bluuebunny/crossref_metadata_2025 huggingface dataset:
Nail Lichen Striatus and Its Differential Diagnoses
Authors: Bilgic Aslı
Published: July 2024

Background: Lichen striatus (LS) is a benign, mostly self-limiting dermatological condition, primarily affecting the skin, and sometimes the nails. It is characterised by the sudden onset of a band-like rash, typically following Blaschko lines. The exact cause of LS is not well established, but it is believed to be an abnormal immune response to the altered keratinocyte clone after a triggering event. Summary: Although nail LS is regarded as rare, it is probably underreported. Single-visualised nail dystrophy, especially partial involvement of the nail, with or without skin rash, should prompt the LS diagnosis among differentials. Onychoscopy might be helpful to better visualise the clinical signs. Nail dystrophy often has a prolonged course even after the resolution of skin lesions. Topical steroids, calcineurin inhibitors, and intralesional steroid injections might be an option for symptomatic patients or for severe and prolonged nail dystrophy. Key Messages: (i) Single nail involvement, nail changes located on one portion of the nail, and the presence of typical linear band-like skin rash should prompt the LS diagnosis. (ii) Onychoscopy might be helpful to better visualise the clinical signs and to avoid unnecessary biopsies. (iii) Nail unit biopsy should be performed if the diagnosis is uncertain to exclude nail involvement of more severe and progressive disease course like nail lichen planus and/or nail unit tumours.
Tachycardia and Acute Kidney Injury among Critically Ill Patients with Sepsis: A Prospective Observational Study
Authors: Hayase Naoki , Yamamoto Miyuki , Asada Toshifumi , Isshiki Rei , Doi Kent
Published: July 2024

Introduction: Tachycardia caused by sympathetic overactivity impairs myocardial function and raises septic patients’ mortality. This study examined whether tachycardia is associated with acute kidney injury (AKI) period-prevalence among critically ill patients with and without sepsis. Methods: In 328 patients (119 sepsis and 209 non-sepsis) admitted to our intensive care unit (ICU), we assessed heart rate at ICU admission, plasma neutrophil gelatinase-associated lipocalin (NGAL) and N-terminal pro-B-type natriuretic peptide, and urinary L-type fatty acid-binding protein and N-acetyl-β-d-glucosaminidase (NAG) at 0 and 48 h after admission. Tachycardia was defined as a heart rate above 100 beats/min. Results: Tachycardia was independently correlated with AKI prevalence during the first week after ICU admission in the septic patients, but not in the non-septic patients. A dose-dependent increase in AKI period-prevalence was observed across ascending heart rate ranges. Furthermore, we discovered a dose-dependent increase in renal biomarker-positive patients regarding plasma NGAL and urinary NAG over increasing heart rate ranges 48 h after admission. Conclusion: The findings revealed an independent relationship between tachycardia and AKI prevalence during the first week of ICU in septic patients. Heart rate was found to have a dose-dependent effect on AKI prevalence and renal insult monitored by biomarkers.
Ex vivo Study of Partial Bladder Resection in a Porcine Model
Authors: Kielbik Aleksander , Hoffmans Timo , Amend Bastian , Stenzl Arnulf , Maas Moritz , Rausch Steffen , Kruck Stephan , Tsaur Igor , Aufderklamm Stefan
Published: July 2024

Introduction: Partial cystectomy aims to preserve bladder function, yet its urodynamic impacts remain unclear. We investigate these effects using an ex vivo porcine model, evaluating bladder volume, compliance, and wall thickness, alongside with thermal damage after bi- and monopolar resection. Methods: Within an artificial human pelvis, we conducted partial bladder wall resections (5 cm2, 10 cm2). Urodynamic tests and sonography assessed volume, compliance, and thickness changes. Traction force for catheter retrieval and thermal collagen destruction were measured. Results: Bladder compliance decreased by 1.12 and 1.5 after 5 cm2 and 10 cm2 resections, respectively, with volume reductions of 3–6% and 10–18%. Wall thickness decreased by 20% and 30% post-resection. Comparable thermal damage was observed with mono- and bipolar resection methods. Conclusion: Our study outlines urodynamic impacts and technical considerations of partial cystectomy, affirming its endoscopic feasibility while highlighting potential bladder dysfunction risks.
A Novel c.459_460insC Variation in the XK Gene Associated with McLeod Syndrome
Authors: Zhang Bing , Yu Shifang , Hong Xiaozhen , Xu Xianguo , Zhu Faming
Published: July 2024

Introduction: McLeod syndrome (MLS) is a rare X-linked recessive disorder affecting multiple systems. Herein, we present the clinical symptoms, laboratory diagnostic results, and genetic characteristics of a patient with MLS caused by a novel c.459_460insC variation in the XK gene. Case Presentation: A 58-year-old male Chinese patient presented with neurological symptoms, seeking belated medical attention at the hospital. Numerous laboratory tests indicated a high likelihood of MLS, featuring chronic granulomatosis and neuroacanthocytosis. The patient’s blood samples were sent to the Blood Center of Zhejiang Province, China, for further analysis. Sequencing analysis revealed a novel hemizygous c.459_460insC variation in exon 2 of the XK gene. Therefore, we identified a patient with MLS possessing a novel genetic variation (GenBank Accession No. OQ473658). Conclusion: Our findings elucidate a novel c.459_460insC variation associated with MLS, resulting in a frameshift and premature stop codon (p.Leu154Profs*45). The clinical manifestations, laboratory examination, and XK gene analysis in this case will aid in diagnosing MLS in future patients.
Analysis of Magnetic Resonance Imaging in Paranasal Mucocele with Visual Disturbance
Authors: Yoshida Haruo , Tanaka Fujinobu , So Kenji , Kumai Yoshihiko
Published: July 2024

Introduction: Ocular imaging strategies have evolved to facilitate the diagnosis of optic neuropathy. This study aimed to evaluate the pathogenesis of visual disturbance associated with paranasal mucocele via magnetic resonance imaging (MRI). Methods: A total of 19 patients with mucocele and visual disturbance who underwent endoscopic sinus surgery, orbital MRI, and sinus computed tomography were included. The age, sex, days from onset to surgery, eye pain, and imaging findings were analyzed. The results were compared between two groups: 7 patients with preoperative visual acuity worse than 20/200 (the poor group) and 12 patients with equal or better than 20/200 (the fair group). Results: Imaging showed a high compression rate of the orbit in 17 (89.5%) and enlargement of the subarachnoid space around the optic nerve in 15 (78.9%) of 19 patients. Preoperative vision was significantly poor in cases with hyperintense regions in the optic nerve on T2-weighted imaging, indicating the presence of optic neuritis. No cases showed severe inflammation of the cyst or the presence of intraorbital fat tissue. Conclusion: MRI-based diagnosis proved useful in evaluating pathological factors, such as orbital compression, ischemia, and optic neuritis, in individual cases. It can help in gaining insight into the pathogenesis and developing appropriate treatment strategies for visual disturbances associated with paranasal mucocele.
The Effect of Co-Morbid Psoriasis Diagnosis on Chronic Rhinosinusitis Immunopathology
Authors: Smith Aaron D. , Lyons Catherine E. , Patrie James T. , Borish Larry
Published: July 2024

Introduction: Psoriasis is a papulosquamous condition characterized by type 1 (T1) inflammation, while chronic rhinosinusitis (CRS) concurrent with asthma is commonly a type 2 (T2) process. Since psoriasis is predictive for higher rates of CRS, our objective was to determine whether CRS with concurrent psoriasis would share its T1 pathogenic signature. In comparison to T1 CRS, a T2 process can be predicted by presence of more extensive sinus disease via Lund-MacKay score, reduced sense of smell, and greater concurrence of purulent drainage and pain/pressure. Methods: Subjective measurements of CRS included the Sino-Nasal Outcome Test (SNOT-22) and objective measurements included Lund-MacKay sinus CT score and endoscopic scoring. Outcomes were compared with control subjects with CRS co-presenting with allergies, asthma, or aspirin-exacerbated respiratory disease (AERD). Results: A total of 62 patients (12 CRS alone, 14 CRS/psoriasis, 12 CRS/AERD, 12 CRS/allergic asthmatic, 12 CRS/non-allergic asthmatic) were included. Comparative analysis utilizing χ2 revealed no significant differences in any factor between CRS/psoriatic patients and all other groups associated with T2 presentations. Specifically, psoriatic patients had comparable reductions in smell, similar complaints of pain/pressure, negligible purulent drainage/crusting, and comparable extent of disease on their CT scan, as well as similar blood eosinophilia. The only significant difference was in lack of productivity (p < 0.05) with trends toward reduced concentration, waking up tired, and lack of sleep parameters presumably related to systemic psoriatic manifestations. Conclusions: Despite the increased prevalence of CRS in psoriasis patients, our data suggest that when present, psoriasis does not predict the presence of a T1 process in the sinuses.
A Population-Based and Propensity Score-Matched Investigation of the Occurrence, Management, and Prognosis of Anal Mucinous Adenocarcinoma Patients
Authors: Yao Guorong , Zhou Ziyang , Wang Yiqi , Jiang Yanting , Wang Jili , Yan Senxiang , Zhao Feng
Published: July 2024

Introduction: Anal mucinous adenocarcinoma (AMAC) is an extremely rare form of anal cancer. Our objective was to examine the incidence, management, and prognostic factors of AMAC. Methods: We analyzed age-adjusted incidence (AAI) rates over time and compared the prognosis of AMAC with anal squamous cell carcinoma (ASCC) and adenocarcinoma (AAC) using propensity score matching and Kaplan-Meier analysis. Patients were classified based on summary stage and treatments to determine cancer-specific survival. Results: AAI of AMAC fluctuated within a narrow range (0.082–0.237 per million person-years) from 2000 to 2018. AMAC had a slight non-significant trend of worse prognosis than ASCC (p = 0.348) and a better prognosis than AAC (p < 0.01). Females made up a larger proportion of patients diagnosed with the distant disease (p < 0.05) and unmarried (p < 0.05) and somewhat less probably to need surgical removal (p < 0.01) and radiotherapy (p < 0.01). Elderly patients have lower rates of survival (p < 0.05). Localized stage was associated with better prognosis (p < 0.05). Surgery was associated with a tendency toward better survival (p = 0.095). Conclusions: AMAC exhibits a low incidence yet favorable prognosis compared to typical AAC and slightly worse compared to ASCC. Elderly age is associated with poorer prognosis, while localized stage indicates better prognosis. Surgery demonstrates a trend toward improved survival.
Diagnosis and Management of Pelvic Congestion Syndrome: Comprehensive Review
Authors: Alsannan Baydaa , Alzeeny Ahmad , Etrusco Andrea , Laganà Antonio Simone , D'Amato Antonio , Tulandi Togas
Published: July 2024

Background: Pelvic congestion syndrome (PCS) is a poorly understood condition that can be associated with chronic pelvic pain and could impact quality of life. The diagnosis is often made by exclusion of other causes of pelvic pain. Objective: The purpose of our review was to provide an update on the etiology, anatomy, physiology, identification, and the therapeutic management of PCS. Method: We conducted a literature review involving publications from 2003 to 2024 in PubMed, Elsevier, MEDLINE, as well as manual searches of primary and review articles using keywords such as “pelvic veins”, “embolization”, “venography”, “pelvic congestion syndrome”, and “chronic pelvic pain”. Conclusion: PCS remains poorly understood. Symptoms can be non-specific and difficult to distinguish from other diseases; yet it is an important cause of chronic pelvic pain in women. To date, there have been only a small number of randomized trials and high-level evidence is still lacking. Outlook: We call for an increased awareness of PCS and additional clinical studies in a large number of patients.
SSc-ILD: Frau oder Mann erkrankt – macht es einen Unterschied?
Authors: Polke Markus
Published: July 2024

Objective: Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc) patients. We aimed to investigate the impact of sex on SSc-ILD. Methods: EUSTAR SSc patients with radiologically confirmed ILD and available percentage predicted forced vital capacity (%pFVC) were included. Demographics and disease features were recorded. A change in %pFVC over 12 months (S.D. 6) (cohort 1) was classified into stable (≤4%), mild (5–9%) and large progression (≥10%). In those with 2-year longitudinal %pFVC (cohort 2), the %pFVC change at each 12-month (S.D. 6) interval was calculated. Logistic regression analyses [odds ratio (OR) and 95% CI] and Cox proportional hazards models adjusted for age and %pFVC were applied. Results: A total of 1136 male and 5253 female SSc-ILD patients were identified. Males were significantly younger, had a shorter disease duration, had a higher prevalence of CRP elevation and frequently had diffuse cutaneous involvement. In cohort 1 (1655 females and 390 males), a higher percentage of males had stable ILD (74.4% vs 69.4%, P = 0.056). In multivariable analysis, disease duration and %pFVC [OR 0.99 (95% CI 0.98, 0.99) and OR 0.97 (95% CI 0.95, 0.99), respectively] in males and age, %pFVC and anti-centromere [OR 1.02 (95% CI 1.00, 1.04), OR 0.97 (95% CI 0.96, 0.98) and OR 0.39 (95% CI 0.245, 0.63), respectively] in females were associated with large progression. The 1-year mortality rate was higher in males (5.1% vs 2.5%, P = 0.013). In cohort 2 (849 females and 209 males), a higher percentage of females showed periods of large progression (11.7% vs 7.7%, P = 0.023), the percentage of patients with none, one or two periods of worsening was not different. The overall death rate was 30.9% for males and 20.4% in females (P < 0.001). In the survival analysis, male sex was a predictor of mortality [OR 1.95 (95% CI 1.66, 2.28)].
Comparison of Postoperative Axial Rotation of the Toric Intraocular Lens in Cataract Surgery Combined with Vitrectomy versus Cataract Surgery Alone
Authors: Mito Tsuyoshi , Ishida Hidetoshi , Seki Yusuke , Shirayama Takuro , Ukai Yuki , Sasaki Hiroshi
Published: July 2024

Introduction: This study compared the postoperative axial rotation of the toric intraocular lens (T-IOL) after cataract surgery combined with vitrectomy versus cataract surgery alone. Methods: This retrospective, non-randomized, observational study enrolled patients who underwent cataract surgery combined with vitrectomy in one eye and cataract surgery alone in the contralateral eye. AcrySof Toric IOLs (Alcon Laboratories) were implanted in both eyes of the same patient. The axial rotation of the T-IOL was analyzed 3 months postoperatively using photographs obtained during and after surgery. In the combined group, T-IOL axial alignment was performed before vitrectomy. Preoperative corneal astigmatism and postoperative residual astigmatism were also compared in both groups. Results: This study examined 36 eyes of 18 patients (74.7 ± 6.8 years). The axial rotation was 2.94 ± 1.70° in the cataract group versus 3.06 ± 2.34° in the combined group 3 months postoperatively, and the difference lacked significance (p = 0.98). In the combined group, the mean axial rotation during surgery was 2.17 ± 1.80°. Axial rotation within 5° was observed in 17 of 18 eyes (94.4%) in the cataract group and 16 of 18 eyes (88.9%) in the combined group, with no significant difference (p = 0.54). The comparison of postoperative residual astigmatism with preoperative corneal astigmatism revealed a significant improvement from 1.49 ± 0.40 D to 0.39 ± 0.47 D in the cataract group (p < 0.0001) and from 1.61 ± 0.40 D to 0.42 ± 0.43 D in the combined group (p < 0.0001). Conclusions: The postoperative axial rotation of the T-IOL in eyes that underwent cataract surgery combined with vitrectomy was stable and comparable to that of eyes that underwent cataract surgery alone.
A Case Report of Metastatic Gastric Cancer Treated with Pembrolizumab during Pregnancy
Authors: Piemonti Linda , Vettor Laura , Contro Elena
Published: July 2024

Introduction: Immune checkpoint inhibitors are extensively used in present-day clinical practice for treating many types of cancers at different stages. To date, there are scarce data on the use of immunotherapy in pregnancy. Immune-related adverse events are a typical consequence of this therapy miming autoimmune diseases. Case Presentation: A 35-year-old woman (G1P0) diagnosed with gastric carcinoma underwent neoadjuvant chemotherapy followed by surgery. During follow-up, axillary metastasis was discovered, radiotherapy failed, and consequently immunotherapy was started. Concurrently, pregnancy ensued. Despite potential risks, the patient opted to continue immunotherapy and the pregnancy. At 31 weeks, fetal bowel dilation was noted. Subsequently, the fetus also developed fetal growth restriction. A cesarean section was performed at 35 weeks. The newborn required repeated bowel resections for necrotizing enterocolitis, necessitating extensive medical intervention. The mother continues pembrolizumab treatment with a positive response. Conclusion: To the best of our knowledge, this might constitute a possible case of a fetal immune-related adverse event after immunotherapy in utero exposure.
Whole Exome Sequencing Indicating GGCCTG Hexanucleotide Repeat in Patients with Spinocerebellar Ataxia Type 36
Authors: Chen Ran , Zhou Chao , Peng Yun , Huang Pengcheng , Yu Yanyan , Zhu Min , Zhou Meihong , Hong Daojun , Tan Dandan
Published: July 2024

Introduction: Spinocerebellar ataxia type 36 (SCA36) is caused by large GGCCTG repeat expansion in the NOP56 gene. The genetic diagnosis based on Southern blot is expensive and time-consuming. This study aimed to evaluate the reliability and effectiveness of whole exome sequencing (WES) for routine genetic diagnosis of suspected SCA36 patients. Methods: Pathogenic repeat expansions for SCAs including SCA36 were first analyzed based on WES data using ExpansionHunter in five probands from SCA families, then the results were confirmed by triplet repeat primed polymerase chain reaction (TP-PCR) and Southern blot. Results: GGCCTG repeat expansion in NOP56 was indicated in all five probands by WES, then it was found in 11 SCA patients and three asymptomatic individuals by TP-PCR. The sizes of GGCCTG repeat expansions were confirmed to be 1,390–1,556 by Southern blot. The mean age at onset of the patients was 51.0 ± 9.3 (ranging from 41 to 71), and they presented slowly progressive cerebellar ataxia, atrophy and fasciculation in tongue or limb muscles. Conclusion: The patients were clinically and genetically diagnosed as SCA36. This study proposed that WES could be a rapid, reliable, and cost-effective routine test for the preliminarily detection of SCA36 and other ataxia diseases.
Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage
Authors: Li Mengyue , Li Tongtong , Yang Tong , Huang Ling , Zhao Jiangang , Liu Huan , Chen Yongjie , Li Wen , Zhu Yun , Ma Fei , Yan Jing , Huang Guowei
Published: July 2024

Introduction: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). Methods: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA + DHA (FA 800 μg/d + DHA 800 mg/d), FA (800 μg/d), DHA (800 mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. Results: During the 12-month follow-up, scores of full intelligence quotient (βDHA: 1.302, 95% CI: 0.615, 1.990, p < 0.001; βFA: 1.992, 95% CI: 1.304, 2.679, p < 0.001; βFA+DHA: 2.777, 95% CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA + DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA, and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). Conclusions: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone.
Low-Grade Adenosquamous Carcinoma of the Breast Masquerading as a Fibroepithelial Lesion on Core Biopsy: A Challenging Case
Authors: Laokulrath Natthawadee , Chuwa Esther , Gudi Mihir , Tan Puay Hoon
Published: July 2024

Introduction: Diagnosing low-grade adenosquamous carcinoma (LGASC) presents significant challenges due to its subtle morphology, variable immunohistochemical expression, and resemblance to benign lesions like radial scar and complex sclerosing lesions. Case Presentation: We present a case of a 53-year-old woman with a subareolar mass initially thought to be a fibroepithelial neoplasm on core biopsy. Subsequent wide excision revealed LGASC with oestrogen receptor expression (weak to moderate intensity, 40% of tumour cells). Conclusion: These findings, rarely reported, highlight the difficulty of diagnosing LGASC on small tissue samples.
Seasonal Variations in Stroke Occurrence
Authors: Brissette Vincent , Kapral Moira K. , Yu Bing , Fang Jiming , Odugbemi Tomi , Shamy Michel , Fahed Robert , Dowlatshahi Dar , Gocan Sophia , Martineau Isabelle
Published: July 2024

Background: Understanding seasonal variations in stroke can help stakeholders identify underlying causes in seasonal trends, and tailor resources appropriately to times of highest needs. We sought to evaluate the seasonal occurrence of stroke and its subtypes. Methods: We conducted a retrospective cohort study using administrative data from January 1st, 2003, to December 31st, 2017, in Ontario, Canada’s most populous province. We evaluated seasonal variations in stroke occurrence by subtype, via age/sex standardized rates and adjusted rate ratios using Poisson regressions. In those with stroke, we evaluated 30-day case fatality risks by season, adjusted for age, sex, stroke type, and comorbid conditions, and then used Cox proportional hazard models to estimate the effect of season on the fatality. The administrative data used in this study were from the Canadian Institute for Health Information’s Discharge Abstract Database, the National Ambulatory Care Reporting System Database, the Ontario Registered Persons Database, and the 2006 and 2011 Canada Census and linked administrative databases. Results: During our study period, we observed 394,145 strokes or TIA events, with a decrease in monthly hospitalization/emergency department visits per 100,000 people between January 2003 and December 2017 from 24.22 to 17.43. Compared to the summer, overall stroke occurrence was similar in the spring but slightly lower in the fall (adjusted rate ratio [aRR] 0.97, 95% confidence interval [CI] 0.96–0.98) and winter (aRR 0.94, 95% CI: 0.94–0.95). There were minor variations by stroke subtype. Winter was associated with the highest risk of stroke case fatality compared to the summer (12.4% vs. 11.4%, adjusted hazard ratio 1.10, 95% CI: 1.07–1.13). Conclusions: We found seasonal variations in stroke occurrence and case fatality, although the absolute differences were small. Further work is needed to better understand how environmental or meteorological factors might affect stroke risk.
Phosphodiesterase-5 Inhibitors and Dementia Risk: A Real-World Study
Authors: Gronich Naomi , Stein Nili , Saliba Walid
Published: July 2024

Introduction: Biological and scarce epidemiological evidence suggested that phosphodiesterase-5 inhibitors (PDE5i) might reduce dementia risk. We aimed to examine the association between PDE5i and dementia using real-world data. Methods: Two retrospective cohorts within the database of Clalit, the largest healthcare provider in Israel (2005–2023), were studied. The first cohort included new daily users, older than 50 years of age, of low-dose tadalafil, prescribed for benign prostatic hypertrophy (BPH), propensity-score matched to new-users of alpha-1 blockers, and analyzed using 2-year lag time. The second cohort included patients with erectile dysfunction, with/without any PDE5i treatment, using time-dependent analysis. Individuals in the cohorts were followed through May 2023 for the occurrence of dementia. Results: The first cohort included 5,204 tadalafil initiators propensity-score matched to 18,565 alpha-1 blockers initiators. There was no association between tadalafil use and dementia risk, HR = 0.99 (95% CI: 0.88–1.12), p = 0.927. Similar results were obtained in a competing risk analysis, and in a sensitivity analysis in which we restricted the cohort to patients older than 60 years at cohort entry. The second cohort of 133,336 patients with erectile dysfunction included new users and nonusers of any PDE5i. In a mean follow-up of 7.9 years, 8,631 patients were newly diagnosed with dementia. In a time-dependent multivariable analysis, PDE5i use was not associated with reduced dementia risk, HR = 0.95 (95% CI: 0.86–1.04). Results were not changed in sensitivity analyses (patients older than 60 years or stratification by PDE5i type). Conclusion: This study suggests that the use of PDE5 inhibitors is not associated with decreased risk of dementia.
Salivary Proteins and Metabolites as Caries Biomarkers in Adolescents
Authors: Havsed Kristian , Carda-Diéguez Miguel , Isaksson Helen , Stensson Malin , Carlsson Emma , Jansson Henrik , Malmodin Daniel , Nord Anders Bay , Wickström Claes , Mira Alex
Published: July 2024

Introduction: The identification of salivary molecules that can be associated to dental caries could provide insights about caries risk and offer valuable information to develop caries prediction models. However, the search for a universal caries biomarker has proven elusive due to the multifactorial nature of this oral disease. We have therefore performed a systematic effort to identify caries-associated metabolites and proteins in saliva samples from adolescents that had a caries experience and those that were caries-free. Methods: Quantification of approximately 100 molecules was performed by the use of a wide range of techniques, ranging from nuclear magnetic resonance metabolomics to ELISA, Luminex or colorimetric assays, as well as clinical features like plaque accumulation and gingival index. In addition, simplified dietary and oral hygiene habits questionnaires were also obtained. Results: The caries-free group had significantly lower consumption of sweetened beverages and higher tooth brushing frequency. Surprisingly, very few compounds were found to individually provide discriminatory power between caries-experienced and caries-free individuals. The data analysis revealed several potential reasons that could underly this lack of association value with caries, including differences in metabolite concentrations throughout the day, a lack of correlation between metabolite concentrations in plaque and saliva, or sex-related differences, among others. However, when multiple compounds were combined by multivariate analysis and random forest modeling, a combination of 3–5 compounds were found to provide good prediction models for morning (with an AUC accuracy of 0.87) and especially afternoon samples (AUC = 0.93). Conclusion: While few salivary biomarkers could differentiate between caries-free and caries-experienced adolescents, a combination of markers proved effective, particularly in afternoon samples. To predict caries risk, these biomarkers should be validated in larger cohorts and longitudinal settings, considering factors such as gender differences, and variations in oral hygiene and diet.
Perihaematomal Oedema Evolution over 2 Weeks after Spontaneous Intracerebral Haemorrhage and Association with Outcome: A Prospective Cohort Study
Authors: Samarasekera Neshika , Ferguson Karen , Parry-Jones Adrian Robert , Rodrigues Mark , Loan James , Moullaali Tom J. , Hughes Jeremy , Shoveller Laura , Wardlaw Joanna , McColl Barry , Allan Stuart M. , Selim Magdy , Norrie John , Smith Colin , Al-Shahi Salman Rustam
Published: July 2024

Introduction: We know little about the evolution of perihaematomal oedema (PHO) >24 h after ICH onset. We aimed to determine the trajectory of PHO after ICH onset and its association with outcome. Methods: We did a prospective cohort study using a pre-specified scanning protocol in adults with first-ever spontaneous ICH and measured absolute PHO volumes on CT head scans at ICH diagnosis and 3 ± 2, 7 ± 2, and 14 ± 2 days after ICH onset. We used the largest ICH if ICHs were multiple. The primary outcomes were (a) the trajectory of PHO after ICH onset and (b) the association between PHO (absolute volume at the time when most repeat CT head scans were obtained, and change in PHO volume at this time compared with the first CT head scan) and poor functional outcome (modified Rankin scale 3–6 at 90 days). We pre-specified multivariable logistic regression models of this association adjusting analyses for potential confounders: age, GCS, infratentorial ICH location, and intraventricular extension. Results: In 106 participants of whom 49 (46%) were female, with a median ICH volume 7 mL (interquartile range [IQR] 2–22 mL), the trajectory of median PHO volume increased from 14 mL (IQR: 7–26 mL) at diagnosis to 18 mL (IQR: 8–40 mL) at 3 ± 2 days (n = 87), 20 mL (IQR: 8–48 mL) at 7 ± 2 days (n = 93) and 21 mL (IQR: 10–54 mL) at 14 ± 2 days (n = 78) (p = <0.001). PHO volume at each time point was collinear with ICH volume at diagnosis (│r│ >0.7), but the change in PHO volume between diagnosis and each time point was not. Given collinearity, we used total lesion (i.e., ICH + PHO) volume instead of PHO volume in a logistic regression model of its association at each time point with outcome. Increasing total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome (adjusted OR per mL 1.02, 95% CI: 1.00–1.03; p = 0.036), but the increase in PHO volume between diagnosis and day 7 ± 2 was not associated with poor functional outcome (adjusted OR per mL 1.03, 95% CI: 0.99–1.07; p = 0.132). Conclusion: PHO volume increases throughout the first 2 weeks after onset of mild to moderate ICH. Total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome, but the change in PHO volume between diagnosis and day 7 ± 2 was not. Prospective cohort studies with larger sample sizes are needed to investigate these associations and their modifiers.
Biological Effects of New Chemical-Mechanical Caries Removal Products on Human Dental Pulp Stem Cells
Authors: López-García Sergio , Pérez-Guzmán Nuria , Rodríguez-Lozano Francisco J. , Pecci-Lloret María Pilar , García-Bernal David , Murcia Laura , Oñate-Sánchez Ricardo E. , Llena Carmen
Published: July 2024

Introduction: The aim of this study was to compare the biological effects of four chemical caries removal materials and to assess their cytotoxicity using human dental pulp stem cells (hDPSCs). Methods: The products evaluated are: 1 – papain-based product (BRIX 3000®); 2 – papain/chloramine based products (NATURAL-CARE and Papacárie Duo®); and 3 – chloramine based product (Cariesolut). The following in vitro experiments were carried out: IC50 measurement, cell metabolic activity (MTT) assay, cell migration, immunofluorescence experiment, cell apoptosis analysis, and reactive oxygen species (ROS) production analysis. Statistical analyses were performed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05). Results: The IC50 values were: Brix 3000: 0.596%; Papacárie Duo: 0.052%; NATURAL CARE: 1.034%; and Cariesolut: 0.020%. The MTT assays showed non-adequate cell viability of all chemical-mechanical caries removal tested at 2% at 24, 48, and 72 h (p < 0.001). The same behaviour was observed at 0.1% in the Papacárie Duo and Cariesolut groups. In contrast, 0.1% of Brix 3000 at all times and NATURAL CARE at 24 h treated cells showed cell viability rates similar to the control group. At 0.01% only Brix 3000 did not show statistically significant differences at any time. Delayed cell migration was observed in all hDPSCs treated with Papacárie Duo and Cariesolut (p < 0.01 and p < 0.001). Phalloidin staining images showed a high confluence of cells in the presence of NATURAL CARE, similar to the control group. On the contrary, no cells were observed in Brix 3000 and Cariesolut at 2% and 0.1% concentrations. Papacárie Duo showed cells at all concentrations, but hDPSCs treated at 0.01% concentration exhibited better proliferation and spreading than those in the control group. Apoptosis essay showed that Brix 3000 at both 0.1% and 0.01% had a percentage of live cells higher than 99%, with 68.4% live cells at 2%, 3.69% early apoptotic cells, and 27.9% late apoptotic cells. Conversely, the rest of the materials showed an abundance of apoptotic cells, even at low concentrations. 0.1% and 0.01% of BRIX 3000 did not affect the ROS production levels, while 2% of BRIX 3000 counterpart very significantly increased the percentage of CM-H2DCFDA positive cells. Again, all concentrations of Cariesolut showed significantly higher levels of ROS production than those observed in control cells. Conclusion: Our results suggest that Brix 3000 would be the most suitable material for chemical caries removal, with Papacárie Duo and NATURAL CARE also being good options, and discourage the use of Cariesolut due to its low cytocompatibility on dental pulp stem cells.
Systematic Evaluation of Hematoma Expansion Models in Spontaneous Intracerebral Hemorrhage: A Meta-Analysis and Meta-Regression Approach
Authors: Wu Ruoru , Hong Tao , Li Ye
Published: July 2024

Introduction: Accurate prediction of hematoma expansion (HE) in spontaneous intracerebral hemorrhage (sICH) is crucial for tailoring patient-specific treatments and improving outcomes. Recent advancements have yielded numerous HE risk factors and predictive models. This study aims to evaluate the characteristics and efficacy of existing HE prediction models, offering insights for performance enhancement. Methods: A comprehensive search was conducted in PubMed for observational studies and randomized controlled trials focusing on HE prediction, written in English. The prediction models were categorized based on their incorporated features and modeling methodology. Rigorous quality and bias assessments were performed. A meta-analysis of studies reporting C-statistics was executed to assess and compare the performance of current HE prediction models. Meta-regression was utilized to explore heterogeneity sources. Results: From 358 initial records, 22 studies were deemed eligible, encompassing traditional models, hematoma imaging feature models, and models based on artificial intelligence or radiomics. Meta-analysis of 11 studies, involving 12,087 sICH patients, revealed an aggregated C-statistic of 0.74 (95% CI: 0.69–0.78) across seven HE prediction models. Eight characteristics related to development cohorts were identified as key factors contributing to performance variability among these models. Conclusion: The findings indicate that the current predictive capacity for HE risk remains suboptimal. Enhanced accuracy in HE prediction is vital for effectively targeting patient populations most likely to benefit from tailored treatment strategies.
The Revised Reflux Symptom Index (R-RSI): Development, Internal and External Validation Study
Authors: Nacci Andrea , de Bortoli Nicola , Capobianco Silvia , Simoni Federica , Giusti Tamanai , Visaggi Pierfrancesco , Barillari Maria Rosaria , Savarino Edoardo Vincenzo , Frazzoni Marzio , Berrettini Stefano , Fattori Bruno , Bastiani Luca
Published: July 2024

Introduction: This study proposes a revised version of the Reflux Symptom Index (R-RSI), a seventeen-item questionnaire that was revised to increase the suspicion of laryngopharyngeal reflux disease (LPRD). Methods: Internal validation involved 213 participants, comprising 160 subjects without a previous LPRD diagnosis and 53 subjects with a self-reported previous diagnosis of LPRD with or without gastroesophageal reflux disease (GERD). Test-retest reliability and internal consistency were calculated. For the external validation, 56 patients (independent from the previous cohort) were enrolled to explore the R-RSI screening properties and determine a cutoff using 24-h MII-pH as the gold standard. Results: R-RSI test-retest reliability was high, both for the total score (ICC: 0.970) and for each item (ranging from 0.876 to 0.980). Cronbach’s alpha was 0.910, indicating excellent internal consistency of the questionnaire. Participants with a previous self-reported diagnosis scored significantly higher (mean 24.94 ± 7.4; median 26, IQR 20–29) than those without a previous diagnosis (mean 4.66 ± 5.3; median 4, IQR 1–6) (p value <0.0001). Participants with both previous LPRD and GERD diagnoses had higher scores (27.20 ± 7.8) compared to those with only LPRD (21.77 ± 5.5) (p value = 0.003). Using 24-h MII-pH diagnosis as a gold standard, the optimal R-RSI cutoff point was determined to be 18, with a sensitivity of 84.5% and a specificity of 81.8%, positive predictive value of 95%, and negative predictive value of 60%. Conclusions: Our results suggest that the R-RSI may be useful to suspect LPRD, with or without GERD. The R-RSI is a self-administered patient-reported outcome questionnaire that demonstrates excellent reliability and high screening properties. Employing a cutoff of ≥18 in the R-RSI can assist in diagnosing and monitoring LPRD.
Efficacy and Safety of Anti-Osteoporotic Agents Across CKD Stages:
A Meta-Analysis of Randomized Clinical Trials
Authors: Sabaghian Tahereh , Delkash Parisa , Rahmannia Maryam , Shahidi Bonjar Amir Hashem , Centis Rosella , D’Ambrosio Lia , Sotgiu Giovanni , Nasiri Mohammad Javad , Migliori Giovanni Battista
Published: July 2024

Introduction: Osteoporosis poses a significant health concern, especially for individuals with chronic kidney disease (CKD). CKD disrupts mineral and bone metabolism, heightening the risk of fractures and complicating the management of osteoporosis. While anti-osteoporotic interventions aim to address bone health in CKD patients, ongoing research is essential to understand the comparative efficacy and safety of these medications, particularly in different CKD stages, notably in Stages 4 and 5.

Methods: We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials assessing the efficacy and safety of osteoporosis interventions in CKD up to June 15, 2024. The analysis utilized the pooled odds ratio (OR) along with the corresponding 95% confidence interval (CI), employing Comprehensive Meta-Analysis software, version 3.0. To assess heterogeneity in the results of individual studies, we used Cochran's Q statistic and the I2 statistic.

Results: We analyzed 12 randomized controlled trials involving 31,027 participants, revealing a significantly lower risk of vertebral fractures with anti-osteoporotic agents (Teriparatide, Denosumab, Romosozumab, Raloxifene) compared to placebo (pooled OR, 0.28 [95% CI, 0.22 to 0.36]). Stratification by CKD stages showed a lower risk in Stages 1-3 but no significant reduction in Stages 4 and 5.
Teriparatide, Denosumab, and Romosozumab were effective in lowering fracture risk, whereas Raloxifene showed no significant effect.
The lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (Denosumab, Raloxifene, Risedronate, Alendronate, Teriparatide) and placebo. However, Romosozumab demonstrated a significantly greater BMD change in all kidney function categories. No reported side effects were observed in CKD stages 1 to 5 across the trials.

Conclusions: Our meta-analysis highlights the effectiveness of anti-osteoporotic agents in lowering vertebral fracture risk in CKD patients, particularly in Stages 1-3. However, this benefit is not apparent in Stages 4 and 5, necessitating further research. Despite the absence of reported side effects in CKD patients, clinicians should carefully assess the suitability of these medications, considering individual risks and benefits.
Advancements in myopic macular foveoschisis research
Authors: Chen He , Liu Xuan , Zhou Xuebin , Fu Jinling , Wang Lufei
Published: July 2024

In recent years, macular foveoschisis has emerged as a prevalent complication in individuals with high myopia, primarily resulting from the synergistic effect of inward traction by vitreoretinal adhesions and outward traction exerted by posterior scleral staphyloma on the retina. While some maintain partial visual stability over an extended period, others may progress to macular holes or even retinal detachment. The primary surgical interventions include vitrectomy, macular buckling, and posterior scleral reinforcement. However, the application of inner limiting membrane peeling and gas tamponade remains a subject of ongoing debate concerning their necessity and efficacy. This review comprehensively addresses the classification, pathogenesis, natural progression, concomitant pathologies, and therapeutic strategies for macular foveoschisis in highly myopic patients.
A de novo PRPF8 Pathogenic Variant in Transient Severe Hypophosphatemia with Delayed Puberty and Growth Failure
Authors: Koljonen Laura , Salonen Pia , Rusanen Salla , Mäyränpää Mervi K. , Pekkinen Minna , Mäkitie Outi
Published: July 2024

Introduction: Childhood hypophosphatemia is a rare condition and may be caused by malabsorption, malignancies, or genetic factors. Prolonged hypophosphatemia leads to impaired growth and radiographic signs of rickets. Methods: We performed a detailed clinical and genetic evaluation of an adolescent boy with repeatedly low plasma phosphate concentrations (below 0.60 mmol/L) and growth failure. Results: At 14 years, the patient presented with decelerating growth and delayed puberty. Biochemistry showed hypophosphatemia due to increased urinary phosphate loss; kidney function and vitamin D status were normal. Radiographs showed mild metaphyseal changes. A gene panel for known genetic hypophosphatemia was negative. Trio exome analysis followed by Sanger sequencing identified a pathogenic heterozygous de novo stop-gain variant in PRPF8 gene, c.5548C>T p.(Arg1850*), in the conserved RNase H homology domain. PRPF8 encodes the pre-RNA protein 8, which has a role in RNA processing. Heterozygous PRPF8 variants have been associated with retinitis pigmentosa and neurodevelopmental disorders but not with phosphate metabolism. The patient underwent growth hormone (GH) stimulation tests which confirmed GH deficiency. Head MRI indicated partially empty sella. GH treatment was started at 15 years. Surprisingly, phosphate metabolism normalized during GH treatment, suggesting that hypophosphatemia was at least partly secondary to GH deficiency. Conclusion: The evaluation of an adolescent with profound long-term hypophosphatemia revealed a pituitary developmental defect associated with a stop-gain variant in PRPF8. Hypophosphatemia alleviated with GH treatment. The pathological PRPF8 variant may contribute to abnormal pituitary development; however, its role in phosphate metabolism remains uncertain.
Analysis of Supraglottic Activity during Vocalization in Flamenco Singers
Authors: Hermoso Irene , Rodriguez Miguel , Quezada Camilo , Guzmán Marco
Published: July 2024

Introduction: Flamenco is a traditional music originally from Andalusia in southern Spain. Some of the vocal resources used in Flamenco have components of voice distortion and other voice qualities that could sound like hyperfunctional voice productions. The present study aimed at observing supraglottic activity in flamenco singers while engaged in singing at various degrees of pitch and loudness and while engaged in realizing phonatory tasks. Methods: A total of eighteen flamenco singers with at least 5 years of voice training were recruited. Flexible endoscopic voice evaluations were recorded and edited to provide samples of different pitches, loudness levels, and phonatory tasks. Sound was removed from video samples. Two blinded laryngologists were asked to assess antero-posterior compression, medial compression, pharyngeal compression, and VLP for every sample, using a visual analog scale. Results: Significantly higher values were found for medial compression, anterior-posterior compression, VLP and pharyngeal compression during high loudness levels when compared to medium and low loudness. Overall, medial compression was lower than anterior-posterior compression. Conclusion: Supraglottic activity is present in flamenco singing in the four laryngoscopic variables. It seems to be that supraglottic activity increases with loudness level and pitch. This behavior could be a natural and necessary aspect of flamenco singing present during both sustained vowels and song.
Prevalence and Risk Factors of Cerebral Microbleeds among Egyptian Patients with Acute Ischemic Stroke
Authors: Nasreldein Ahmed , Shoamnesh Ashkan , Foli Nageh , Makboul Marwa , Salah Sabreen , Faßbender Klaus , Walter Silke
Published: July 2024

Background: Cerebral microbleeds (CMBs) are markers of underlying hemorrhage-prone cerebral small vessel disease detected on MRI. They are associated with a heightened risk of stroke and cognitive decline. The prevalence of CMBs among Egyptian patients with ischemic stroke is not well studied. Our aim was to detect the prevalence of CMBs and associated risk factors among Egyptian patients with ischemic stroke. Methods: A prospective, cross-sectional, single-center study of consecutive patients with ischemic stroke. Patients were recruited between January 2021 and January 2022 at the Assiut University Hospital in the south of Egypt. Patients with known bleeding diathesis were excluded. All participants underwent full neurological assessment, urgent laboratory investigations, and MRI with T2* sequence. Results: The study included 404 patients, 191 (47.3%) of them were females. The mean age of the study population was 61 ± 1 years, and the mean NIHSS on admission was 12 ± 5. The prevalence of CMB was 26.5%, of whom 6.5% were young adults (age ≤45 years). CMBs were detected in 34.6% of patients with stroke caused by large artery atherosclerosis, 28.0% with small vessel disease stroke subtype, 25.2% with stroke of undetermined cause, and in 12.1% with cardioembolic stroke. History of AF, hypertension, dyslipidemia, Fazekas score >2, dual antiplatelet use, combined antiplatelet with anticoagulant treatment, and thrombolytic therapy remained independently associated with CMBs following multivariable regression analyses. Conclusion: The high number of identified CMBs needs to inform subsequent therapeutic management of these patients. We are unable to determine whether the association between CMBs and antithrombotic use is a causal relationship or rather confounded by indication for these treatments in our observational study. To understand more about the underlying cause of this finding, more studies are needed.