Proportion Of Abnormalities Research Articles

An In Vivo Platform for Rebuilding Functional Neocortical Tissue.

Recent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types within the grafts, abnormal proportions of cell types, abnormal cytoarchitecture, and inefficient vascularization. Here, we devised a transplant platform for testing neocortical tissue prototypes. Dissociated mouse embryonic telencephalic cells in a liquid scaffold were transplanted into aspiration-lesioned adult mouse cortices. The donor neuronal precursors differentiated into upper and deep layer neurons that exhibited synaptic puncta, projected outside of the graft to appropriate brain areas, became electrophysiologically active within one month post-transplant, and responded to visual stimuli. Interneurons and oligodendrocytes were present at normal densities in grafts. Grafts became fully vascularized by one week post-transplant and vessels in grafts were perfused with blood. With this paradigm, we could also organize cells into layers. Overall, we have provided proof of a concept for an in vivo platform that can be used for developing and testing neocortical-like tissue prototypes.

Analysis of risk variables for association with maxillary sinus mucosal thickenings: a cone-beam computed tomography-based retrospective study

PurposeThis study aimed to determine which patient-related, anatomical, pathologic, or iatrogenic variables may be directly associated with and which may have a modifying effect on the generation of maxillary sinus (MS) mucosal thickenings.MethodsA total of 278 cone-beam computed tomography (CBCT) scans obtained from 114 males and 164 females were evaluated. The protocol included the assessment of 21 candidate variables, of which 18 were bilateral and 3 were unique. The relationship among the study variables and the mucosal thickenings were examined individually and adjusted for confounding using univariate and multivariate binary logistic regression models.ResultsThe prevalence of mucosal thickenings was 71.20% at patient level and 53.40% at sinus level. The ostium height > 28.15 mm, the infundibulum length ≤ 9.55 mm, the infundibulum width ≤ 0.50 mm, along the occurrence of periapical lesions and slight-to-severe periodontal bone loss acted as strong/independent risk variables for MS mucosal thickenings. Confounding and interaction relationships between MS height and depth, and between the alveolar process type and the presence of foreign materials with respect to age stratum > 47.50 years might be also associated with the mucosal thickenings.ConclusionsWhile increased ostium height, decreased infundibulum length/width, the presence of periapical lesions and periodontal involvement might be the foremost indicator variables for MS mucosal thickenings, there are synergistic relationships among the increased sinus height and depth as well as aging regarding atrophic/partially atrophic alveolar process status and the presence of foreign materials that may be also associated with a greater proportion of these mucosal abnormalities.

Electrocardiogram abnormalities and renal impairment in patients with type 2 diabetes mellitus: A healthcare facilities-based cross-sectional study in Dang district of Nepal.

The global burden of diabetes mellitus is rising substantially, with a further increase in cardiovascular and kidney disease burden. These public health problems are highly prevalent in low- and middle-income countries, including Nepal. However, there is limited evidence on cardiac and renal conditions among patients with type 2 diabetes mellitus. We determined the status of electrocardiogram (ECG) abnormalities and renal impairment among patients with type 2 diabetes mellitus in Nepal. We carried out a cross-sectional study in Tulsipur Sub-Metropolitan City of Nepal using a multistage stratified sampling technique to recruit patients with type 2 diabetes mellitus. We used World Health Organization stepwise approach to surveillance (WHO STEPS) questionnaires and carried out resting ECG to collect data of 345 patients with type 2 diabetes mellitus. Logistic regression analysis assessed the factors associated with ECG abnormalities and renal impairment. The study showed that 6.1% of participants had major ECG abnormalities (95% confidence interval [CI] 3.8-8.6%), which were associated with hypertension (P=0.01%) and low socioeconomic status (P=0.01). The proportion of major and/or minor ECG abnormalities was 47.8% (95% CI 40.5-51%), and were significantly associated with age (odds ratio [OR] 1.04, 95% CI 1.01-1.07), higher education (OR 3.50, 95% CI 1.31-9.33), unemployment (OR 3.02, 95% CI 1.08-8.48), body mass index (OR 1.09, 95% CI 1.02-1.17) and duration of type 2 diabetes mellitus >5 years (OR 2.42, 95% CI 1.19-4.93). The proportion of renal impairment was 3.5% (95% CI 1.5-4.5%) which was associated with older age (OR 1.08, 95% CI 1.00-1.17) and hypertension (OR 12.12, 95% CI 1.07-138.22). A significant proportion of patients with type 2 diabetes mellitus had ECG abnormalities and renal impairment, which were significantly associated with hypertension. Therefore, hypertension management and early screening are essential to prevent future cardiorenal complications among patients with type 2 diabetes mellitus.

Microbiota-derived metabolites in colorectal cancer patients in preoperative period.

Short-chain fatty acids (SCFAs) are microbial derived metabolites, which have multiple beneficial properties. The amount of SCFAs depends on several factors, such as age, diet (mainly intake of dietary fiber), and overall health condition. The normal proportion between SCFAs is 3:1:1 for acetate, proprionate and butyrate, respectively. In colorectal cancer (CRC) patients, microbiota alterations have been shown. Consequently, metabolome within the gut might change to a large extent. Therefore, the aim of this study was to analyse the content of SCFAs and the proportion between SCFAs in the stool obtained from CRC patients in preoperative period. This study included 15 patients with CRC in preoperative period. The stool samples were taken and stored at -80°C in the Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Poland. The analysis of SCFAs from stool samples was conducted by means of gas chromatography. This study included mainly males (66.67%, n=10). In all patients, there was abnormal proportion between SCFAs. The extremely higher concentration of butyrate was noted in 2 samples (13.33%) compared to the rest of patients. However, based on normal proportion between SCFAs, the results <1 for butyrate were noted in 93.33% of patients. SCFAs pool is altered in CRC patients, among others characterized by low level of butyrate. It should be considered to administer butyrate supplementation to CRC patients especially prior to surgery to support an appropriate preparation to this treatment.

Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis

BackgroundAlcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. MethodsIn this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. ResultsAs indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1β, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. ConclusionDietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota−gut−brain axis.

Chromosomal abnormalities in fetuses with congenital heart disease: a meta-analysis.

The aim of this meta-analysis was to evaluate the risk of chromosomal abnormalities in fetuses with congenital heart disease (CHD). Four literature databases were searched until 17th January 2022 using the relevant medical subject heading terms, word variants, and keywords for "congenital heart defect, fetal, and chromosomal abnormalities". The prevalence of overall chromosomal abnormality, aneuploidy, 22q11 deletion, other copy number variants (CNVs), and variants of unknown significance (VOUS) was analyzed. 45 studies met the inclusion criteria for the analysis. The pooled proportion of overall chromosomal abnormalities, aneuploidy, 22q11 deletion, and other CNVs in fetuses with CHD was 23% (95% CI: 20-26%), 19% (95% CI, 16-22%), 2% (95% CI, 2-3%), and 4% (95% CI, 3-5%), respectively. The incidence of overall chromosomal abnormalities, aneuploidy, and other CNVs in non-isolated CHD was higher than in isolated CHD, with odds ratios of 3.08, 3.45, and 4.02, respectively. The incidence of overall chromosomal abnormalities in septal defects was higher than in conotruncal defects and other defects, with odds ratios of 1.60 and 3.61, respectively. In addition, the pooled proportion of VOUS in CHD was 4%. CHD is commonly associated with chromosomal abnormalities. If karyotyping or fluorescence in situ hybridization is normal, chromosomal microarray should be performed to look for submicroscopic abnormalities, especially in fetuses with non-isolated CHD and septal defects.

S-29-6: ELECTROCARDIOGRAPHIC ABNORMALITIES AMONG NEWLY PRESENTING HYPERTENSIVE PATIENTS: REPORT FROM CARDIOVASCULAR RISK PREDICTION REGISTRY

Background: Cardiovascular diseases (CVDs) have become a significant public health concern globally. Standard electrocardiography (ECG) remains an essential diagnostic procedure for cardiovascular risk stratification in hypertension. The co-existence of electrocardiographic abnormalities with hypertension is associated with an increased risk of cardiovascular morbidity and mortality. Data showing electrocardiographic abnormalities among newly diagnosed hypertensives in this environment is limited. Objective: To provide the spectrum of ECG abnormalities among newly presenting hypertensive patients seen at the University College Hospital, Ibadan. Design and method: This observational study was conducted using data from the Cardiovascular Risk Prediction (CRP) registry domiciled at University College Hospital (UCH). Data collection spanned from 2019 to 2022. New patients presenting with hypertension at the cardiology clinic were received and assessed, and cardiovascular risk factors were stratified to identify cardiovascular morbidity and mortality indicators. All participants underwent standard 12 lead ECG. Fasting venous blood was collected to assess serum electrolytes, urea, creatinine, and lipid panels. Statistical Analysis was performed using Statistical Package for Social Sciences (SPSS) version 21. Results: Six hundred and twelve participants comprising 49.7% of women with a mean age of 53.66 ± 15.5 years with complete ECG interpretations were analyzed. A third of the participants had Left ventricular hypertrophy (LVH), with one in ten having strain patterns. About 19%, 10.6%, and 1.8% of participants presented with conduction abnormalities, left atrial enlargement (LAE), and atrial fibrillation, respectively. Mean age, blood pressure parameters, and QT/QTc intervals were comparable in both sexes. Compared to women, men had higher mean urea (29.81 ± 14.1 vs 26.45 ± 11.3 mg/dl;p &lt; 0.002) and creatinine (1.21 ± 0.6 vs 0.94 ± 0.4 mg/dl; p &lt; 0.0001)) and greater proportion of conduction abnormalities (22.1% vs 15.9%;p = 0.05), LVH(36.9% vs 27.6%;p = 0.014), LVH plus strain pattern(13.4% vs 7.0%;p = 0.009), and LAE (13.5% vs 0.7%;p = 0.019). Women were heavier with higher mean total cholesterol (191.75 ± 44.5 vs. 179.92 ± 47.9 mg/dl; p &lt; 0.004) and LDL cholesterol (121.83 ± 37.6 vs. 114.35 mg/dl; p = 0.21). Participants with LVH had higher mean Systolic (146.87 ± 24.7 vs142.19 ± 23.1 mmHg; p = 0.023) and diastolic blood pressure (91.15 ± 16.5 vs 85.97 ± 13.4mmHg; &lt; 0.0001),creatinine (1.15 ± 0.7 vs 1.04 ± 0.41 mg/dl; p = 0.017) and QTc interval (483 ± 83.5 vs 463.81 ± 55.6; ms p &lt; 0.007) and coexisted with LAE compared with those without LVH. Conclusion: Left ventricular hypertrophy was the predominant abnormality in the studied population. Abnormal ECG findings were more common in men, and those with LVH had more cardiovascular risk than women. Early identification and management of these risks are essential in preventing cardiovascular morbidity and mortality.

Clinical Features and Differences of Miller Fisher Syndrome in Southern China: Retrospective Analysis of 72 Patients in 13 Provinces of Southern China.

We aimed to determine the clinical features of Miller Fisher syndrome (MFS) in southern China and compare them with those presenting in other countries. We collected the medical records of patients diagnosed with MFS during 2013-2016. We analyzed the age, sex, onset season, precursor events, clinical symptoms and signs, findings of nerve conduction studies (NCS), cerebrospinal fluid (CSF), therapeutic remedies, nadir time, and length of hospital stay of patients with MFS in southern China. We concurrently compared the differences between urban and rural areas and between patients with incomplete ophthalmoplegia (IO) and complete ophthalmoplegia (CO). The study enrolled 72 patients: 36 from rural areas and 36 from urban areas, and 50 males and 22 females. The mean age at onset was 47.72 years, and 30 (41.7%) and 21 (29.2%) patients developed MFS in spring and winter, respectively. The typical triad of ophthalmoplegia, ataxia, and areflexia was observed in 50 (69.4%) patients. A history of upper respiratory tract infection 1 week before onset was found in 52.8% of the patients, while 5.6% experienced gastrointestinal infections and 48 (73.8%) exhibited albuminocytological dissociation in the CSF study. Only 26 (36.1%) patients presented abnormalities in NCS. Moreover, restricted outward eyeball movement presented in 83.5% of the patients with classic MFS and acute ophthalmoplegia, and bilateral symmetrical ophthalmoplegia presented in 64.2%. With the exception of the higher proportion of NCS abnormalities in urban areas (47.2% vs. 25.0%), urban and rural differences were insignificant regarding sex ratio, age at onset, high-incidence season, precursor events, disease characteristics, and albuminocytological dissociation in the CSF. Furthermore, patients with CO were older than those with IO (64.53±7.69 vs. 43.19±14.40 years [mean±standard deviation], p<0.001). The patients with MFS were mostly male and middle-aged, and most presented in winter and (especially) spring. More than half of the patients had clear precursor events, most of which were classic MFS with the typical triad. More than 70% of the patients presented albuminocytological dissociation in the CSF. NCS abnormalities were uncommon in MFS. The age at onset was lower in patients with IO than in patients with CO; bilateral symmetrical extraocular muscle paralysis was the most common symptom, and the external rectus was the most frequently involved muscle.

Assessment of Esophageal Motility in Patients With Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition causing esophageal symptoms, particularly dysphagia. Despite the important progress in the treatment of EoE, a significant proportion of patients continue to report symptoms that negatively impact quality of life. Esophageal manometry is used to assess motility and function, but is not routinely used in EoE. We aimed to systematically review and describe current literature evaluating esophageal manometry in EoE. Forty-eight studies meeting the criteria were identified, describing 802 patients. Using standard water swallow protocols, the proportion of abnormalities detected was not dissimilar to other populations, apart from disorders of esophago-gastric outflow, which were found in 5%. Twelve studies described pretreatment and posttreatment manometry, with motility normalization after pharmacological therapy reported in 20%. Early, brief panesophageal pressurization was described in a number of studies and was more prevalent in the few studies utilizing additional provocation testing. Reports in the literature regarding temporal relationships between manometric findings and symptoms are variable. Esophageal manometry may be capable of detecting clinically relevant changes to esophageal function in EoE. Possible mechanisms are altered neuromuscular function because of secretory products of EoE and/or fibroinflammatory processes, manifesting as pressurization because of altered esophageal compliance. Some changes may be reversible with therapy. Drawing strong conclusions from the literature is difficult, with bias toward case reports and retrospective observation. Adaptations to assessment protocols to include provocation testing may provide more robust evaluation and detect clinically relevant, subtle changes in esophageal function, earlier within the patient pathway.

Osmotic characteristics of water retention structures of Bursera microphylla in relation to soil salinity

With a worldwide increase in soil salinity, as well as the climate crisis raising global temperatures, it is important to understand the effects of soil salinity on plant survival. One way to understand how plants may evolve to survive in these xeric desert environments is to gain a further understanding of existing halophytic (live in saline environments) and/or xerophytic (live in dry, arid environments) plants. Bursera microphylla in particular is quite interesting because it is both a halophyte and a xerophyte. One reason it is able to survive in dry environments is due to its bulbs at the base of the trunk and major limbs of the tree, which have been shown to store water during droughts. To facilitate mineral uptake, plants use ATP to transport NaCl ions into the plant, which facilitates water uptake. Because observed field conditions in the Baja California Peninsula were extremely xeric, most plants there have distinct evolutionary traits to facilitate water storage or retention. The Elephant Tree (Bursera microphylla) gets its name from the abnormal proportions of the base of its stem, which is much wider than much of the tree, and studies show that this disproportionately wide stem can store water for use during times of drought, which are common in the Baja California Peninsula. Our hypothesis was that sodium chloride was taken up through the plant’s root structure to facilitate this water transportation, and that this sodium chloride accumulation was directly proportional to the soil salinity. We tested this hypothesis via light microscopy of plant tissues to observe cell tonicity under different concentrations of saline solution. soil salinity was measured using saturated extraction. The results of this experiment show that most cells within the “bulb” structures were isotonic at a concentration approximately twice as high as that of root tissue and ambient soil salinity, therefore supporting the presented hypothesis.

Figure Types, Challenges of Making Garments and Implication for Nigerian Women and Garment Makers

The shapes of ladies with uneven shapes can be classified in many different ways with some presenting figure issues. There is a significant correlation of various figure types with garment making, which means that there are certain types of clothing that need to be left out and others that need to be selected in relation to the individual's figure type. When it comes to the making of clothing according to figure types, some of the key concerns are balancing, proportioning, and ensuring that the clothing fits correctly on the body, along with the issue of how the garment appears. In the paper, it is stated that Nigerian garment makers are confronted with the problem of the inability to handle necessary alterations in order to correct the figure faults of people with abnormal body proportions due to the lack of basic patterns for constructing garments.

Single-cell profiling of the microenvironment in decidual tissue from women with missed abortions

To define the decidual microenvironment in euploid and aneuploid missed abortions and elective termination of pregnancies. Prospective, multicenter, observational study. Tertiary hospital and descriptive analysis of transcriptomic data. A total of 34 patients experienced abortions, including 6 women who underwent elective terminations of pregnancy of unplanned pregnancies and 28 cases with missed abortions. All patients underwent their operations from Sep, 2021 to Sep,2022. All women underwent villous copy number variation sequencing. Meanwhile, single-cell RNA sequencing were performed in the decidual tissues of 16 women, and reverse transcription quantitative polymerase chain reaction were performed in the decidual tissues of 18 women. Single-cell RNA sequencing was used to explore the changes in the microenvironment of decidual tissues in abortions. Single-cell RNA sequencing indicated that the microenvironment of the decidual tissue of the missed-abortion group was altered, and that the stromal cells (SCs), natural killer cells, macrophages, and epithelial cells all reflected functional imbalances compared with the elective terminations of pregnancy group. We also noted a correlation between the proportion of senescent SCs and chromosomal abnormalities in missed-abortion embryos. The proportion of senescent decidual SCs in the decidual tissue of missed-abortion patients with common chromosomal abnormalities of the fetus was higher, and this was not conducive to fetal growth and was closely related to missed abortion. In addition, we ascertained that the strength of the HLA-KIR interaction between NK1 and NK2 subsets and non-senescent stromal cell subsets in the missed abortion decidual tissues was weakened, potentially playing a role in the occurrence of missed abortion. The decidualization of SCs in the missed-abortion decidual tissues was impaired, the clearance of senescent SCs by NK cells was weakened, the killing toxicity of non-senescent SCs was enhanced, macrophages were insufficiently resident at the maternal-fetal interface, and epithelial cell differentiation was unbalanced-all creating a maternal microenvironment that was not conducive to fetal growth. We posit that interfering with the expression of dysregulated genes in the missed-abortion decidual tissues and reversing the maternal microenvironment might constitute an effective means toward improving the clinical outcome of missed abortions. Intriguingly, we observed a correlation between stromal cell senescence and embryonic chromosomal abnormalities. Thus, we hypothesize that the DIO2 marker of senescent SCs can be used as a risk indicator for the occurrence of missed miscarriages with chromosomal abnormalities of the embryos, and that it can be applied to guide the clinical diagnosis and treatment of recurrent abortion. NCT04425317.

Real-time detection of abnormal driving behavior based on long short-term memory network and regression residuals

Abnormal driving behavior is one of the main causes of roadway collisions. In most studies of abnormal driving behavior, the abnormal driving status is detected and analyzed using classification algorithms directly or using unsupervised learning algorithms to classify reconstruction or prediction residuals. However, abnormal driving behavior data are difficult to acquire and label. Also, a class imbalance issue is inherent in the algorithm training process due to the relatively sparse data for abnormal driving behavior. Moreover, current studies that include residual analysis tend to focus on individual points and thus fail to capture the continuity characteristic of abnormal driving behavior.To address these problems, a long short-term memory-residual (LSTM-R) algorithm is proposed to detect abnormal driving behavior in real time. The proposed algorithm (referred to simply as LSTM-R) has two steps. First, an LSTM network is used to fit the current vehicle kinematic data based on historical data to obtain the root mean square residual at each moment. Second, a time window-based residual algorithm is designed and employed to detect abnormal driving behavior according to the magnitude and continuity of the residuals. To verify the effectiveness of LSTM-R, an experimental test was conducted in Nanjing, China. The vehicle kinematic data were collected non-intrusively using a smartphone.In addition, AdaCost, SMOTEBoost, EasyEnsemble, LightGBM-residual, and linear regression-residual algorithms were employed for comparison with the proposed algorithm to assess its effectiveness. The effects of (1) the degree-of-fit of the LSTM network, (2) the LSTM-R parameters, and (3) the abnormal driving behavior percentage on the detection results were analyzed in detail. First, both the underfitting and overfitting of the LSTM network compromise the detection performance. Second, within a certain range of values, the LSTM-R parameters have little effect on the detection results. Third, the detection results are affected only slightly by the abnormal proportion. The results show that LSTM-R, with a maximum F1-score of 0.866, significantly outperforms the other five algorithms. Furthermore, even if only 10% abnormal driving behavior is in the training set, LSTM-R’s F1-score can still be close to 0.86, indicating a significant relaxation of the requirements for labeled data. Also, the required data are easy to collect, which indicates LSTM-R’s extensive application possibilities. This paper thus provides an effective method for the real-time detection of abnormal driving behavior and also supports driving risk assessment and driving behavior improvement with the overall goal to enhance roadway safety.

An Exponentially Weighted Moving Average Procedure for Detecting Back Random Responding Behavior

AbstractBack random responding (BRR) behavior is one of the commonly observed careless response behaviors. Accurately detecting BRR behavior can improve test validities. Yu and Cheng (2019) showed that the change point analysis (CPA) procedure based on weighted residual (CPA‐WR) performed well in detecting BRR. Compared with the CPA procedure, the exponentially weighted moving average (EWMA) obtains more detailed information. This study equipped the weighted residual statistic with EWMA, and proposed the EWMA‐WR method to detect BRR. To make the critical values adaptive to the ability levels, this study proposed the Monte Carlo simulation with ability stratification (MC‐stratification) method for calculating critical values. Compared to the original Monte Carlo simulation (MC) method, the newly proposed MC‐stratification method generated a larger number of satisfactory results. The performances of CPA‐WR and EWMA‐WR were evaluated under different conditions that varied in the test lengths, abnormal proportions, critical values and smoothing constants used in the EWMA‐WR method. The results showed that EWMA‐WR was more powerful than CPA‐WR in detecting BRR. Moreover, an empirical study was conducted to illustrate the utility of EWMA‐WR for detecting BRR.

HPV-negative high-grade cervical precancerous lesions or invasive cancer in China: A post hoc analysis of a multicentric clinical study.

To evaluate HPV-negative cervical high-grade precancerous lesions or cancer in China. Histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were searched in a multicentric clinical study. All patients underwent cobas HPV testing, liquid-based cytology, DNA ploidy analysis, and colposcopy-guided biopsy. According to clinical practice, patients underwent p16ink4a staining and cone biopsy. Comparisons were made between HPV-negative and -positive patients for clinical characteristics. The study found 61 cases of cobas HPV-negative CIN2+ among 797 cases of histologically confirmed CIN2+, including 38 CIN2, 20 CIN3, and 3 invasive cancers. The prevalence of HPV-negative CIN2+ and CIN3+ was 7.7% (95% confidence interval [CI] 5.8-9.5) and 5.7% (95% CI 3.5-8.0), respectively. Among 24 cases with p16 staining, 20 showed p16 positivity. The proportions of normal or minor abnormalities in terms of colposcopy, cytology, and DNA ploidy were higher in HPV-negative cases than in HPV-positive cases. When adding cytology to the screening of symptomatic or previously HPV-positive women, the prevalence of HPV-negative CIN2+ or CIN3 would decrease by approximately 50%. Less than one-tenth of CIN2+ are missed by HPV-only screening, and they have smaller lesions than HPV-positive cases. Colposcopy should be considered for symptomatic or previously HPV-positive women with HPV-negative results.

Clinical features of chronic hepatitis B patients with lean nonalcoholic fatty liver disease.

The clinical features have been well described in obese chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). However, little is known about the clinical features of lean CHB-NAFLD patients. The study retrospectively included treatment-naïve CHB patients who underwent ultrasound between 2015 and 2021. Liver fibrosis was assessed by aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis-4 score (FIB-4), NAFLD fibrosis score (NFS), and transient elastography. Among 1226 CHB-NAFLD patients, 25.0% patients were lean. The age, gender, and platelet, alanine aminotransferase, AST, and albumin levels were comparable between lean CHB-NAFLD and nonlean patients. The levels of plasma glucose, triglycerides, total cholesterol, and uric acid, as well as proportions of concurrent hypertension and diabetes, were lower in lean patients. Lean patients presented higher hepatitis B surface antigen (HBsAg) levels (3.4 log10 IU/ml vs. 3.2 log10 IU/ml, p=0.006), hepatitis B virus (HBV) DNA levels (4.1 log10 IU/ml vs. 3.2 log10 IU/ml, p<0.001), and hepatitis B e antigen (HBeAg) positive proportions (40.4% vs. 30.2%, p=0.002) than nonlean patients. The values of APRI, FIB-4, and liver stiffness were comparable between two groups. However, lean patients had lower NFS values (-3.0 vs. -2.6, p<0.001) and lower proportions (12.6% vs. 21.1%, p=0.003) of advanced fibrosis (NFS≥-1.5) than nonlean patients. Similar results were observed in HBeAg-positive and HBeAg-negative subgroups. Nearly a quarter of CHB-NAFLD patients were lean. Lean patients had lower proportions of metabolic abnormalities and advanced liver fibrosis than nonlean patients. However, lean CHB-NAFLD patients had higher HBsAg levels, HBV DNA levels, and HBeAg-positive proportions. Registry and registration no. of the study/trial: Clinicaltrials.gov, Identifier: NCT03097952.

R-DA-Edoch/R-DHAP Alteration Could Overcome High Risk Factors in Younger Mantle Cell Lymphoma

Background: Mantle-cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma, with a median overall survival of only 3~5 years in the era of immunochemotherapy. Although first-line intensive chemotherapy with rituximab (R) and high dose cytarabine combined with autologous transplantation (ASCT) has significantly prolonged the survival of patients with MCL, some patients still die within few years. Our published data show that Chinese patients with MCL are younger and have a higher proportion of TP53 deletion and MYC abnormality [Oncotarget, 2015 Dec 8;6(39):42362-71]. Considering the efficacy and tolerability of the dose-enhanced immunochemotherapy R-DA-EDOCH regimen in patients with multiple high-risk aggressive B-cell lymphomas and the potential higher proliferative activity of tumor cells in Chinese patients, we conducted a prospective clinical study of alternate R-DA-EDOCH/R-DHAP induction therapy for young patients with newly-diagnosed MCL (NCT02858804). Here, we analyzed the efficacy and safety of this regimen. Methods: The main inclusion criteria for patients with newly-diagnosed MCL included age ≤ 65 years, Ann Arbor stage II~IV and ECOG ≤ 1. During induction, patients received alternate R-DA-EDOCH/R-DHAP for two cycles. Patients who achieved less than partial remission would quit the trial, while the other patients would continue another one cycle of treatment. After finishing the 3 cycles of inductive treatment, patients would decide whether to continue ASCT consolidation therapy or another cycle of consolidation. R maintenance therapy was recommended to all patients. The primary endpoint of this study was the progression-free survival (PFS). Key secondary endpoints were complete response rate (CRR) and objective response rate (ORR) at the end of induction (EOI), overall survival (OS), minimal residual disease (MRD) status and the incidence of adverse events (AEs). Results: In this study, we recruited 55 patients with a median age of 53 years (range, 37~65 years) and a male/female ratio of 2.2:1. Totally, 61.8% of patients were of at least one risk factor (HR) according to risk stratification, pathological classification and molecular genetic abnormalities. All patients received at least two cycles of alternate R-DA-EDOCH/R-DHAP immunochemotherapy, and one patient dropped out due to the poor response. The ORR of the alternate R-DA-EDOCH/R-DHAP inductive treatment was 98% (95% CI 90-100), and the CRR was 89% (95%CI 78-96). There was no significant difference in CRR and ORR among patients with different prognostic characteristics. Moreover, patients rapidly achieved MRD-negative and the rate of MRD-negative after 2 cycles of treatment, the end of the inductive therapy and the end of the overall treatment was 79.2%, 88.7% and 90.6%, respectively. The median follow-up of the cohort was 31 months (range 4-86). The 3-year PFS and OS rates were 66.3% and 85.4%, respectively. Sequential ASCT consolidation and/or R maintenance slightly increased CRR but significantly prolonged PFS of patients (3-year PFS rate: ASCT+R 90.4% versus R 64.6% versus without ASCT/R 33.3%, P<0.001). There was no significance difference in PFS and OS between patients with (n=34) and without (n=9) HR (PFS P=0.537, OS P=0.408). For patients receiving ASCT and R maintenance, OS was even longer in patients with HR (mOS not reach versus 47m, P=0.007). Univariate analysis showed that age≥60 years, blastoid/pleomorphic pathologic morphology and TP53 double-allele events were still the risk factors for PFS in this therapeutic pattern. However, high tumor proliferative activity (such as Ki-67≥30% and MYC abnormality) and specific genetic abnormalities (such as 17p deletion, 9p deletion, etc) showed no significant adverse prognostic influence. In particular, patients who achieved MRD-negative by treatment had longer PFS (P<0.001). The alternate R-DA-EDOCH/R-DHAP regimen was well tolerated, and no patients were discontinued due to intolerance of treatment-related AEs. AEs were mainly hematologic and at least one hematologic AEs occurred in 85.5% of the patients. Grade 3-4 leukopenia and neutropenia were found in 49.1% and 58.2% of the patients, respectively. Conclusion: The alternate R-DA-EDOCH/R-DHAP induction therapy showed great efficacy and tolerability in young patients with newly diagnosed MCL and could overcome the adverse prognostic impact of some high-risk factors. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Safety, Feasibility, and Efficacy of Upfront Daratumumab-Based Therapy in Blacks with Dysproteinemia

Background: Black patients (pts) with dysproteinemia are underrepresented in clinical trials included in new drug applications and biological license application submissions. Even after approval, access to novel therapies remains a challenge. Daratumumab (dara) is an anti-CD38 monoclonal antibody, which has revolutionized the care of patients with both multiple myeloma (MM) and light chain (AL) amyloidosis. The underrepresentation of black pts in clinical trials of dara in newly diagnosed patients with dysproteinemia raises concerns regarding the safety, tolerability and efficacy of dara in this population. We report the results from a cohort of pts treated with dara in the management of newly diagnosed MM (NDMM) and AL amyloidosis. Methods: The Cancer and Aging Resilience Evaluation in Hematologic Malignancies (CARE-Heme) registry is an ongoing prospective registry enrolling pts ≥50 years of age with a diagnosis of hematologic malignancy undergoing treatment at a single institution. For this analysis, we included pts with NDMM and AL amyloidosis treated with dara-based combination therapy between January 2020 and January 2022. We obtained baseline disease- and patient-related characteristics. Toxicity was evaluated by chart review up to the first 6 cycles and adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events (CTCAE v5.0). For patients receiving >1 cycle, response assessment was ascertained using International Myeloma Working Group (IMWG) uniform response criteria. All patients were followed until progression, death or last follow up and progression-free survival (PFS) and overall survival (OS) were measured using Kaplan Meier methods. Health-related quality of life (HRQoL) was measured using Patient-Reported Outcomes Measurement Information System (PROMIS) global 10 and quantified using physical health (PH) and mental health (MH) t-scores at baseline and 3 month follow up. Variables were compared in each race by using independent and paired sample t-tests as appropriate. Results: Over the study period, 36 black pts (NDMM=32; AL=4) and 50 white pts (NDMM=44; AL=6) received upfront dara-based combination therapy. There were no differences in age or sex, IGH translocations, but there was a higher incidence of cytogenetic high-risk disease among the black pts in our cohort (p=0.02). Black pts presented with more advanced disease at the time of presentation - hypercalcemia 33% vs. 14%, p=0.04; renal dysfunction 56% vs. 28%, p=0.01; anemia 67% vs. 38%, p=0.01). Incidence of bone disease was similar between the groups (p=0.69) (Table 1) Among blacks, the most utilized regimen was DaraVRd (56%), DaraRd (17%), DaraKRd (11%) and DaraVCd (11%). While for the white pts, it was DaraVRd (52%), DaraRd (12%), DaraKRd (8%) and DaraVCd (22%). Blacks had a similar incidence of ≥grade 3 non-hematologic AEs (p=0.21), with fatigue, diarrhea and leg edema being the most common. There is a trend towards higher ≥grade 3 hematologic AEs which did not reach statistical significance (p=0.05). After 6 cycles of therapy, overall response rate was comparable (100% vs. 94%, p=0.81) among the two groups (≥VGPR 47% vs. 62%, p=0.36). With 18 month median follow up, there was no difference in median PFS and OS, both not reached (Figure 1). Complete quality of life (QoL) t-scores were available at baseline for 55 pts (20 blacks and 35 whites). The baseline PH and MH related QoL scores were comparable between whites and blacks (p= 0.51; p=0.58, respectively). From baseline to 3 months follow up, PH t-scores improved in both whites as well as blacks although the difference was not statistically significant. Meanwhile, MH t-scores remained largely unchanged from baseline to follow up in both groups. Conclusions: We report the largest cohort to date of black pts with dysproteinemia systematically treated with frontline dara. Our data shows the feasibility of this strategy in a single institution setting with comparable safety, efficacy and HRQoL with the use of upfront dara-based combinations in black and white pts. Our data supports comparable clinical outcomes among black pts when treated with novel therapeutic combinations despite a higher proportion of high risk cytogenetic abnormalities in our cohort without an increase in AEs. Minority representation in cancer clinical trials as well as access to approved novel therapies can significantly help mitigate disparities in outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Morphological analysis of the impact of diabetes on gingival capillaries with non-invasive blood flow scope – A preliminary study

Background/purposeDiabetes mellitus (DM) induces microangiopathy in various tissues, leading to several complications. However, limited studies have reported the impact of diabetes on gingival capillaries. The aim of this study was to investigate the morphological evaluation and to analyze the influence of diabetes on gingival capillaries. Materials and methodsMedical interviews and periodontal examinations were performed on 29 patients with periodontitis. The subjects were divided into two groups: those with or without type 2 diabetes (DM or non-DM group). Gingival capillary density and morphology in the buccal marginal gingiva were evaluated using a capillary blood flow scope (magnification: × 560). ResultsProbing pocket depth, plaque index, and gingival index were not significantly different between the DM and non-DM groups. The mean HbA1c was 7.9 ± 1.5% in the DM group (n = 14). Using an oral moisturizing gel as immersion agent, gingival capillaries can be observed under high magnification. The gingival capillary density was 10.5 ± 3.9/mm2 and 9.1 ± 2.7/mm2 in the non-DM group and DM group, respectively. There were no significant differences between the groups. Gingival capillary density was not significantly associated with probing pocket depth, plaque index, or gingival index. The proportion of capillary morphological abnormalities was significantly higher in the DM group than non-DM group. However, capillary morphological abnormalities were not significantly associated with the HbA1c. ConclusionThe present study first documented the morphological abnormalities of gingival capillaries in patients with type 2 diabetes using the capillary blood flow scope. Gingival capillary density might not be affected by diabetes.

Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.

Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.