean PD reduction was 0.5 mm in Group A and 0.1 mm in Group B, with a corresponding mean CAL gain of 0.3 mm in Group A and no significant change in Group B. Inflammatory markers also showed favorable outcomes in Group A, with a decrease of 1.2 mg/L in CRP levels and 20% reduction in IL-6 levels. In contrast, Group B demonstrated minimal changes in inflammatory markers. The differences in PD, CAL, CRP, and IL-6 levels between the two groups were statistically significant (P < 0.05). Conclusion: The adoption of a low-carbohydrate diet for 12 weeks demonstrated significant improvements in periodontal health and reduction of inflammation in patients with type 2 diabetes.

Health-Related Quality of Life in Sudanese Children with Nephrotic Syndrome: A Comparative Cross-Sectional Study.

Background: Nephrotic syndrome (NS) is an essential chronic disease in children that has a major impact on a child's health-related quality of life (HRQoL). This study aimed to evaluate the HRQoL of Sudanese children with NS and clinical parameters that can influence their HRQoL. Methods: This study was a descriptive cross-sectional of children with NS conducted in Khartoum state hospitals. A standardized PedsQLTM 4.0 Scale Score evaluated the HRQoL of the participants. Patients' socio-demographics, clinical data, and disease complications were collected using a data collection sheet. This study assessed the HRQoL of children with NS and compared it with apparent age and sex-matched to three groups (healthy children, children with chronic diseases, and kidney-transplanted children). Results: 80 children with NS were recruited from April to August 2021. Children over eight years old represented (63.8%) of the study subjects. The total mean HRQoL scores of nephrotic children were significantly lower than those of healthy children (78.46 ± 24.01) (p = 0.001) and those with other chronic diseases (78.45 ± 24.01) (p= 0.006); however, it was not significantly different from those with kidney transplantation. Socio-demographics did not significantly affect the total mean HRQoL scores of children with NS. Clinical parameters such as the duration of illness, "less than one year" (p= 0.006), and the minimum change nephropathy histopathology (p= 0.035) significantly lowered the total mean HRQoL scores of NS children. Regression analysis further confirmed that edema, proteinuria, and hospital admission had a high impact on the total mean HRQoL. Conclusion: The total mean HRQoL scores of children with NS were low and significantly lower than healthy children. Parameters such as the patient's socio-demographics and phenotype of NS had no significant effect on the total mean HRQoL scores of children with NS. However, other clinical parameters significantly lowered their total mean HRQoL scores.

Screening and staging of chronic obstructive pulmonary disease with deep learning based on chest X-ray images and clinical parameters.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is underdiagnosed with the current gold standard measure pulmonary function test (PFT). A more sensitive and simple option for early detection and severity evaluation of COPD could benefit practitioners and patients. METHODS: In this multicenter retrospective study, frontal chest X-ray (CXR) images and related clinical information of 1055 participants were collected and processed. Different deep learning algorithms and transfer learning models were trained to classify COPD based on clinical data and CXR images from 666 subjects, and validated in internal test set based on 284 participants. External test including 105 participants was also performed to verify the generalization ability of the learning algorithms in diagnosing COPD. Meanwhile, the model was further used to evaluate disease severity of COPD by predicting different grads. RESULTS: The Ensemble model showed an AUC of 0.969 in distinguishing COPD by simultaneously extracting fusion features of clinical parameters and CXR images in internal test, better than models that used clinical parameters (AUC = 0.963) or images (AUC = 0.946) only. For the external test set, the AUC slightly declined to 0.934 in predicting COPD based on clinical parameters and CXR images. When applying the Ensemble model to determine disease severity of COPD, the AUC reached 0.894 for three-classification and 0.852 for five-classification respectively. CONCLUSION: The present study used DL algorithms to screen COPD and predict disease severity based on CXR imaging and clinical parameters. The models showed good performance and the approach might be an effective case-finding tool with low radiation dose for COPD diagnosis and staging.

Essential trace element levels in multiple sclerosis: Bridging demographic and clinical gaps, assessing the need for supplementation.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disorder intricately linked to perturbations in trace element levels. While previous studies have explored circulating trace elements in a limited sample, understanding the impact of demographic and clinical variables on the elemental profile within a larger cohort remains elusive. METHODS: This study aimed to evaluate essential trace elements (Cr, Mn, Co, Cu, Zn, and Se) in the sera of 215 MS patients compared to a meticulously matched control group of 100 individuals with similar gender and age. Our main objective was to identify potential variations in elemental profiles based on demographic and clinical parameters among MS patients, elucidating the prospective relevance of supplementing specific essential trace elements. RESULTS: Data indicated a significant decrease in serum levels of Mn, Co, Zn, and Se, and an increase in Cr in MS patients compared to controls. These trace elements not only discriminated between MS patients and controls but also exhibited distinctive capabilities among demographic subgroups. Gender, smoking habits, and age strata (20-40 years and 41-60 years) revealed discernible variations in elemental profiles between MS patients and their control counterparts. Se demonstrated the singular ability to stratify cases of extreme MS severity, mild relapsing-remitting MS (RRMS) and highly severe secondary progressive MS (SPMS). In contrast, Co significantly differentiated RRMS from primary progressive MS (PPMS), while Cu significantly differentiated SPMS from PPMS. Additionally, Cu showed a negative correlation with MSSS, while Mn and Zn showed a positive correlation with EDSS. CONCLUSION: These findings underscore a substantive deficiency in Mn, Co, Zn, and Se in the MS cohort, supporting targeted supplementation with these trace elements. This study provides a comprehensive understanding of the intricate relationship between essential trace elements and MS, paving the way for further research into personalized nutritional interventions for this complex neurological disorder.

Dose-response association of diabetic kidney disease with routine clinical parameters in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on DKD onset in patients with type 2 diabetes mellitus (T2DM) remains uncertain. Methods: In this systematic review and meta-analysis, we searched multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Library, for studies published from each database inception until January 11, 2024. We included cohort studies examining the association between DKD onset and various clinical parameters, including body mass index (BMI), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and serum uric acid (UA). Random-effect dose-response meta-analyses utilizing one-stage and/or cubic spline models, were used to estimate correlation strength. This study is registered in PROSPERO (CRD42022326148). Findings: This analysis of 46 studies involving 317,502 patients found that in patients with T2DM, the risk of DKD onset increased by 3% per 1 kg/m2 increase in BMI (relative risk (RR) = 1.03, confidence interval (CI) [1.01-1.04], I2 = 70.07%; GRADE, moderate); a 12% increased risk of DKD onset for every 1% increase in HbA1c (RR = 1.12, CI [1.07-1.17], I2 = 94.94%; GRADE, moderate); a 6% increased risk of DKD onset for every 5 mmHg increase in SBP (RR = 1.06. CI [1.03-1.09], I2 = 85.41%; GRADE, moderate); a 2% increased risk of DKD onset per 10 mg/dL increase in TG (RR = 1.02, CI [1.01-1.03], I2 = 78.45%; GRADE, low); an 6% decreased risk of DKD onset per 10 mg/dL increase in HDL (RR = 0.94, CI [0.92-0.96], I2 = 0.33%; GRADE, high), and a 11% increased risk for each 1 mg/dL increase in UA (RR = 1.11, CI [1.05-1.17], I2 = 79.46%; GRADE, moderate). Subgroup analysis revealed a likely higher risk association of clinical parameters (BMI, HbA1c, LDL, and UA) in patients with T2DM for less than 10 years. Interpretation: BMI, HbA1c, SBP, TG, HDL and UA are potential predictors of DKD onset in patients with T2DM. Given high heterogeneity between included studies, our findings should be interpreted with caution, but they suggest monitoring of these clinical parameters to identify individuals who may be at risk of developing DKD. Funding: Shenzhen Science and Innovation Fund, the Hong Kong Research Grants Council, and the HKU Seed Funds, and Scientific and technological innovation project of China Academy of Chinese Medical Sciences.

Paradoxical and Unmasking HIV Immune Reconstitution Inflammation Syndrome in Antiretroviral-Naïve Pregnant Women: A Prospective Cohort Study.

BACKGROUND AND AIMS: Following antiretroviral therapy (ART) initiation, HIV-associated immune reconstitution inflammatory syndrome (IRIS), indicated by an array of opportunistic infections, may occur, presenting as either paradoxical, a worsening of a previously treated infection, or unmasking, a flare-up of an underlying, previously undiagnosed infection. The impact of ART as the backbone of HIV treatment and prevention has prolonged the survival of people living with HIV. In pregnancy, benefits have been shown by slowing HIV progression and preventing perinatal transmission; however, there have been risks of adverse reactions with ART, including immune responses to both the fetus and mother. This study sought to estimate the incidence of HIV-IRIS cumulatively and by type either paradoxical or unmasking IRIS, determine the baseline maternal and HIV clinical markers as predictors of, and analyze the log-rank test for survival time to IRIS outcome assessed by relying on an increase in CD4 count and/or a rapid decrease in viral load. METHODS: An active records study was conducted between June 2019 and March 2020 among ART-naïve pregnant women attending the antenatal care units (ANCu) at the Kenyatta National and Mbagathi Hospitals, Nairobi, Kenya. Participants were aged between 20 and 49 years and had a confirmed HIV-positive test. To ascertain a true case of IRIS, the diagnosis was adjudicated for accuracy and consistency by an independent review committee. Plasma HIV viral load, CD4 counts, and routine laboratory evaluations (hemoglobin, white blood cell count (WBC)) were performed by each hospital's clinical laboratory. The IRIS incidence was assessed using the International Network for Studies Against HIV-Associated IRIS (INSHI) during the first three months after ART initiation. Multivariate Cox regression with IRIS as the outcome, using the SPSSSurvival package, examined the relationship between baseline maternal characteristics and HIV clinical markers before ART initiation and IRIS, and finally, decision-tree analysis for predicting IRIS was performed. RESULTS: From a pool of 532 ART-naïve pregnant women, 133 (25%) developed IRIS, and 97 (72.9%) were in the unmasking category. The accumulated risk of experiencing IRIS symptoms increased from week two (hazard ratio (HR)=0.0287) to week 12 (HR=3.6158). Participants with a maternal BMI (MBMI) of 25-29.9 kg/m2 at baseline were at a higher risk of unmasking IRIS (HR=2.478; P=0.010). The WHO-HIV clinical stages 1 and 2 skewed towards paradoxical IRIS (regression coefficients =-0.111 and -0.276 (P<0.05)), while stage 4 skewed towards unmasking IRIS (regression coefficient=0.047, HR=1.048, P=0.941). A CD4 count > 500 cells/mm^3 skewed towards unmasking IRIS (regression coefficient=0.192, HR=1.211, P=0.416), while RNA-HIV viral loads >50 copies/ml towards paradoxical IRIS (regression coefficient=-0.199, HR=0.820, P=0.360. On decision tree analysis, 85% (P=0.001) of ART-naïve pregnant women with a baseline CD4 count below 500 copies/mm^3 presented with unmasking IRIS. CONCLUSION: For ART-naïve pregnant women, unmasking IRIS is the most common type, and an MBMI of 25-29.9 kg/m2, advanced HIV infection, a CD4 count <500 cells/mm^3, and a higher parity at baseline may be clinically useful predictors. The higher proportion of ART-naïve pregnant women experiencing unmasking as compared to paradoxical IRIS supports the need for earlier assessment based on potential predictors.

Can serum ferritin serve as a biomarker for the prognosis of gynecological malignant tumors? A retrospective cohort study.

PURPOSE: It is widely accepted that there is a strong relationship between iron levels and cancer. This study aimed to investigate the relationship between serum ferritin levels and the severity and prognosis of gynecological malignant tumors. METHODS: This retrospective study included patients with gynecological malignant tumors at Sir Run Run Shaw Hospital in the Department of Obstetrics and Gynecology from January 2013 to June 2019. Patients were grouped according to their serum ferritin level: low (< 13 µg/L), normal (13-150 µg/L), and high (> 150 µg/L). Correlation analyses were performed between serum ferritin level and other factors. Cox univariable and multivariable analysis and Kaplan-Meier survival curves were used to assess the impact of ferritin on survival in patients with gynecologic tumors. RESULTS: The 402 total patients were divided into a low (n= 37), normal (n= 182), and high (n= 183) ferritin level group. Correlation analyses were performed that WBC, MCV, CRP, CA125, and CA153 were significantly positively correlated with serum ferritin level. The Kaplan-Meier survival curves revealed that of the three groups analyzed, the high serum ferritin level group had a significantly shorter survival time versus the normal and low serum ferritin level groups (log-rank P= 0.003). Univariable Cox regression analysis identified that patients with high serum ferritin levels had a significant correlation with risk of death compared to the patients with lower and normal serum ferritin levels. Serum ferritin was not found to be significant (HR = 0.792, 95% CI: 0.351-1.787, P= 0.574) in the multivariable Cox analysis. CONCLUSION: Although this study did not find serum ferritin to be a significant independent prognosis indicator in gynecological malignant tumors, this study did identify that gynecological malignant tumor patients with high serum ferritin levels have significantly less survival time than patients with low or normal serum ferritin levels.

Serum TNF-α level and probing depth as a combined indicator for peri-implant disease

Peri-implant disease (PID) is a general term for inflammatory diseases of soft and hard tissues that occur around implants, including peri-implant mucositis and peri-implantitis. Cytokines are a class of small molecule proteins, which have various functions such as regulating innate immunity, adaptive immunity, and repairing damaged tissues. In order to explore the characteristics and clinical significance of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and tumor growth factor (TGF)-β1 expression levels in serum of patients with peri-implant disease, 31 patients with PID and 31 patients without PID were enrolled. The modified plaque index (mPLI), modified sulcus bleeding index (mSBI), and peri-implant probing depth (PD) were recorded. The levels of serum TNF-α, IL-6, IL-10, and TGF-β1 were detected by ELISA. TNF-α, mPLI, mSBI, and PD levels were significantly higher in the PID group. TGF-β1 levels were significantly higher in the control group. There was a significant positive correlation between TNF-α and mPLI, mSBI, and PD. TGF-β1 was negatively associated with TNF-α, mPLI, mSBI, and PD. Multiple logistic regression analysis showed that TNF-α and PD were risk factors for the severity of PID. The receiver operating curve analysis showed that high TNF-α levels (cut-off value of 140 pg/mL) and greater PD values (cut-off value of 4 mm) were good predictors of PID severity with an area under the curve of 0.922. These results indicated that TNF-α and PD can be used as a biological indicator for diagnosing the occurrence and progression of PID.

Prediction of locally advanced bladder tumor using preoperative clinical parameters.

Background: Staging of bladder cancer (BC) still remains a challenge. In conjunction with imaging, there is a critical need for accessible and cost-effective predictors to evaluate the existence of locally advanced disease. Objective: Our aim was to determine the role of preoperative clinical parameters in predicting locally advanced cT3/4 and/or cN+ in BC. Materials and Methods: Single-center data consisting of 32 patients were collected prospectively and eligible for the final analysis. The demographics data, presence of hydronephrosis, and results of renal function test (blood urea nitrogen [BUN] and serum creatinine [SCr]) were analyzed between the groups. Analysis of the receiver-operating characteristics curve was performed to determine the optimal cutoff value, sensitivity, and specificity of the preoperative clinical parameters, whereas multivariate logistic regression was used to assess the predictive analysis. Results: According to preoperative computed tomography imaging, 17 (53.1%) out of 32 patients with BC had locally advanced disease. Preoperative hydronephrosis and renal insufficiency as indicated by BUN and SCr levels were independently associated with the presence of locally advanced disease (P < 0.05). Multivariate analysis confirmed that the presence of preoperative hydronephrosis and higher level of BUN and SCr were the independent predictors of locally advanced BC (Odds ratio [OR] =6.6; 95% confidence interval [CI]: 1.40-31.05; P = 0.017; OR = 6.6; 95% CI: 1.40-31.05; P = 0.017; OR = 18.67; 95% CI: 3.16-110.29; P = 0.001, respectively). No further variables were statistically significant. Conclusion: Preoperative assessment of hydronephrosis and renal insufficiency was able to predict locally advanced stage risk of BC cT3/4 and/or cN+; thus, preoperative staging might be improved. However, further studies are required to corroborate these findings.

Comparative analysis of monocyte-derived dendritic cell phenotype and T cell stimulatory function in patients with acute-on-chronic liver failure with different clinical parameters.

Background: Acute-on-Chronic Liver Failure (ACLF) patients experience systemic inflammation as well as immune dysfunction and exhaustion. The phenotype and functionality of monocyte-derived dendritic cells in ACLF patients with different clinical parameters have not been elucidated. Methods: This study included 37 cases of ACLF, 20 cases of Chronic Hepatitis B (CHB) patients, and 12 healthy controls. Demographic and laboratory parameters were collected from the enrolled patients. Peripheral blood samples were obtained from the participants. Monocyte-derived dendritic cells were induced and cultured, followed by co-culturing with T cells from the patients. Cell surface markers and intracellular markers were analyzed using flow cytometry. The relationship between these markers and clinical parameters was compared. Results: Our study found that ACLF patients had lower expression levels of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells compared to both CHB patients and healthy controls. IL-4, GM-CSF, and alcohol were found to promote the expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. In ACLF patients, higher levels of procalcitonin (PCT), lower levels of albumin, decreased prothrombin activity and deceased patients were associated with lower expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. Peripheral blood mononuclear cells (PBMCs), after removing adherent cells, were co-cultured with monocyte-derived DC. Our study revealed that patients with infection and low albumin levels exhibited a decreased proportion of T cell subsets within PBMCs. Additionally, these patients' T cells showed lower levels of Ki-67 and interferon-gamma (IFN-γ) production. Conclusion: ACLF patients exhibit varying clinical states, with differences in the phenotype and the ability of monocyte-derived dendritic cells to stimulate T cells. Alcohol can stimulate the maturation of monocyte-derived dendritic cells.

Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity.

Introduction: Dengue virus (DENV) is a flavivirus that has emerged as a global health threat, characterized by either asymptomatic or mild self-limiting febrile illness, but a subset of DENV outbreaks have been associated with severe disease. Studies have looked into the host immune response and dengue viral load during infection. However, it remains unknown how the active microbial isolates modulate the dengue viral infection. In this study, we demonstrate the significance of in-depth analysis of microbiota composition in the serum samples of dengue-infected patients. Materials and methods: RNA was extracted from the serum samples collected from 24 dengue positive patients. The human mapped reads generated through RNA-Sequencing (RNA-Seq) were removed, while the unmapped (non-human) reads were employed for microbial taxonomic classification using Kraken2 and Bracken2. Further, we assessed the initial blood parameters analyzing the complete blood count (CBC) profile of the patients. Results: Findings revealed differential abundance of commensals and pathogenic microbes in the early febrile period of hospitalized dengue patients, segregated into, High Viral Reads (HVR) and Low Viral Reads (LVR). The Campylobacter genus was abundant in the HVR whereas Lactobacillus dominated the LVR patients. At species level, the microbiota of HVR exhibited higher abundance of unique potential opportunistic microbes, compared to the commensal microbes' enrichment in the LVR patients'. We hypothesize that the DENV might alter the microbiota composition as observed by the increase in preponderance of opportunistic pathogens and an absence of commensals in the HVR. The presence of commensals in the LVR might explain, i) overall lower dengue viral reads compared to the HVR, and ii) shift in lymphocytes (high) and neutrophils (low) counts; resulting in a comparatively milder clinical manifestation in this group. Our findings may help in understanding the co-infection aspect that will be important to develop dengue therapeutics and vaccines. Discussion: This study highlights the potential of the unexplored roles of the TAMs in modulating the dengue disease severity using the metatranscriptomic sequencing. This study serves to enhance our understanding of the distinctive microbial and hematologic signatures in the early infection stage that differentiate patients with high viral reads patients from those with low dengue viral reads.