bluuebunny/crossref_metadata_2025 huggingface dataset:
Branched-chain amino acids supplementation improves liver frailty index in frail compensated cirrhotic patients: a randomized controlled trial
Authors: Siramolpiwat Sith , Limthanetkul Nisakorn , Pornthisarn Bubpha , Vilaichone Ratha-korn , Chonprasertsuk Soonthorn , Bhanthumkomol Patommatat , Nunanan Pongjarat , Issariyakulkarn Navapan
Published: May 2023

Background

Physical frailty is related with morbidity and mortality in patients with cirrhosis. Currently, there is no approved treatment of frailty in these patients. Here, we evaluated the efficacy of 16 weeks branched-chain amino acids (BCAA) supplementation on frailty in frail compensated cirrhotic patients.

Methods

After a 4-week run-in period consisted of dietary and exercise counseling, compensated cirrhotic patients with frailty, defined by liver frailty index (LFI)≥4.5, were randomly assigned (1:1) to BCAA or control group. The BCAA group received twice daily BCAAs supplementation (210 kcal, protein 13.5 g, BCAA 2.03 g) for 16 weeks. The primary outcome was frailty reversion. The secondary outcomes were changes in biochemistries, body composition evaluated by bioelectrical impedance analysis, and quality of life (QoL).

Results

54 patients were prospectively enrolled (age 65.5 ± 9.9 years, 51.9% female, Child-Pugh A/B 68.5%/31.5%, MELD 10.3 ± 3.1). Baseline characteristics were similar between both groups. At week 16, BCAA group had a significant improvement in LFI (-0.36 ± 0.3 vs. -0.15 ± 0.28, P = 0.01), BMI (+ 0.51 ± 1.19 vs. -0.49 ± 1.89 kg/m2, P = 0.03), and serum albumin (+ 0.26 ± 0.27 vs. +0.06 ± 0.3 g/dl, P = 0.01). The proportion of frailty reversion at week 16 was significantly higher in BCAA group (36% vs. 0%, P < 0.001). Compared with baseline, BCAA group had a significant increase in skeletal muscle index (7.5 ± 1.6 to 7.8 ± 1.5 kg/m2, P = 0.03). Regarding the QoL, only the BCAA group had a significant improvement in all 4 domains of physical component score of the SF-36 questionnaire.

Conclusions

A 16-week BCAA supplementation improved frailty in frail compensated cirrhotic patients. In addition, this intervention resulted in an improvement of muscle mass and physical domain of QoL in these patients.

Trial registration

This study was registered with Thai Clinical Trial Registry (TCTR20210928001;https://www.thaiclinicaltrials.org/#).
Neuron-specific enolase in hypertension patients with acute ischemic stroke and its value forecasting long-term functional outcomes
Authors: Gao Lingfei , Xie Jiali , Zhang Haiqin , Zheng Hangqi , Zheng Wanjun , Pang Chunyang , Cai Yunlei , Deng Binbin
Published: May 2023

Background

Neuron Specific Enolase (NSE), a neuro-biochemical protein marker, may correlate with the prognosis of stroke patients. Moreover, hypertension is the most common comorbidities in patients with acute ischemic stroke (AIS), and the relationship between NSE levels and long-term functional outcomes in such an increasingly large population is unclear. The aim of the study was to investigate the relationships mentioned above and optimize the prediction models.

Methods

From 2018 to 2020, 1086 admissions for AIS were grouped as hypertension and non-hypertension, while hypertension group was randomly divided into development and validation cohorts for internal validation. The severity of the stroke was staged by National Institutes of Health Stroke Scale (NIHSS) score. Stroke prognosis after 1 year of follow up was documented by modified Rankin Scale (mRS) score.

Results

Analysis revealed the following findings:(i) Serum NSE levels increased greatly in hypertension subjects with poor functional outcomes(p = 0.046). However, there was no association in non-hypertension individuals(p = 0.386). (ii) In addition to the conventional factors (age and NIHSS score), NSE (OR:1.241, 95% CI: 1.025–1.502) and prothrombin time were significantly related to the incidence of unfavorable outcomes. (iii)Based on the above four indicators, a novel nomogram was established to predict the prognosis of stoke in hypertension patients with the c-index values of 0.8851.

Conclusions

Overall, high baseline NSE is associated with poor 1-year AIS outcomes in hypertension patients, suggesting NSE may be a potential prognostic and therapeutic target for stroke in hypertension patients.
Collateral circulation caused by end-stage hepatic alveolar echinococcosis
Authors: Jiang Tiemin , Aji Tuerganaili , Ran Bo , Guo Qiang , Zhang Ruiqing , Ahan Ayifuhan , Abulizi Abuduaini , Tuergan Talaiti , Shao Yingmei , Wen Hao
Published: May 2023

Background

Hepatic alveolar echinococcosis (HAE), as a benign parasitic disease with malignant infiltrative activity, grows slowly in the liver, allowing sufficient time for collateral vessels to emerge in the process of vascular occlusion.

Methods

The portal vein (PV), hepatic vein and hepatic artery were observed by enhanced CT and the inferior vena cava (IVC) by angiography, respectively. Analysis of the anatomical characteristics of the collateral vessels helped to look into the pattern and characteristics of vascular collateralization caused by this specific etiology.

Results

33, 5, 12 and 1 patients were included in the formation of collateral vessels in PV, hepatic vein, IVC and hepatic artery, respectively. PV collateral vessels were divided into two categories according to different pathways: type I: portal -portal venous pathway (13 cases) and type II: type I incorporates a portal-systemic circulation pathway (20 cases). Hepatic vein (HV) collateral vessels fell into short hepatic veins. The patients with IVC collateral presented with both vertebral and lumbar venous varices. Hepatic artery collateral vessels emanating from the celiac trunk maintains blood supply to the healthy side of the liver.

Conclusions

Due to its special biological nature, HAE exhibited unique collateral vessels that were rarely seen in other diseases. An in-depth study would be of great help to improve our understanding related to the process of collateral vessel formation due to intrahepatic lesions and its comorbidity, in addition to providing new ideas for the surgical treatment of end-stage HAE.
Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi
Authors: Wadhwa Bharti , Malhotra Vikas , Kerai Sukhyanti , Husain Farah , Pandey Nalini Bala , Saxena Kirti N. , Singh Vinay , Quinn Tom M. , Li Feng , Gaughan Erin , Shankar-Hari Manu , Mills Bethany , Antonelli Jean , Bruce Annya , Finlayson Keith , Moore Anne , Dhaliwal Kevin , Edwards Christopher
Published: May 2023

Background

In this phase 2 randomised placebo-controlled clinical trial in patients with COVID-19, we hypothesised that blocking mineralocorticoid receptors using a combination of dexamethasone to suppress cortisol secretion and spironolactone is safe and may reduce illness severity.

Methods

Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50 mg day 1, then 25 mg once daily for 21 days) or standard of care in a 2:1 ratio. Both groups received dexamethasone 6 mg daily for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category ≤ 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF).

Results

One hundred twenty patients with PCR confirmed COVID were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had significantly lower D-dimer levels on days 4 and 7 (day 7 mean D-dimer: SpiroDex 1.15 µg/mL, Dex 3.15 µg/mL, p = 0.0004) and aldosterone at day 7 (SpiroDex 6.8 ng/dL, Dex 14.52 ng/dL, p = 0.0075). There was no difference in VWF or angiotensin II levels between groups. For secondary outcomes, SpiroDex patients had a significantly greater number of oxygen free days and reached oxygen freedom sooner than the Dex group. Cough scores were no different during the acute illness, however the SpiroDex group had lower scores at day 28. There was no difference in corticosteroid levels between groups. There was no increase in adverse events in patients receiving SpiroDex.

Conclusion

Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-dimer and aldosterone. Time to recovery was not significantly reduced. Phase 3 randomised controlled trials with spironolactone and dexamethasone should be considered.

Trial registration

The trial was registered on the Clinical Trials Registry of India TRI: CTRI/2021/03/031721, reference: REF/2021/03/041472. Registered on 04/03/2021.
Association between red cell distribution width-to-platelet ratio and short-term and long-term mortality risk in patients with acute ischemic stroke
Authors: Xu Nan , Peng Cao
Published: May 2023

Background

The objective of this study was to evaluate the association between red cell distribution width/platelet ratio (RPR) and 30-day and 1-year mortality in acute ischemic stroke (AIS).

Methods

Data for the retrospective cohort study were collected from the Medical Information Mart for Intensive Care (MIMIC) III database. RPR was divided into two groups: RPR ≤ 0.11 and RPR > 0.11. The study outcomes were 30-day mortality and 1-year mortality from AIS. Cox proportional hazard models were utilized to assess the association between RPR and mortality. Subgroup analyses were applied based on age, tissue-type plasminogen activator (IV-tPA), endovascular treatment, and myocardial infarction.

Results

A total of 1,358 patients were included in the study. Short- and long-term mortality occurred in 375 (27.61%) and 560 (41.24%) AIS patients, respectively. A high RPR was significantly associated with increased 30-day [hazard ratio (HR): 1.45, 95% confidence interval (CI): 1.10 to 1.92, P = 0.009] and 1-year mortality (HR: 1.54, 95%CI: 1.23 to 1.93, P < 0.001) in AIS patients. Meanwhile, RPR was found to be significantly related to 30-day mortality in AIS patients aged < 65 years (HR: 2.19, 95% CI: 1.17 to 4.10, P = 0.014), without IV-tPA use (HR: 1.42, 95% CI: 1.05 to 1.90, P = 0.021), without using endovascular treatment (HR: 1.45, 95% CI: 1.08 to 1.94, P = 0.012), and without myocardial infarction (HR: 1.54, 95% CI: 1.13 to 2.10, P = 0.006). Additionally, RPR was associated with 1-year mortality in AIS patients aged < 65 years (HR: 2.54, 95% CI: 1.56 to 4.14, P < 0.001), aged ≥ 65 years (HR: 1.38, 95% CI: 1.06 to 1.19, P = 0.015), with (HR: 1.46, 95% CI: 1.15 to 1.85, P = 0.002) and without using IV-tPA (HR: 2.30, 95% CI: 1.03 to 5.11, P = 0.041), without using endovascular treatment (HR: 1.56, 95% CI: 1.23 to 1.96, P < 0.001), and without myocardial infarction (HR: 1.68, 95% CI: 1.31 to 2.15, P < 0.001).

Conclusion

Elevated RPR is associated with a high risk of short-term and long-term mortality in AIS.
Cost-effectiveness of first-line immunotherapy combinations with or without chemotherapy for advanced non–small cell lung cancer: a modelling approach
Authors: Hui Wen , Song Ruomeng , Tao Hongyu , Gao Zhixiang , Zhu Min , Zhang Mingyue , Wu Huazhang , Gong Daichen , Zhang Xiyan , Cai Yuanyi
Published: May 2023

Background

Many studies have explored the cost-effectiveness of immunotherapy versus chemotherapy alone. However, there is paucity of evidence on direct pharmacoeconomic studies related to immunotherapy combinations. Thus, we aimed at assessing the economic outcomes of first-line immunotherapy combinations in the treatment of advanced non-small cell lung cancer (NSCLC) from the Chinese health care perspective.

Methods

The mutual hazard ratios (HRs) of ten immunotherapy combinations and one chemotherapy regimen for the overall survival (OS) and progression-free survival (PFS) were obtained from a network meta-analysis. Based on proportional hazard (PH) assumption, adjusted OS and PFS curves were established to make the effects comparable. With the parameters of cost and utility, and of scale and shape from the fit of adjusted OS and PFS curves obtained from previous studies, a partitioned survival model was designed to estimate the cost-effectiveness of immunotherapy combinations versus chemotherapy alone. Parameter uncertainty in model inputs was assessed using one-way deterministic and probabilistic sensitivity analyses.

Results

The incremental cost of camrelizumab plus chemotherapy versus chemotherapy alone was $13,180.65, the lowest among all the other immunotherapy combinations. Furthermore, sintilimab plus chemotherapy (sint-chemo) provided the highest quality-adjusted life-year (QALY) benefit versus chemotherapy alone (incremental QALYs = 0.45). Sint-chemo yielded the best incremental cost-effectiveness ratio (ICER) versus chemotherapy alone (ICER = $34,912.09/QALY), at the current price. The cost-effectiveness probabilities were 32.01% and 93.91% for pembrolizumab plus chemotherapy, and atezolizumab plus bevacizumab plus chemotherapy, respectively (if the original price of the pembrolizumab, atezolizumab, and bevacizumab were decreased by 90%).

Conclusions

Based on the fact that there is fierce competition in the PD-1/PD-L1 market, pharmaceutical enterprises should strive for greater efficacy, and optimal pricing strategy for therapies.
An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
Authors: Yamada Yosuke , Simon Ronald , Iwane Kosuke , Nakanishi Yuki , Takeuchi Yasuhide , Yoshizawa Akihiko , Takada Masahiro , Toi Masakazu , Haga Hironori , Marx Alexander , Sauter Guido
Published: May 2023

Background

Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In addition, immunohistochemistry (IHC) has identified POU2F3-positive cells in the normal human breast, suggesting the presence of tuft cells in this organ.

Methods

Here, we (i) reviewed previously identified POU2F3-positive invasive breast cancers (n = 4) for POU2F3 expression in intraductal cancer components, (ii) investigated a new cohort of invasive breast cancers (n = 1853) by POU2F3-IHC, (iii) explored POU2F3-expressing cells in non-neoplastic breast tissues obtained from women with or without BRCA1 mutations (n = 15), and (iv) reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from normal breast cells.

Results

Two TNBCs of the four previously reported invasive POU2F3-positive breast cancers contained POU2F3-positive ductal carcinoma in situ (DCIS). In the new cohort of invasive breast cancers, IHC revealed four POU2F3-positive cases, two of which were triple-negative, one luminal-type, and one triple-positive. In addition, another new POU2F3-positive tumor with a triple-negative phenotype was found in daily practice. All non-neoplastic breast tissues contained POU2F3-positive cells, irrespective of BRCA1 status. The scRNA-seq reanalysis confirmed POU2F3-expressing epithelial cells (3.3% of all epithelial cells) and the 17% that co-expressed the other two tuft cell-related markers (SOX9/AVIL or SOX9/GFI1B), which suggested they were bona fide tuft cells. Of note, SOX9 is also known as the “master regulator” of TNBCs.

Conclusions

POU2F3 expression defines small subsets in various breast cancer subtypes, which can be accompanied by DCIS. The mechanistic relationship between POU2F3 and SOX9 in the breast warrants further analysis to enhance our understanding of normal breast physiology and to clarify the significance of the tuft cell-like phenotype for TNBCs.
Ophthalmic manifestations in children with Down Syndrome in Bogotá, Colombia
Authors: Rojas‑Carabali William , Cortés-Albornoz María Camila , Flórez‑Esparza Gabriela , Cifuentes‑González Carlos , de‑la‑Torre Alejandra , Talero‑Gutiérrez Claudia
Published: May 2023

Background

To describe the ocular features of a cohort of children with Down Syndrome (DS) in Bogotá, Colombia.

Methods

We performed a cross-sectional study, evaluating 67 children with DS. A pediatric ophthalmologist performed a complete optometric and ophthalmological evaluation of each child, including visual acuity, ocular alignment, external eye examination, biomicroscopy, auto-refractometry, retinoscope in cycloplegia, and fundus examination. Results were reported as frequency distribution tables with percentages for categorical variables and means and standard deviation or median and interquartile ranges for continuous variables, according to their distribution. We used the Chi-square test or Fisher’s exact test for categorical variables and ANOVA or Kruskal–Wallis for continuous variables when indicated.

Results

A total of 134 eyes from 67 children were evaluated. Males represented 50.7%. The children’s age ranged from 8–16 years, with a mean of 12.3 (SD 2.30). The most frequent refractive diagnosis per eye was hyperopia (47%), followed by myopia (32.1%) and mixed astigmatism (18.7%). The most frequent ocular manifestations were oblique fissure (89.6%), followed by amblyopia (54.5%) and lens opacity (39.4%). Female sex was associated with strabismus (P = 0.009) and amblyopia (P = 0.048).

Conclusion

Our cohort had a high prevalence of disregarded ophthalmological manifestations. Some of these manifestations, such as amblyopia, can be irreversible and severely affect the neurodevelopment of DS children. Therefore, ophthalmologists and optometrists should be aware of the visual and ocular affection of children with DS to assess and provide appropriate management. This awareness could improve rehabilitation outcomes for these children.
Initial postoperative plasticity as a predictor of mid-term stereoacuity outcome after surgery for intermittent exotropia
Authors: Liu Peipei , Fu Jing , Zhang Ronghan , Chu Hang
Published: May 2023

Background

Intermittent exotropia (IXT) would cause different degrees of damage to stereopsis. We aimed to introduce a visual perception plasticity score (VPPS) that reflects initial postoperative plasticity and evaluate its effectiveness in predicting the mid-term surgical outcome in IXT patients.

Methods

A total of 149 patients with intermittent exotropia who underwent surgery in November 2018 and October 2019 were recruited. All subjects underwent detailed ocular examinations before and after surgery. VPPS were calculated based on visual perception examination system at one week postoperatively. Demographic, angle of deviation and stereopsis were collected and analyzed with regard to the VPPSs preoperatively and at one week, one month, three months, six months postoperatively. Predictive performances of VPPS were assessed using receiver operating characteristic (ROC) curves, the area under the curve (AUC) and cut-offs were obtained.

Results

Of the 149 patients, the average deviation was 43Δ at distance and 46Δ at near. The average rate of normal stereopsis before surgery was 22.81% at distance and 29.53% at near. Higher VPPS was associated with preoperative better near stereoacuity (r = 0.362, p = 0.000), less angle of deviation at distance (r=-0.164, p = 0.046), and better near (r = 0.400, p = 0.000) and distant stereoacuity (r = 0.321, p = 0.000) during the early postoperative period (1 week). The areas under the curves suggested that VPPS could be an effective predictor of sensory outcome(AUC>0.6). Cut-off values of 50 and 80 were calculated for VPPS using ROC curve analysis.

Conclusion

Higher VPPSs were associated with a greater possibility of stereopsis improvement in patients with IXT. VPPS is a potentially promising indicator to predict the mid-term surgical outcome of intermittent exotropia.
Diffusion of a micronutrient home fortification program for infants and toddlers in a multi-ethnic population in rural western China
Authors: Ye Ruixue , Wu Yuju , Sun Chang , Wang Qingzhi , Mao Yuping , Zhou Huan , Raat Hein
Published: May 2023

Background

The micronutrient home fortification programs contribute to the prevention of childhood anemia. WHO suggested applying culturally appropriate strategies to implement the micronutrient home fortification programs in various communities. However, there is little knowledge on evidence-based effective diffusion strategies of the micronutrient home fortification programs in multi-ethnic populations. This study aims to examine the diffusion of a micronutrient home fortification program with micronutrient powder (MNP) in a multi-ethnic population by investigating factors associated with being an ‘early’ or a ‘later’ adopter of MNP.

Methods

We conducted a cross-sectional study in rural western China. Multistage sampling was used to select children’s caregivers in Han, Tibetan, and Yi ethnic communities (N = 570). The diffusion of innovations theory informed the data collection on caregivers’ decision process and was applied to classify participants into the MNP adopter categories of ‘leaders’, ‘followers’, ‘loungers’, and ‘laggards’. The ordered logistic regression model estimated the factors associated with the MNP adopter categories.

Results

Caregivers from the Yi ethnic subgroup were likely to adopt MNP relatively late (AOR = 1.67; 95%CI = 1.09, 2.54) compared with Han and Tibetan ethnic subgroups. Caregivers with more knowledge regarding the MNP feeding method (AOR = 0.71; 95%CI = 0.52, 0.97) and those with stronger self-efficacy in adopting MNP (AOR = 0.85; 95%CI = 0.76, 0.96) were more likely to adopt MNP earlier than others. The following messages and channels also tend to make caregivers adopt MNP earlier: hearing that ‘MNP was free’ from villagers (AOR = 0.45; 95%CI = 0.20, 0.98), and learning ‘MNP feeding method’ from township doctors (AOR = 0.16; 95%CI = 0.06, 0.48).

Conclusions

Disparities in adopting MNP existing among different ethnic groups require more effective diffusion strategies in disadvantaged minority ethnic groups. Enhancing self-efficacy in adopting MNP and knowledge on feeding method of MNP have the potential to make caregivers adopt MNP earlier. Peer networks and township doctors can be effective agencies to facilitate the diffusion and adoption of MNP.
Barriers to oral care: a cross-sectional analysis of the Canadian longitudinal study on aging (CLSA)
Authors: De Rubeis Vanessa , Jiang Ying , de Groh Margaret , Dufour Lisette , Bronsard Annie , Morrison Howard , Bassim Carol W.
Published: May 2023

Background

Oral health plays a role in overall health, indicating the need to identify barriers to accessing oral care. The objective of this study was to identify barriers to accessing oral health care and examine the association between socioeconomic, psychosocial, and physical measures with access to oral health care among older Canadians.

Methods

A cross-sectional study was conducted using data from the Canadian Longitudinal Study on Aging (CLSA) follow-up 1 survey to analyze dental insurance and last oral health care visit. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between socioeconomic, psychosocial, and physical measures with access to oral care, measured by dental insurance and last oral health visit.

Results

Among the 44,011 adults included in the study, 40% reported not having dental insurance while 15% had not visited an oral health professional in the previous 12 months. Several factors were identified as barriers to accessing oral health care including, no dental insurance, low household income, rural residence, and having no natural teeth. People with an annual income of <$50,000 were four times more likely to not have dental insurance (adjusted OR: 4.09; 95% CI: 3.80–4.39) and three times more likely to report not visiting an oral health professional in the previous 12 months (adjusted OR: 3.07; 95% CI: 2.74–3.44) compared to those with annual income greater than $100,000.

Conclusions

Identifying barriers to oral health care is important when developing public health strategies to improve access, however, further research is needed to identify the mechanisms as to why these barriers exist.
Effects of blue-light LED toothbrush on reducing dental plaque and gingival inflammation in orthodontic patients with fixed appliances: a crossover randomized controlled trial
Authors: Manphibool Chavirakarn , Matangkasombut Oranart , Chantarangsu Soranun , Chantarawaratit Pintu-on
Published: May 2023

Background

Patients with fixed orthodontic appliances have higher plaque accumulation and gingival inflammation. Our aim was to compare the effectiveness of a light emitting diode (LED) toothbrush with a manual toothbrush in reducing dental plaque and gingival inflammation in orthodontic patients with fixed appliances, and to investigate the effect of the LED toothbrush on Streptococcus mutans (S. mutans) biofilm in vitro.

Methods

Twenty-four orthodontic patients were recruited and randomly assigned into 2 groups: (1) started with manual and (2) started with LED toothbrushes. After a 28-day usage and 28-day wash-out period, the patients switched to the other intervention. The plaque and gingival indices were determined at baseline and 28 days after each intervention. The patients’ compliance and satisfaction scores were collected using questionnaires. For the in vitro experiments, S. mutans biofilm was divided into 5 groups (n = 6) with 15-, 30-, 60-, or 120-sec LED exposure, and without LED exposure as a control group.

Results

There was no significant difference in the gingival index between the manual and LED toothbrush groups. The manual toothbrush was significantly more effective in reducing the plaque index in the proximal area on the bracket side (P = 0.031). However, no significant difference was found between the two groups in other areas around the brackets or on the non-bracket side. After LED exposure in vitro, the percentages of bacterial viability after LED exposure for 15–120 s were significantly lower compared with the control (P = 0.006).

Conclusion

Clinically, the LED toothbrush was not more effective in reducing dental plaque or gingival inflammation than the manual toothbrush in orthodontic patients with fixed appliances. However, the blue light from the LED toothbrush significantly reduced the number of S. mutans in biofilm when it was exposed to the light for at least 15 s in vitro.

Clinical Trial Registration

Thai Clinical Trials Registry (TCTR20210510004). Registered 10/05/2021.
Impact of the number of cycles of platinum-based chemotherapy for early stage ovarian clear cell carcinoma on survival: a retrospective study
Authors: Gao Yang
Published: May 2023

Background

Ovarian clear cell carcinoma (OCCC) is a unique subtype of ovarian epithelial ovarian cancer. The number of chemotherapy cycles for early-stage patients is still debated. This study aimed to evaluate whether at least 4 cycles of adjuvant platinum-based chemotherapy have better prognostic value than 1–3 cycles in early-stage OCCC.

Methods

We retrospectively retrieved data from 102 patients with stage I-IIA OCCC between 2008 and 2017. All patients underwent complete surgical staging followed by adjuvant platinum-based chemotherapy. Kaplan-Meier curves and Multivariate Cox analysis were performed to estimate 5-year overall survival (OS) and progression-free (PFS) according to the number of chemotherapy cycles.

Results

Among stage I-IIA disease, twenty (19.6%) patients received 1–3 cycles, and eighty-two (80.4%) patients received at least 4 cycles of adjuvant chemotherapy. Univariate analysis revealed that the patients in 1-3cycles group had not significantly improved 5-year OS and PFS than those in the ≥ 4 cycles group (5-year OS: hazard ratio [HR] 1.21; 95% confidence interval [CI] 0.25– 5.78, p = 0.1), and 5-year PFS: HR 0.79; 95% CI 0.26– 2.34, p = 0.1). In the multivariate analysis, there was no impact of 1–3 versus ≥ 4 cycles of chemotherapy on 5-year OS (HR 1.21, 95% CI 0.25–3.89, p = 0.8) or 5-year PFS (HR 0.94, 95% CI 0.32–2.71, p = 0.9). The potential independent risk factors associated with 5-year OS and PFS included the surgery approach and FIGO stage.

Conclusion

The number of cycles of platinum-based chemotherapy could not be associated with a survival benefit for patients with early-stage OCCC.
FAIRness through automation: development of an automated medical data integration infrastructure for FAIR health data in a maximum care university hospital
Authors: Parciak Marcel , Suhr Markus , Schmidt Christian , Bönisch Caroline , Löhnhardt Benjamin , Kesztyüs Dorothea , Kesztyüs Tibor
Published: May 2023

Background

Secondary use of routine medical data is key to large-scale clinical and health services research. In a maximum care hospital, the volume of data generated exceeds the limits of big data on a daily basis. This so-called “real world data” are essential to complement knowledge and results from clinical trials. Furthermore, big data may help in establishing precision medicine. However, manual data extraction and annotation workflows to transfer routine data into research data would be complex and inefficient. Generally, best practices for managing research data focus on data output rather than the entire data journey from primary sources to analysis. To eventually make routinely collected data usable and available for research, many hurdles have to be overcome. In this work, we present the implementation of an automated framework for timely processing of clinical care data including free texts and genetic data (non-structured data) and centralized storage as Findable, Accessible, Interoperable, Reusable (FAIR) research data in a maximum care university hospital.

Methods

We identify data processing workflows necessary to operate a medical research data service unit in a maximum care hospital. We decompose structurally equal tasks into elementary sub-processes and propose a framework for general data processing. We base our processes on open-source software-components and, where necessary, custom-built generic tools.

Results

We demonstrate the application of our proposed framework in practice by describing its use in our Medical Data Integration Center (MeDIC). Our microservices-based and fully open-source data processing automation framework incorporates a complete recording of data management and manipulation activities. The prototype implementation also includes a metadata schema for data provenance and a process validation concept. All requirements of a MeDIC are orchestrated within the proposed framework: Data input from many heterogeneous sources, pseudonymization and harmonization, integration in a data warehouse and finally possibilities for extraction or aggregation of data for research purposes according to data protection requirements.

Conclusion

Though the framework is not a panacea for bringing routine-based research data into compliance with FAIR principles, it provides a much-needed possibility to process data in a fully automated, traceable, and reproducible manner.
The sexuality experience of stoma patients: a meta-ethnography of qualitative research
Authors: Lin Siting , Yin Guo , Chen Linghui
Published: May 2023

Background

As the quality of life of stoma patients has become a research hotspot, sexual health as an integral part of patients’ lives has received more and more attention. However, there is a lack of comprehensive reviews on the sexual experiences of patients with stomas. This study aims to synthesize the qualitative literature on the subjective experience of stoma patients’ sexual life, to identify their sexual needs, and to provide evidence for the content and methods of sexual health interventions for healthcare professionals.

Methods

PubMed, Embase, Web of Science, CINAHL, and Scopus were searched for qualitative studies on the sexual experience of stoma patients (from the inception to January 2023). Titles, abstracts, and full texts were reviewed by two researchers. We used the Critical Appraisal Program (CASP) checklist to assess the quality of included articles.

Results

A total of 1388 articles were retrieved, and eight studies were included. Data was extracted, including three main themes: 1) sexual problems due to changes in physical function and psychological disorders; 2) the relationship with spouse changes; 3) the cognition of sexual life and the need for sexual knowledge.

Conclusion

Healthcare professionals should pay attention to the sexual life status and sexual health needs of stoma patients and their partners, and give professional guidance and support in treatment and nursing to improve the quality of sexual life of stoma patients.
Statistical analysis of high-dimensional biomedical data: a gentle introduction to analytical goals, common approaches and challenges
Authors: Rahnenführer Jörg , De Bin Riccardo , Benner Axel , Ambrogi Federico , Lusa Lara , Boulesteix Anne-Laure , Migliavacca Eugenia , Binder Harald , Michiels Stefan , Sauerbrei Willi , McShane Lisa ,   for topic group “High-dimensional data” (TG9) of the STRATOS initiative
Published: May 2023

Background

In high-dimensional data (HDD) settings, the number of variables associated with each observation is very large. Prominent examples of HDD in biomedical research include omics data with a large number of variables such as many measurements across the genome, proteome, or metabolome, as well as electronic health records data that have large numbers of variables recorded for each patient. The statistical analysis of such data requires knowledge and experience, sometimes of complex methods adapted to the respective research questions.

Methods

Advances in statistical methodology and machine learning methods offer new opportunities for innovative analyses of HDD, but at the same time require a deeper understanding of some fundamental statistical concepts. Topic group TG9 “High-dimensional data” of the STRATOS (STRengthening Analytical Thinking for Observational Studies) initiative provides guidance for the analysis of observational studies, addressing particular statistical challenges and opportunities for the analysis of studies involving HDD. In this overview, we discuss key aspects of HDD analysis to provide a gentle introduction for non-statisticians and for classically trained statisticians with little experience specific to HDD.

Results

The paper is organized with respect to subtopics that are most relevant for the analysis of HDD, in particular initial data analysis, exploratory data analysis, multiple testing, and prediction. For each subtopic, main analytical goals in HDD settings are outlined. For each of these goals, basic explanations for some commonly used analysis methods are provided. Situations are identified where traditional statistical methods cannot, or should not, be used in the HDD setting, or where adequate analytic tools are still lacking. Many key references are provided.

Conclusions

This review aims to provide a solid statistical foundation for researchers, including statisticians and non-statisticians, who are new to research with HDD or simply want to better evaluate and understand the results of HDD analyses.
Construction of a CCL20-centered circadian-signature based prognostic model in cervical cancer
Authors: Yu Yuchong , Liu Yao , Li Yuhong , Yang Xiaoming , Han Mi , Fan Qiong
Published: May 2023

Background

Rather low vaccination rates for Human papillomavirus (HPV) and pre-existing cervical cancer patients with limited therapeutic strategies ask for more precise prognostic model development. On the other side, the clinical significance of circadian clock signatures in cervical cancer lacks investigation.

Methods

Subtypes classification based upon eight circadian clock core genes were implemented in TCGA-CESC through k-means clustering methods. Afterwards, KEGG, GO and GSEA analysis were conducted upon differentially expressed genes (DEGs) between high and low-risk groups, and tumor microenvironment (TME) investigation by CIBERSORT and ESTIMATE. Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis. Lastly, FISH and IHC were used for validation of CCL20 expression in patients’ specimens and U14 subcutaneous tumor models were built for TME composition.

Results

We successfully classified cervical patients into high-risk and low-risk groups based upon circadian-oscillation-signatures. Afterwards, we built a prognostic risk model composed of GJB2, CCL20 and KRT24 with excellent predictive value on patients’ overall survival (OS). We then proposed metabolism unbalance, especially for glycolysis, and immune related pathways to be major enriched signatures between the high-risk and low-risk groups. Then, we proposed an ‘immune-desert’-like suppressive myeloid cells infiltration pattern in high-risk group TME and verified its resistance to immunotherapies. Finally, CCL20 was proved positively correlated with real-world patients’ stages and induced significant less CD8+ T cells and more M2 macrophages infiltration in mouse model.

Conclusions

We unraveled a prognostic risk model based upon circadian oscillation and verified its solidity. Specifically, we unveiled distinct TME immune signatures in high-risk groups.
Knowledge, attitudes, and practices of mothers regarding childhood malaria in southeastern Gabon
Authors: Lendongo Wombo Judicaël Boris , Mbani Mpega Ntigui Chérone Nancy , Oyegue-Liabagui Lydie Sandrine , Ibinga Euloge , Maghendji-Nzondo Sydney , Mounioko Franck , Ontoua Steede Seinnat , Okouga Alain Prince , Lekana-Douki Jean Bernard , Ngoungou Edgard Brice
Published: May 2023

Background

In Gabon, children under 5 years of age and pregnant women are the populations who are most at risk of malaria. Despite the presence of accessible health facilities, the community-based management of childhood fever remains a very common practice in Gabon, which may have serious consequences on child health. As such, the objective of this descriptive cross-sectional survey is to assess the mothers’ perception and knowledge of malaria and its severity.

Methods

Different households were selected using the simple random sampling method.

Results

A total of 146 mothers from different households were interviewed in the city of Franceville, in southern Gabon. Among the households interviewed, 75.3% had a low monthly income (below the minimum monthly income of $272.73). Among the respondents, 98.6% of mothers had heard of malaria and 55.5% had heard of severe malaria. Regarding preventive measures, 83.6% of mothers used an insecticide-treated net as a means of protection. Self-medication was practiced by 68.5% of women (100/146).

Discussion

The use of health facilities was motivated by better care, the decision of the head of the family, but above all by the severity of the disease. Women identified fever as the main symptom of malaria, which could be beneficial for a quicker and more efficient management of the disease in children. Malaria educational campaigns should also increase awareness of severe forms of malaria and its manifestations. This study shows that Gabonese mothers react quickly when their children have fever. However, several external factors lead them to practice self-medication as a first resort. In this survey population, the practice of self-medication did not depend on social status, marital status, level of education, on the young age or inexperience of mothers (p > 0.05).

Conclusions

The data revealed that mothers may underestimate severe malaria and delay medical care by self-medicating, which can have detrimental effects for children and hinder the regression of the disease.
Necrotising pneumonia caused by Curvularia hawaiiensis (syn. Bipolaris hawaiiensis) and Mycobacterium tuberculosis coinfection in a patient with ascariasis: a case report and review
Authors: Aguirre Cristina , Acosta-España Jaime David , Patajalo-Villata Sheila Jissela , Rodriguez-Morales Alfonso J.
Published: May 2023

Introduction

Curvularia hawaiiensis (formerly Bipolaris hawaiiensis) is a plant pathogen often isolated from soil and vegetative material. However, only a few cases of opportunistic invasive infections in humans have been described.

Case

A 16-year-old female patient without comorbidities was admitted to the emergency department because of fever and chest pain. We described the first coinfection of Curvularia hawaiiensis and Mycobacterium tuberculosis necrotising pneumonia.

Discussion

Multiple infections can alter immune responses. However, immunosuppression is the most critical risk factor for infection with species of the genus Curvularia. Therefore, it is crucial to carefully examine patients with tuberculosis, as they may rarely be coinfected with unusual fungi.
Posterior paramedian approach combined with a novel inverted V-shaped surgical access for intraspinal schwannomas: a retrospective case series study
Authors: Zhai Pengfei , Wu Haiyang , Tong Linjian , Wang Yulin , Sun Zhiming
Published: May 2023

Objective

To explore the efficacy and safety of the posterior paramedian approach combined with a novel inverted V-shaped surgical access for the treatment of intraspinal schwannomas.

Methods

This study retrospectively reviewed consecutive patients who underwent surgical resection of the intraspinal schwannomas via the inverted V-shaped approach at our center between January 2016 and May 2021. Changes between the preoperative and postoperative visual analog scale (VAS) scores and neurological function Japan Orthopaedic Association (JOA) scores were assessed. Secondary outcomes such as success rate of tumor resection, operation time, blood loss, spinal stability, and disruption degree of intervertebral joints. Postoperative complications were also investigated.

Results

Of these 36 consecutive patients, there were 6 cases in the cervical spine, 2 cases at the cervical-thoracic junction, 11 cases in the thoracic spine, 4 cases at the thoracic-lumbar junction and 13 cases in the lumbar spine. The average operation time was 99 min, and the average blood loss was 95.4 mL. The tumor removal rate was 100%. Postoperative CT re-examination showed that the spinous processes were intact in all cases, the facet joint surfaces were intact in 32 cases. At the time of last follow-up, the median JOA score was 25 (9–27), which was significantly improved compared to the preoperative median JOA score of 15 (10–22) (P < 0.01). The overall excellent and good rate were 88.9 %. The median VAS score at post-surgery was 0 (0–2), which was significantly improved compared to the preoperative median VAS score of 4 (2–8) (P < 0.01). As for complications, there were no cases of cerebrospinal fluid leakage or spinal instability. Three patients who had a postoperative fever finally recovered after lumbar cistern drainage.

Conclusion

The inverted V-shaped surgical access via the posterior paramedian approach is an effective and safe method for the treatment of intraspinal schwannomas.
Multivariate analysis and model building for classifying patients in the peroxisomal disorders X-linked adrenoleukodystrophy and Zellweger syndrome in Chinese pediatric patients
Authors: Zhu Zhixing , Genchev Georgi Z. , Wang Yanmin , Ji Wei , Zhang Xiaofen , Lu Hui , Sriswasdi Sira , Tian Guoli
Published: May 2023

Background

The peroxisome is a ubiquitous single membrane-enclosed organelle with an important metabolic role. Peroxisomal disorders represent a class of medical conditions caused by deficiencies in peroxisome function and are segmented into enzyme-and-transporter defects (defects in single peroxisomal proteins) and peroxisome biogenesis disorders (defects in the peroxin proteins, critical for normal peroxisome assembly and biogenesis). In this study, we employed multivariate supervised and non-supervised statistical methods and utilized mass spectrometry data of neurological patients, peroxisomal disorder patients (X-linked adrenoleukodystrophy and Zellweger syndrome), and healthy controls to analyze the role of common metabolites in peroxisomal disorders, to develop and refine a classification models of X-linked adrenoleukodystrophy and Zellweger syndrome, and to explore analytes with utility in rapid screening and diagnostics.

Results

T-SNE, PCA, and (sparse) PLS-DA, operated on mass spectrometry data of patients and healthy controls were utilized in this study. The performance of exploratory PLS-DA models was assessed to determine a suitable number of latent components and variables to retain for sparse PLS-DA models. Reduced-features (sparse) PLS-DA models achieved excellent classification performance of X-linked adrenoleukodystrophy and Zellweger syndrome patients.

Conclusions

Our study demonstrated metabolic differences between healthy controls, neurological patients, and peroxisomal disorder (X-linked adrenoleukodystrophy and Zellweger syndrome) patients, refined classification models and showed the potential utility of hexacosanoylcarnitine (C26:0-carnitine) as a screening analyte for Chinese patients in the context of a multivariate discriminant model predictive of peroxisomal disorders.
A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review
Authors: Maccora Ilaria , Maniscalco Valerio , Campani Silvia , Carrera Simona , Abbati Giulia , Marrani Edoardo , Mastrolia Maria Vincenza , Simonini Gabriele
Published: May 2023

Introduction

Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally described as mimicker of polyarteritis nodosa, with immunodeficiency and early-onset stroke.

Methods

A systematic review according to PRISMA approach, including all articles published before the 31st of August 2021 in Pubmed and EMBASE database was performed.

Results

The search identified 90 publications describing 378 unique patients (55.8% male). To date 95unique mutations have been reported. The mean age at disease onset was 92.15 months (range 0–720 months), 32 (8.5%) showed an onset of the first signs/symptoms after 18 years old and 96 (25.4%) after 10 years old. The most frequent clinical characteristics described were cutaneous (67.9%), haematological manifestations (56.3%), recurrent fever (51.3%), neurological as stroke and polyneuropathy (51%), immunological abnormalities (42.3%), arthralgia/arthritis (35.4%), splenomegaly (30.6%), abdominal involvement (29.8%), hepatomegaly (23.5%), recurrent infections (18.5%), myalgia (17.9%), kidney involvement (17.7%) etc. Patients with skin manifestations were older than the others (101.1 months SD ± 116.5, vs. 75.3 SD ± 88.2, p 0.041), while those with a haematological involvement (64.1 months SD ± 75.6 vs. 133.1 SD ± 133.1, p < 0.001) and immunological involvement (73.03 months SD ± 96.9 vs. 103.2 SD ± 112.9, p 0.05) are younger than the others. We observed different correlations among the different clinical manifestations. The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) has improved the current history of the disease.

Conclusion

Due to this highly variable phenotype and age of presentation, patients with DADA2 may present to several type of specialists. Given the important morbidity and mortality, early diagnosis and treatment are mandatory.