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Long-term follow-up of patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation after primary induction failure

Blood Cancer J. 2023 Dec 10;13(1):179. doi: 10.1038/s41408-023-00953-0.

ABSTRACT

Primary induction failure (PIF) in acute myeloid leukemia (AML) patients is associated with poor outcome, with allogeneic hematopoietic stem cell transplantation (HCT) being the sole curative therapeutic option. Here, we retrospectively evaluated long-term outcomes of 220 AML patients undergoing allogeneic HCT after PIF who never achieved remission, and identified clinical and molecular risk factors associated with treatment response and ultimate prognosis. In this high-risk population, disease-free survival was 25.2% after 5 years and 18.7% after 10 years, while overall survival rates were 29.8% and 21.6% after 5 and 10 years of HCT, respectively. 10-year non-relapse mortality was 32.5%, and 48.8% of patients showed disease relapse within 10 years after allogeneic HCT. Adverse molecular risk features determined at initial diagnosis, poor performance status at the time of allogeneic HCT, and long diagnosis-to-HCT intervals were associated with unfavorable prognosis. Collectively, our data suggests that immediate allogeneic HCT after PIF offers long-term survival and cure in a substantial subset of cases and that high-risk AML patients who never achieved complete response during induction might benefit from early donor search.

PMID:38071327 | DOI:10.1038/s41408-023-00953-0

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Awareness of undergraduate dental students, interns, and freshly graduated dentists about oral manifestation associated with COVID-19

BMC Oral Health. 2023 Dec 9;23(1):990. doi: 10.1186/s12903-023-03666-9.

ABSTRACT

OBJECTIVE: There is growing evidence supporting the presence of oral manifestations associated with COVID-19. The study investigates the knowledge of dental undergraduates and recently graduated dentists concerning oral presentations related to COVID-19.

METHODS: A cross-sectional descriptive study in Saudi Arabia comprised 305 individuals, including undergraduate dental students, interns, and freshly graduated dentists. Data were collected using a questionnaire disseminated to approximately 500 subjects via WhatsApp groups and other applications. The questionnaire was tested in a pilot study for validity, edited, and validated by 2 supervisors at the College of Dentistry, Qassim University, Buraydah, Saudi Arabia. The questionnaire consisted of questions regarding sociodemographic attributes, the level of expertise of dental practitioners, and their knowledge and perspectives regarding COVID-19 and the implementation of oral lesions interrelated to it. The data was subjected to analysis through the utilization of descriptive statistics and chi-square tests, employing the statistical software SPSS (version 24).

RESULTS: About 43.9% of subjects stated that COVID-19 causes oral symptoms. Respondents most frequently reported COVID-19-related dry mouth. Oral ulcers, Candida infection, Hyperpigmentation, tongue coating, atrophy, Petechiae, Herpes, white lesions, Gingivitis, and Periodontitis are further symptoms. COVID-19’s oral manifestation was unknown to 41.0% of subjects, and 37.7% of respondents lacked knowledge regarding the most impacted locations of oral manifestations. Oral signs and COVID-19 symptoms are debated and significantly associated with higher educational levels.

CONCLUSION: The dental students and freshly graduated dentists in this study have proper knowledge of COVID-19 and its symptoms. Also, most dental students and newly graduated dentists recognize the potential correlation between COVID-19 and oral manifestations with an average to excellent knowledge of the types and sites commonly affected. The level of awareness was associated with higher educational levels.

PMID:38071326 | DOI:10.1186/s12903-023-03666-9

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Gamma-glutamyl transferase and calculus of kidney incidence: a Mendelian randomization study

Sci Rep. 2023 Dec 9;13(1):21821. doi: 10.1038/s41598-023-48610-7.

ABSTRACT

Elevated Gamma-glutamyl transferase (GGT) levels are often suggestive of cholelithiasis, and previous studies have indicated that GGT is highly expressed in the urinary system. Therefore, we hypothesized that there may be an association between GGT levels and calculus of kidney (CK) incidence. To investigate this potential causal relationship, we employed Mendelian randomization (MR) analysis. Additionally, we analyzed the levels of other liver enzymes, including alanine transaminase (ALT) and alkaline phosphatase (ALP). The relationship between GGT levels and CK incidence was analyzed using two-sample Mendelian randomization. Summary Genome-Wide Association Studies data were utilized for this analysis. 33 single nucleotide polymorphisms known to be associated with GGT levels were employed as instrumental variables. We employed several MR methods including IVW (inverse variance weighting), MR-Egger, weighted median, weighted mode, and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier). Furthermore, we conducted tests for horizontal multivariate validity, heterogeneity, and performed leave-one-out analysis to ensure the stability of the results. Overall, several MR methods yielded statistically significant results with a p-value < 0.05. The results from the IVW analysis yielded an odds ratio (OR) of 1.0062 with a 95% confidence interval (CI) of 1.0016-1.0109 (p = 0.0077). Additional MR methods provided supplementary results: MR-Egger (OR 1.0167, 95% CI 1.0070-1.0266, p = 0.0040); weighted median (OR 1.0058, 95% CI 1.0002-1.0115, p = 0.0423); and weighted mode (OR 1.0083, 95% CI 1.0020-1.0146, p- = 0.0188). Sensitivity analyses did not reveal heterogeneity or outliers. Although potential horizontal pleiotropy emerged, we speculate that this could be attributed to inadequate test efficacy. However, subsequent use of MR-PRESSO did not provide evidence of pleiotropy. Our analysis suggests a positive association between elevated GGT levels and CK incidence, indicating an increased risk of CK development. However, no causal relationship was observed between levels of ALP or ALT and CK incidence.

PMID:38071316 | DOI:10.1038/s41598-023-48610-7

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Dental pulp cells cocultured with macrophages aggravate the inflammatory conditions stimulated by LPS

BMC Oral Health. 2023 Dec 9;23(1):991. doi: 10.1186/s12903-023-03625-4.

ABSTRACT

BACKGROUND: Pulp inflammation is complex interactions between different types of cells and cytokines. To mimic the interactions of different types of cells in inflamed dental pulp tissues, dental pulp cells (DPCs) were cocultured with different ratios of macrophages (THP-1) or LPS treatment.

METHODS: DPCs were cocultured with various ratios of THP-1, then photographed cell morphology and determined cell viability by MTT assay at preset times. Total RNA was also extracted to measure the inflammation marker-IL-6 and IL-8 expressions by RT-Q-PCR. The DPCs and THP-1 were treated with 0.01 – 1μg/ml lipopolysaccharide (LPS) and extract RNA at preset times, and detected IL-6 and IL-8 expression. DPCs were cocultured with various ratios of THP-1 with 0.1 μg/mL LPS, and detected IL-6 and IL-8 expression after 24 and 48 h. The data were analyzed by unpaired t-test or Mann-Whitney test. Differences were considered statistically significant when p < 0.05.

RESULTS: THP-1 and DPCs coculture models did not suppress the viability of DPCs and THP-1. Cocultured with various ratios of THP-1 could increase IL-6 and IL-8 expressions of DPCs (p = 0.0056 – p < 0.0001). The expressions of IL-6 and IL-8 were stronger in higher ratio groups (p = 0.0062 – p < 0.0001). LPS treatment also induced IL-6 and IL-8 expressions of DPCs and THP-1 (p = 0.0179 – p < 0.0001 and p = 0.0189 – p < 0.0001, separately). Under the presence of 0.1 μg/mL LPS, DPCs cocultured with THP-1 for 24 h also enhanced IL-6 and IL-8 expression (p = 0.0022). After cocultured with a higher ratio of THP-1 for 48 h, IL-6 and IL-8 expressions were even stronger in the presence of LPS (p = 0.0260).

CONCLUSIONS: Coculturing dental pulp cells and macrophages under LPS treatment aggravate the inflammatory process. The responses of our models were more severe than traditional inflamed dental models and better represented what happened in the real dental pulp. Utilizing our models to explore the repair and regeneration in endodontics will be future goals.

PMID:38071305 | DOI:10.1186/s12903-023-03625-4

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Comparative effectiveness and cost evaluation of Risankizumab and Adalimumab in the management of psoriasis: a real-world study in Saudi Arabia

Cost Eff Resour Alloc. 2023 Dec 9;21(1):95. doi: 10.1186/s12962-023-00504-1.

ABSTRACT

BACKGROUND: Psoriasis, an immune-mediated chronic inflammatory disease primarily affecting skin and joints, has varying prevalence rates globally. It manifests in five types, with chronic plaque psoriasis being the most common. Treatment, which has no definitive cure, aims for complete resolution of skin symptoms and depends on disease extent, severity, and impact on patients’ lives. Biologics are an emerging treatment for psoriasis, targeting specific inflammatory pathways for potentially safer, more effective outcomes. However, these come with significant costs, necessitating more research to ensure value for money. This study aimed to compare the effectiveness of Risankizumab versus Adalimumab, the most commonly utilized biologic for managing psoriasis in Saudi Arabia.

METHODS: This study retrospectively compared the effectiveness and direct medical cost of Risankizumab and Adalimumab in treating chronic plaque psoriasis in adults from two Saudi Arabian healthcare centers. The Psoriasis Area and Severity Index (PASI) and body surface area (BSA) were used to assess treatment effectiveness, with patient data sourced from electronic medical records. Multiple regression analysis was performed to examine various factors affecting treatment outcomes. An economic evaluation was conducted to examine the cost-effectiveness of the two drugs, considering four scenarios with varying dosage patterns and costs. Analysis was performed from the perspective of public healthcare payers and considered all utilized health services.

RESULTS: The data for 70 patients were analyzed, with comparable baseline characteristics between groups. While Risankizumab led to a greater reduction in PASI scores and BSA affected, these results were not statistically significant. The annual treatment cost for Risankizumab was higher than Adalimumab. Various scenarios were studied, considering real acquisition costs, double dosing for Adalimumab, and the use of biosimilars. A scenario assuming double dosing for Adalimumab and a 40% discount for Risankizumab demonstrated both cost and efficacy advantages in 71.25% of cases.

CONCLUSIONS: This study compared the effectiveness and cost of Risankizumab and Adalimumab for treating chronic plaque psoriasis in Saudi Arabian hospitals. Although Risankizumab showed a greater reduction in symptoms, the difference was not statistically significant. However, under certain scenarios, Risankizumab demonstrated cost and efficacy advantages. These findings may influence treatment decisions for psoriasis, but further research is needed.

PMID:38071302 | DOI:10.1186/s12962-023-00504-1

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A randomized controlled trial comparing conventional and piezosurgery methods in mandibular bone block harvesting from the retromolar region

BMC Oral Health. 2023 Dec 9;23(1):986. doi: 10.1186/s12903-023-03739-9.

ABSTRACT

BACKGROUND: Although piezosurgery is now commonly used for various applications in maxillofacial surgery, its advantages over conventional rotary instruments in terms of postoperative edema, ecchymosis, postoperative morbidity, and prolonged osteotomy time have been questioned.

MATERIALS AND METHODS: This study aimed to compare the efficiency, postoperative morbidity, and complication rates of piezosurgery and conventional methods in harvesting autogenous ramus grafts. In this randomized controlled trial, 21 patients (32 sides) underwent autogenous graft harvesting from the ramus area, with 16 sites treated using piezosurgery and 16 using the conventional method. The primary outcomes measured were osteotomy time, total operation time, and postoperative morbidity. Complication rates were also evaluated.

RESULTS: The final analysis encompassed 19 patients, accounting for a total of 30 donor sites, following the exclusion of two patients who were unable to attend the scheduled follow-up visits. A total of 19 patients (30 donor sites) were included in the final analysis. No statistically significant difference was found in the mean osteotomy time between the piezosurgery group (mean: 10.35, SD: 2.74 min) and the conventional group (mean: 8.74, SD: 2.74 min) (95% CI: -3.67 to 0.442, p = 0.119). The total operation time, postoperative pain, and swelling were not significantly different between the two groups (p > 0.05). The complication rates, including wound dehiscence and inferior alveolar nerve exposure, were similar in both groups.

CONCLUSIONS: Piezosurgery can be safely used for harvesting autogenous ramus grafts and does not increase osteotomy or total operation time compared to the conventional method. The postoperative morbidity and complication rates were also similar, indicating that both techniques can be effectively employed in clinical practice.

CLINICAL TRIAL REGISTRATION: The protocol was registered on clinicaltrials.gov (ID: NCT05548049, First registration date: 21/09/2022).

PMID:38071300 | DOI:10.1186/s12903-023-03739-9

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Unveiling professional and personal preferences of early career dentists during first year of employment at the Thai dental public sector: a one-year cross-sectional study

BMC Oral Health. 2023 Dec 9;23(1):989. doi: 10.1186/s12903-023-03659-8.

ABSTRACT

BACKGROUND: Despite the implementation of various government policies to retain Thai dentists in public sector, a high turnover rate among early career dentists has persisted for decades. This study aims to explore factors relating to early career dentists’ choice of the public sector as their preferred workplace and decisions relating to staying, resigning, or relocating from the workplace after one-year employment.

METHODS: A one-year cross-sectional survey was conducted among Thai early career dentists who began working in 2020 using two sets of online questionnaires. The first survey assessed factors influencing dentists’ decision to choose the public sector as their preferred workplace at the beginning of the year. The second survey investigated factors influencing dentists’ decision to stay, resign, or relocate from the same workplace at one-year after employment. Descriptive statistics and multivariable binary logistic regression were used for data analysis.

RESULTS: A total of 198 early career dentists completed the online survey questionnaire at the starting point (December 2020-January 2021), and 186 dentists completed the one-year employment questionnaire. The living environment and provided amenities and facilities were the most influential factors in their decision to choose and remain in the public sector. Conversely, their attitude toward unrelated job descriptions and an increased opportunity to pursue postgraduate studies were the most relevant factors when deciding to relocate to a new workplace. Factors such as delayed authority in bureaucracy, hometown location, and being in relationship status were the most significant contributors to resignation from the public sector.

CONCLUSIONS: The major factors influencing dentists’ choice and retention in the public sector include the living environment, supportive supervisors and colleagues, and the availability of opportunities for further postgraduate education. Meanwhile, factors impacting retention after one year of work are related to hometown location and the bureaucracy system. Collaborations among ministries, tailored to each local community’s specific requirements, may enhance dentists’ retention in public sectors.

PMID:38071294 | DOI:10.1186/s12903-023-03659-8

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Addressing urinary incontinence by gender: a nationwide population-based study in Turkiye

BMC Urol. 2023 Dec 9;23(1):205. doi: 10.1186/s12894-023-01388-2.

ABSTRACT

BACKGROUND: Urinary incontinence (UI), which usually occurs in women but affects both sexes, is a significant public health challenge. This study aims to comprehensively investigate the prevalence and determinants of UI in men and women, considering gender-specific factors.

METHODS: The study performed a secondary analysis on data obtained from 13,383 individuals surveyed in the 2019 Turkish Health Survey, providing a representation of the Turkish population. The dataset included sociodemographic and health-related variables like UI, body mass index (BMI), physical activity, smoking, and chronic diseases-statistical analysis employed chi-square tests and gender-stratified logistic regression models to identify UI-associated factors.

RESULTS: Our results showed that UI affected 8.8% of the population, with a striking gender disparity. Women had a notably higher prevalence at 11.2%, while men had a lower rate of 5.5%. Importantly, this gender gap narrowed with age. For example, in the 34-44 age group, the female/male ratio was 6.9, but it decreased to 1.4 in the 65-74 age group. Marital status and employment status played significant roles. Separated, divorced, or widowed individuals, particularly women, had the highest prevalence at 19.3%. Employment status influenced UI prevalence, with employed men having the lowest rate (2.1%), while retired women faced the highest rate (15.0%). Higher BMI, especially in obese individuals, significantly raised UI prevalence, reaching 7.9% for men and 15.8% for women. Physical inactivity, notably in women (17.0%), and prolonged sedentary hours (13.9%) were associated with higher UI rates. Former smokers, especially women (15.9%), had a notable impact on UI. Poor perceived health and chronic conditions like Chronic Obstructive Pulmonary Disease (COPD), hypertension, and diabetes were significantly associated with higher UI prevalence. Logistic regression analysis revealed that age, education, perceived health status, COPD, and diabetes were significant factors associated with UI in both sexes, while in women, BMI, physical activity, and smoking also played notable roles.

CONCLUSIONS: This extensive UI study has unveiled notable gender disparities and determinants. Notably, these disparities decrease with age, underlining UI’s changing nature over time. Modifiable factors impact women more, while non-modifiable factors are linked to men. The study underscores the importance of tailoring healthcare strategies to address UI based on gender.

PMID:38071293 | DOI:10.1186/s12894-023-01388-2

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Comparison of breathing pattern and diaphragmatic motion in patients with unilateral cervical radiculopathy and asymptomatic group

BMC Pulm Med. 2023 Dec 9;23(1):498. doi: 10.1186/s12890-023-02804-x.

ABSTRACT

BACKGROUND: The associations between neck pain and respiratory dysfunction were clarified in patients with neck pain. There is dearth of evidence on pulmonary dysfunction and diaphragmatic excursion in patients with unilateral cervical radiculopathy (CR). The purpose of this study was to compare the breathing pattern and diaphragmatic excursion in patients with unilateral CR with those in an asymptomatic group.

METHODS: Twenty-five patients with unilateral CR and 25 asymptomatic individuals aged between 30 and 55 participated in this study. Diaphragmatic motion, breathing pattern, active cervical range of motion and kinesiophobia were investigated in both groups by using fluoroscopy, manual assessment of respiratory motion (MARM), cervical range of motion device, and Tampa scale of kinesiophobia. Statistical significance was set at 0.05.

RESULTS: No statistically significant differences were found between the two groups with regard to sex, age and body mass index. The mean excursion of the hemi diaphragm on the involved side (the side of CR) was significantly lower than that on the uninvolved side in patients with unilateral CR with a large effect size. The excursion of the involved hemi diaphragm in patients was reduced compared to the matched hemi diaphragm in the control group. There was no significant difference between the hemi diaphragms excursion in the control group. The results of the MARM variables showed that the volume of breathing and the percentage rib cage motion in normal and deep breathing were significantly different between the two groups, but there was no significant difference in the balance of breathing between the two groups. Additionally, the active cervical range of motion was reduced in these patients in comparison to the control group, and it was less on the involved side than on the uninvolved side.

CONCLUSION: The results of this study revealed a dysfunctional breathing pattern in normal and deep breathing and a unilateral reduction in diaphragmatic excursion on the side of radiculopathy in patients with unilateral CR compared to the control group.

PMID:38071289 | DOI:10.1186/s12890-023-02804-x

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Dementia subtypes, cognitive decline and survival among older adults attending a memory clinic in Cape Town, South Africa: a retrospective study

BMC Geriatr. 2023 Dec 9;23(1):829. doi: 10.1186/s12877-023-04536-3.

ABSTRACT

BACKGROUND: There are no published longitudinal studies from Africa of people with dementia seen in memory clinics. The aim of this study was to determine the proportions of the different dementia subtypes, rates of cognitive decline, and predictors of survival in patients diagnosed with dementia and seen in a memory clinic.

METHODS: Data were collected retrospectively from clinic records of patients aged ≥ 60 seen in the memory clinic at Groote Schuur Hospital, Cape Town, South Africa over a 10-year period. Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria were used to identify patients with Major Neurocognitive Disorders (dementia). Additional diagnostic criteria were used to determine the specific subtypes of dementia. Linear regression analysis was used to determine crude rates of cognitive decline, expressed as mini-mental state examination (MMSE) points lost per year. Changes in MMSE scores were derived using mixed effects modelling to curvilinear models of cognitive change, with time as the dependent variable. Multivariable cox survival analysis was used to determine factors at baseline that predicted mortality.

RESULTS: Of the 165 patients who met inclusion criteria, 117(70.9%) had Major Neurocognitive Disorder due to Alzheimer’s disease (AD), 24(14.6%) Vascular Neurocognitive Disorder (VND), 6(3.6%) Dementia with Lewy Bodies (DLB), 5(3%) Parkinson disease-associated dementia (PDD), 3(1.8%) fronto-temporal dementia, 4(2.4%) mixed dementia and 6(3.6%) other types of dementia. The average annual decline in MMSE points was 2.2(DLB/PDD), 2.1(AD) and 1.3(VND). Cognitive scores at baseline were significantly lower in patients with 8 compared to 13 years of education and in those with VND compared with AD. Factors associated with shorter survival included age at onset greater than 65 (HR = 1.82, 95% C.I. 1.11, 2.99, p = 0.017), lower baseline MMSE (HR = 1.05, 95% C.I. 1.01, 1.10, p = 0.029), Charlson’s comorbidity scores of 3 to 4 (HR = 1.88, 95% C.I. 1.14, 3.10, p = 0.014), scores of 5 or more (HR = 1.97, 95% C.I. 1.16, 3.34, p = 0.012) and DLB/PDD (HR = 3.07, 95% C.I. 1.50, 6.29, p = 0.002). Being female (HR = 0.59, 95% C.I.0.36, 0.95, p = 0.029) was associated with longer survival.

CONCLUSIONS: Knowledge of dementia subtypes, the rate and factors affecting cognitive decline and survival outcomes will help inform decisions about patient selection for potential future therapies and for planning dementia services in resource-poor settings.

PMID:38071284 | DOI:10.1186/s12877-023-04536-3