bluuebunny/crossref_metadata_2025 huggingface dataset:
Splenic Arterial Pulsatility Index to Predict Hepatic Fibrosis in Hemodialysis Patients with Chronic Hepatitis C Virus Infection
Authors: Liu Chen-Hua , Fang Yu-Jen , Liu Chun-Jen , Su Tung-Hung , Huang Shang-Chin , Tseng Tai-Chung , Wu Jo-Hsuan , Chen Pei-Jer , Kao Jia-Horng
Published: March 2023

The clinical utility of the splenic arterial pulsatility index (SAPI), a duplex Doppler ultrasonographic index, to predict the stage of hepatic fibrosis in hemodialysis patients with chronic hepatitis C virus (HCV) infection remains elusive. We conducted a retrospective, cross-sectional study to include 296 hemodialysis patients with HCV who underwent SAPI assessment and liver stiffness measurements (LSMs). The levels of SAPI were significantly associated with LSMs (Pearson correlation coefficient: 0.413, p < 0.001) and different stages of hepatic fibrosis as determined using LSMs (Spearman’s rank correlation coefficient: 0.529, p < 0.001). The areas under receiver operating characteristics (AUROCs) of SAPI to predict the severity of hepatic fibrosis were 0.730 (95% CI: 0.671–0.789) for ≥F1, 0.782 (95% CI: 0.730–0.834) for ≥F2, 0.838 (95% CI: 0.781–0.894) for ≥F3, and 0.851 (95% CI: 0.771–0.931) for F4. Furthermore, the AUROCs of SAPI were comparable to those of the fibrosis index based on four parameters (FIB-4) and superior to those of the aspartate transaminase (AST)-to-platelet ratio index (APRI). The positive predictive value (PPV) for ≥F1 was 79.5% when the Youden index was set at 1.04, and the negative predictive values (NPVs) for ≥F2, ≥F3, and F4 were 79.8%, 92,6%, and 96.9%, respectively, when the maximal Youden indices were set at 1.06, 1.19, and 1.30. The diagnostic accuracies of SAPI with the maximal Youden index for a fibrosis stage of ≥F1, ≥F2, ≥F3, and F4 were 69.6%, 67.2%, 75.0%, and 85.1%, respectively. In conclusion, SAPI can serve as a good noninvasive index in predicting the severity of hepatic fibrosis in hemodialysis patients with chronic HCV infection.
Neuroworsening in the Emergency Department Is a Predictor of Traumatic Brain Injury Intervention and Outcome: A TRACK-TBI Pilot Study
Authors: Yue John , Krishnan Nishanth , Kanter John , Deng Hansen , Okonkwo David , Puccio Ava , Madhok Debbie , Belton Patrick , Lindquist Britta , Satris Gabriela , Lee Young , Umbach Gray , Duhaime Ann-Christine , Mukherjee Pratik , Yuh Esther , Valadka Alex , DiGiorgio Anthony , Tarapore Phiroz , Huang Michael , Manley Geoffrey , Investigators The
Published: March 2023

Introduction: Neuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization. Methods: Adult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan <24 h post-injury. Neuroworsening was defined as a decline in motor GCS at ED disposition (vs. ED admission). Clinical and CT characteristics, neurosurgical intervention, in-hospital mortality, and 3- and 6-month Glasgow Outcome Scale-Extended (GOS-E) scores were compared by neuroworsening status. Multivariable regressions were performed for neurosurgical intervention and unfavorable outcome (GOS-E ≤ 3). Multivariable odds ratios (mOR) with [95% confidence intervals] were reported. Results: In 481 subjects, 91.1% had ED admission GCS 13–15 and 3.3% had neuroworsening. All neuroworsening subjects were admitted to intensive care unit (vs. non-neuroworsening: 26.2%) and were CT-positive for structural injury (vs. 45.4%). Neuroworsening was associated with subdural (75.0%/22.2%), subarachnoid (81.3%/31.2%), and intraventricular hemorrhage (18.8%/2.2%), contusion (68.8%/20.4%), midline shift (50.0%/2.6%), cisternal compression (56.3%/5.6%), and cerebral edema (68.8%/12.3%; all p < 0.001). Neuroworsening subjects had higher likelihoods of cranial surgery (56.3%/3.5%), intracranial pressure (ICP) monitoring (62.5%/2.6%), in-hospital mortality (37.5%/0.6%), and unfavorable 3- and 6-month outcome (58.3%/4.9%; 53.8%/6.2%; all p < 0.001). On multivariable analysis, neuroworsening predicted surgery (mOR = 4.65 [1.02–21.19]), ICP monitoring (mOR = 15.48 [2.92–81.85], and unfavorable 3- and 6-month outcome (mOR = 5.36 [1.13–25.36]; mOR = 5.68 [1.18–27.35]). Conclusions: Neuroworsening in the ED is an early indicator of TBI severity, and a predictor of neurosurgical intervention and unfavorable outcome. Clinicians must be vigilant in detecting neuroworsening, as affected patients are at increased risk for poor outcomes and may benefit from immediate therapeutic interventions.
How Can Machine Perfusion Change the Paradigm of Liver Transplantation for Patients with Perihilar Cholangiocarcinoma?
Authors: Patrono Damiano , Colli Fabio , Colangelo Matteo , De Stefano Nicola , Apostu Ana Lavinia , Mazza Elena , Catalano Silvia , Rizza Giorgia , Mirabella Stefano , Romagnoli Renato
Published: March 2023

Perihilar cholangiocarcinomas (pCCA) are rare yet aggressive tumors originating from the bile ducts. While surgery remains the mainstay of treatment, only a minority of patients are amenable to curative resection, and the prognosis of unresectable patients is dismal. The introduction of liver transplantation (LT) after neoadjuvant chemoradiation for unresectable pCCA in 1993 represented a major breakthrough, and it has been associated with 5-year survival rates consistently >50%. Despite these encouraging results, pCCA has remained a niche indication for LT, which is most likely due to the need for stringent candidate selection and the challenges in preoperative and surgical management. Machine perfusion (MP) has recently been reintroduced as an alternative to static cold storage to improve liver preservation from extended criteria donors. Aside from being associated with superior graft preservation, MP technology allows for the safe extension of preservation time and the testing of liver viability prior to implantation, which are characteristics that may be especially useful in the setting of LT for pCCA. This review summarizes current surgical strategies for pCCA treatment, with a focus on unmet needs that have contributed to the limited spread of LT for pCCA and how MP could be used in this setting, with a particular emphasis on the possibility of expanding the donor pool and improving transplant logistics.
Relationship of Extravascular Lung Water and Pulmonary Vascular Permeability to Respiratory Mechanics in Patients with COVID-19-Induced ARDS
Authors: Lardet Florian , Monnet Xavier , Teboul Jean-Louis , Shi Rui , Lai Christopher , Fossé Quentin , Moretto Francesca , Gobé Thibaut , Jelinski Ludwik , Combet Margot , Pavot Arthur , Guérin Laurent , Pham Tài
Published: March 2023

During acute respiratory distress syndrome (ARDS), the increase in pulmonary vascular permeability and lung water induced by pulmonary inflammation may be related to altered lung compliance. A better understanding of the interactions between respiratory mechanics variables and lung water or capillary permeability would allow a more personalized monitoring and adaptation of therapies for patients with ARDS. Therefore, our main objective was to investigate the relationship between extravascular lung water (EVLW) and/or pulmonary vascular permeability index (PVPI) and respiratory mechanic variables in patients with COVID-19-induced ARDS. This is a retrospective observational study from prospectively collected data in a cohort of 107 critically ill patients with COVID-19-induced ARDS from March 2020 to May 2021. We analyzed relationships between variables using repeated measurements correlations. We found no clinically relevant correlations between EVLW and the respiratory mechanics variables (driving pressure (correlation coefficient [CI 95%]: 0.017 [−0.064; 0.098]), plateau pressure (0.123 [0.043; 0.202]), respiratory system compliance (−0.003 [−0.084; 0.079]) or positive end-expiratory pressure (0.203 [0.126; 0.278])). Similarly, there were no relevant correlations between PVPI and these same respiratory mechanics variables (0.051 [−0.131; 0.035], 0.059 [−0.022; 0.140], 0.072 [−0.090; 0.153] and 0.22 [0.141; 0.293], respectively). In a cohort of patients with COVID-19-induced ARDS, EVLW and PVPI values are independent from respiratory system compliance and driving pressure. Optimal monitoring of these patients should combine both respiratory and TPTD variables.
Practice Patterns of Antithrombotic Therapy during the Early Postoperative Course of Cardiac Surgery
Authors: Klein Thomas , Bignolas Hugo , Mongardon Nicolas , Abou-Arab Osama , Guinot Pierre Grégoire , Bouglé Adrien , Guerci Philippe
Published: March 2023

Background: The current practices regarding the management of antithrombotic therapy during the early postoperative course of cardiac surgery are not well described. Methods: An online survey with multiple-choice questions was sent to cardiac anesthesiologists and intensivists from France. Results: The response rate was 27% (n = 149), with 2/3 of the respondents having less than 10 years of experience. A total of 83% of the respondents reported using an institutional protocol for antithrombotic management. A total of 85% (n = 123) of the respondents regularly used low-molecular-weight heparin (LMWH) during the immediate postoperative course. For 23%, 38%, 9%, and 22% of the physicians, LMWH administration was initiated between the 4th and 6th hour, between the 6th and 12th hour, between the 12th and 24th hour, and on postoperative day 1, respectively. The main reasons for not using LMWH (n = 23) were a perceived increased risk of perioperative bleeding (22%), poor reversal compared with unfractionated heparin (74%), local habits and the refusal of surgeons (57%), and its overly complex management (35%). The modalities of LMWH use were widely varied among the physicians. Chest drains were mostly removed within 3 days of surgery with an unchanged dose of antithrombotic therapy. Regarding temporary epicardial pacing wire removal anticoagulation, 54%, 30%, and 17% of the respondents left the dose unchanged, suspended the anticoagulation, or lowered the anticoagulation dose, respectively. Conclusion: LMWH was inconsistently used after cardiac surgery. Further research is warranted to provide high-quality evidence regarding the benefits and safety of LMWH use early after cardiac surgery.
COVID-19 and the Response to Antiplatelet Therapy
Authors: Bolek Tomáš , Samoš Matej , Jurica Jakub , Stančiaková Lucia , Péč Martin Jozef , Škorňová Ingrid , Galajda Peter , Staško Ján , Mokáň Marián , Kubisz Peter
Published: March 2023

The coronavirus SARS-CoV2 disease (COVID-19) is connected with significant morbidity and mortality (3.4%), disorders in hemostasis, including coagulopathy, activation of platelets, vascular injury, and changes in fibrinolysis, which may be responsible for an increased risk of thromboembolism. Many studies demonstrated relatively high rates of venous and arterial thrombosis related to COVID-19. The incidence of arterial thrombosis in severe/critically ill intensive care unit–admitted COVID-19 patients appears to be around 1%. There are several ways for the activation of platelets and coagulation that may lead to the formation of thrombi, so it is challenging to make a decision about optimal antithrombotic strategy in patients with COVID-19. This article reviews the current knowledge about the role of antiplatelet therapy in patients with COVID-19.
Epidemiological and Immune Profile Analysis of Italian Subjects with Endometriosis and Multiple Sclerosis
Authors: Zizolfi Brunella , Foreste Virginia , Bonavita Simona , Rubino Valentina , Ruggiero Giuseppina , Brescia Morra Vincenzo , Lanzillo Roberta , Carotenuto Antonio , Boscia Francesca , Taglialatela Maurizio , Guida Maurizio
Published: March 2023

Objective: To report for the first time an Italian epidemiological analysis of the prevalence of multiple sclerosis (MS) in patients with endometriosis (EMS), through the study of the endometriosis population of our referral center; to analyze the clinical profile and perform a laboratory analysis to examine the immune profile and the possible correlation to other autoimmune diseases of the enrolled patients. Methods: We evaluated 1652 women registered with EMS in the University of Naples Federico II and retrospectively searched patients with a co-diagnosis of MS. Clinical features of both conditions were recorded. Serum autoantibody and immune profiles were analyzed. Results: 9 out of 1652 patients presented a co-diagnosis of EMS and MS (9/1652 = 0.005%). Clinically, EMS and MS presented in mild forms. Hashimoto’s thyroiditis was found in two patients (2/9). Even if not statistically significant, a trend of variation in CD4- CD8 T lymphocytes and of B cells were found. Conclusion: Our findings suggest an increased risk of MS in women with EMS. However, large-scale prospective studies are needed.
Efficacy of CDK 4/6 Inhibitors and Radiotherapy in Breast Cancer Patients with Brain Metastases
Authors: Kubeczko Marcin , Jarząb Michał , Krzywon Aleksandra , Gräupner Donata , Polakiewicz-Gilowska Anna , Gabryś Dorota
Published: March 2023

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard of care for HR-positive/HER2-negative advanced breast cancer patients. However, their role in the treatment of brain metastases is currently unclear. We retrospectively evaluate the results of patients (pts) with advanced breast cancer treated at our institution with CDK4/6i and radiotherapy to the brain. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC) and severe toxicity. Among 371 pts treated with CDK4/6i, 24 pts (6.5%) received radiotherapy to the brain before (11 pts), during (6 pts), or after (7 pts) CDK4/6i treatment. Sixteen pts received ribociclib, six received palbociclib, and two received abemaciclib. Six- and twelve-month PFS was 76.5% (95% CI: 60.3–96.9) and 49.7% (95% CI: 31.7–77.9), respectively, whereas six- and twelve-month LC was 80.2% (95% CI: 58.7–100) and 68.8% (95% CI: 44.5–100), respectively. With a median follow-up of 9.5 months, no unexpected toxicity was observed. We conclude that treatment with both CDK4/6i and brain radiotherapy is feasible and should not increase the toxicity compared to brain radiotherapy or CDK4/6i alone. However, the small number of individuals treated concurrently limits the conclusions about the combination of both modalities, and the results from ongoing prospective clinical trials are eagerly awaited to understand both the toxicity profile and the clinical response fully.
Effect of Localized Vibration Massage on Popliteal Blood Flow
Authors: Needs Devin , Blotter Jonathan , Cowan Madison , Fellingham Gilbert , Johnson A. Wayne , Feland Jeffrey Brent
Published: March 2023

There is a broad scope of literature investigating whole-body vibration (WBV) effects on blood flow (BF). However, it is unclear how therapeutic localized vibrations alter BF. Low-frequency massage guns are advertised to enhance muscle recovery, which may be through BF changes; however, studies using these devices are lacking. Thus, the purpose of this study was to determine if popliteal artery BF increases from localized vibration to the calf. Twenty-six healthy, recreationally active university students (fourteen males, twelve females, mean age 22.3 years) participated. Each subject received eight therapeutic conditions randomized on different days with ultrasound blood flow measurements. The eight conditions combined either control, 30 Hz, 38 Hz, or 47 Hz for a duration of 5 or 10 min. BF measurements of mean blood velocity, arterial diameter, volume flow, and heart rate were measured. Using a cell means mixed model, we found that both control conditions resulted in decreased BF and that both 38 Hz and 47 Hz resulted in significant increases in volume flow and mean blood velocity, which remained elevated longer than the BF induced by 30 Hz. This study demonstrates localized vibrations at 38 Hz and 47 Hz significantly increase BF without affecting the heart rate and may support muscle recovery.
Use of Non-Contrast-Enhanced MR Angiography to Assess Recanalization after Uterine Artery Embolization
Authors: Ishisaki Juliana Yumi , Kato Hitomi , Kuwatsuru Yoshiki , Toei Hiroshi , Hoshina Ayako , Takemasa Naoki , Arai Masafumi , Kuwatsuru Ryohei
Published: March 2023

The purpose of this study was to examine the use of non-contrast-enhanced MR angiography (MRA) for assessing recanalization of uterine arteries (UAs) after uterine artery embolization (UAE) for symptomatic fibroids. Pre-procedural and follow-up unenhanced MRA images of 30 patients were reviewed, and the extent to which the UAs could be visualized was classified on a 4-point scale. An increase in the score between consecutive time points indicates that a previously inconspicuous segment of the UA became visible on follow-up images. Patients were divided into two groups according to the presence (or absence) of recanalization. The median UA visualization score at each follow-up was significantly lower than that at baseline (p < 0.01), but there was no significant difference between the scores of the follow-up images. Recanalization was detected in 63% (19/30) of patients. In these patients, the mean decrease in uterine and largest fibroid volume at 12 months after UAE was inferior to the mean decrease in patients for whom recanalization was not detected. Based on MRA assessment, recanalization after UAE occurred in 63% of patients but did not compromise the reduction in uterine and dominant fibroid volumes within 12 months after UAE.
Efficacy of Contrast-Enhanced Endoscopic Ultrasonography for the Differentiation of Non-Hodgkin’s Lymphoma: A Single-Center Retrospective Cohort Study
Authors: Yoshida Kensaku , Iwashita Takuji , Mita Naoki , Iwasa Yuhei , Uemura Shinya , Shimizu Masahito
Published: March 2023

Background: Contrast-enhanced endoscopic ultrasound (CE-EUS) is a promising diagnostic modality for differentiating malignant and benign lymph nodes. This study aimed to evaluate the diagnostic capability of CE-EUS in differentiating indolent non-Hodgkin’s lymphoma (NHL) from aggressive NHL. Methods: Patients who underwent CE-EUS and endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) for lymphadenopathy and were diagnosed with NHL were included in this study. Echo features on B-mode endoscopic ultrasound (EUS) and vascular and enhancement patterns on CE-EUS were qualitatively evaluated. The enhancement intensity of the lymphadenopathy on CE-EUS over 60 s was also quantitatively evaluated using time–intensity curve (TIC) analysis. Results: A total of 62 patients who were diagnosed with NHL were enrolled in this study. Regarding qualitative evaluation using B-mode EUS, there were no significant differences in the echo features between aggressive NHL and indolent NHL. With regard to qualitative evaluation using CE-EUS, aggressive NHL showed a heterogeneous enhancement pattern that is significantly more frequent than indolent NHL (95% confidence interval: 0.57 to 0.79, p = 0.0089). When heterogeneous enhancement was defined as aggressive NHL, the sensitivity, specificity, and accuracy of the qualitative evaluation when using CE-EUS were 61%, 72%, and 66%, respectively. In TIC analysis, the velocity of reduction for homogeneous lesions was significantly higher in aggressive NHL than in indolent NHL (p < 0.0001). The sensitivity, specificity, and accuracy of CE-EUS in differentiating indolent NHL from aggressive NHL improved to 94%, 69%, and 82%, respectively, when combined with qualitative and quantitative evaluations. Conclusions: CE-EUS before EUS-FNA for mediastinal or abdominal lymphadenopathy may be useful for improving the diagnostic capability of differentiating between indolent NHL and aggressive NHL (clinical trial registration number: UMIN000047907).
Evolution of the Diagnosis and Treatment of Primary Hyperparathyroidism
Authors: Battistella Enrico , Pomba Luca , Toniato Riccardo , Burei Marta , Gregianin Michele , Watutantrige Fernando Sara , Toniato Antonio
Published: March 2023

This study aims to present the evolution of our center’s approach to treating primary hyperparathyroidism (PHPT) from diagnosis to intraoperative interventions. We have also evaluated the intraoperative localization benefits of indocyanine green fluorescence angiography. This retrospective single-center study involved 296 patients who underwent parathyroidectomy for PHPT between January 2010 and December 2022. The preoperative diagnostic procedure included neck ultrasonography in all patients, [99mTc]Tc-MIBI scintigraphy in 278 patients, and, in 20 doubtful cases, [18F] fluorocholine positron emission tomography (PET) computed tomography (CT) was performed. Intraoperative PTH was measured in all cases. Indocyanine green has been administered intravenously since 2020 to guide surgical navigation using a fluorescence imaging system. The development of high precision diagnostic tools that can localize an abnormal parathyroid gland in combination with intra-operative PTH assay (ioPTH) enables the surgical treatment of PHPT patients with focused approaches and excellent results that are stackable with bilateral neck exploration (98% of surgical success). Indocyanine green angiography has the potential to assist surgeons in identifying parathyroid glands rapidly and with minimal risk, especially when pre-operative localization has failed. When everything else fails, it is only an experienced surgeon who can resolve the situation.
Radiomic Features from Post-Operative 18F-FDG PET/CT and CT Imaging Associated with Locally Recurrent Rectal Cancer: Preliminary Findings
Authors: Cuicchi Dajana , Mottola Margherita , Castellucci Paolo , Bevilacqua Alessandro , Cattabriga Arrigo , Cocozza Maria Adriana , Cardelli Stefano , Dajti Gerti , Mattoni Susanna , Golfieri Rita , Fanti Stefano , Cappelli Alberta , Coppola Francesca , Poggioli Gilberto
Published: March 2023

Locally Recurrent Rectal Cancer (LRRC) remains a major clinical concern; it rapidly invades pelvic organs and nerve roots, causing severe symptoms. Curative-intent salvage therapy offers the only potential for cure but it has a higher chance of success when LRRC is diagnosed at an early stage. Imaging diagnosis of LRRC is very challenging due to fibrosis and inflammatory pelvic tissue, which can mislead even the most expert reader. This study exploited a radiomic analysis to enrich, through quantitative features, the characterization of tissue properties, thus favoring an accurate detection of LRRC by Computed Tomography (CT) and 18F-FDG-Positron Emission Tomography/CT (PET/CT). Of 563 eligible patients undergoing radical resection (R0) of primary RC, 57 patients with suspected LRRC were included, 33 of which were histologically confirmed. After manually segmenting suspected LRRC in CT and PET/CT, 144 Radiomic Features (RFs) were generated, and RFs were investigated for univariate significant discriminations (Wilcoxon rank-sum test, p < 0.050) of LRRC from NO LRRC. Five RFs in PET/CT (p < 0.017) and two in CT (p < 0.022) enabled, individually, a clear distinction of the groups, and one RF was shared by PET/CT and CT. As well as confirming the potential role of radiomics to advance LRRC diagnosis, the aforementioned shared RF describes LRRC as tissues having high local inhomogeneity due to the evolving tissue’s properties.
Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients
Authors: Matsuda Yui , Tokumasu Kazuki , Otsuka Yuki , Sunada Naruhiko , Honda Hiroyuki , Sakurada Yasue , Nakano Yasuhiro , Hasegawa Toru , Obika Mikako , Ueda Keigo , Otsuka Fumio
Published: March 2023

Objectives: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients. Methods: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 μg/dL (10.7 μmol/L) were compared with characteristics of patients with normozincemia. Results: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = −0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 μg/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue. Conclusions: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients.
Biochemical Mechanisms beyond Glycosphingolipid Accumulation in Fabry Disease: Might They Provide Additional Therapeutic Treatments?
Authors: Bertoldi Giovanni , Caputo Ilaria , Driussi Giulia , Stefanelli Lucia Federica , Di Vico Valentina , Carraro Gianni , Nalesso Federico , Calò Lorenzo A.
Published: March 2023

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Currently, enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease’s progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. Several studies reported how secondary biochemical processes beyond Gb3 and lyso-Gb3 accumulation—such as oxidative stress, compromised energy metabolism, altered membrane lipid, disturbed cellular trafficking, and impaired autophagy—might exacerbate Fabry disease adverse outcomes. This review aims to summarize the current knowledge of these pathogenetic intracellular mechanisms in Fabry disease, which might suggest novel additional strategies for its treatment.
Safety Analysis of Bevacizumab in Ovarian Cancer Patients
Authors: Wang Yingwen , Lin Hao , Ou Yuche , Fu Hungchun , Tsai Chingchou , Chien Chanchao Chang , Wu Chenhsuan
Published: March 2023

Bevacizumab (BEV) is beneficial for ovarian cancer patients, but the real world’s patient settings differ from those in clinical trials. This study tries to illustrate adverse events in the Taiwanese population. Patients with epithelial ovarian cancer treated with BEV at Kaohsiung Chang Gung Memorial Hospital between 2009 and 2019 were retrospectively reviewed. The receiver operating characteristic curve was adopted to identify the cutoff dose and the presence of BEV-related toxicities. A total of 79 patients receiving BEV in neoadjuvant, frontline, or salvage settings were enrolled. The median follow-up time was 36.2 months. Twenty patients (25.3%) had “De novo” hypertension or the worsening of a preexisting one. Twelve patients (15.2%) had “De novo” proteinuria. Five patients (6.3%) had thromboembolic events/hemorrhage. Four patients (5.1%) had gastrointestinal perforation (GIP), and one patient (1.3%) had wound-healing complications. Patients with BEV-related GIP had at least two risk factors for developing GIP, most of which were conservatively managed. This study revealed a compatible but distinct safety profile from those reported in clinical trials. The presence of BEV-related changes in blood pressure showed a dose-dependent trend. Most of the BEV-related toxicities were managed individually. Patients with potential risks for developing BEV-related GIP should use BEV with caution.
Obesity Is Indirectly Associated with Sudden Cardiac Arrest through Various Risk Factors
Authors: Kim Yun Gi , Jeong Joo Hee , Roh Seung-Young , Han Kyung-Do , Choi Yun Young , Min Kyongjin , Shim Jaemin , Choi Jong-Il , Kim Young-Hoon
Published: March 2023

Although obesity is a well-established risk factor of cardiovascular event, the linkage between obesity and sudden cardiac arrest (SCA) is not fully understood. Based on a nationwide health insurance database, this study investigated the impact of body weight status, measured by body-mass index (BMI) and waist circumference, on the SCA risk. A total of 4,234,341 participants who underwent medical check-ups in 2009 were included, and the influence of risk factors (age, sex, social habits, and metabolic disorders) was analyzed. For 33,345,378 person-years follow-up, SCA occurred in 16,352 cases. The BMI resulted in a J-shaped association with SCA risk, in which the obese group (BMI ≥ 30) had a 20.8% increased risk of SCA compared with the normal body weight group (18.5 ≤ BMI < 23.0) (p < 0.001). Waist circumference showed a linear association with the risk of SCA, with a 2.69-fold increased risk of SCA in the highest waist circumference group compared with the lowest waist circumference group (p < 0.001). However, after adjustment of risk factors, neither BMI nor waist circumference was associated with the SCA risk. In conclusion, obesity is not independently associated with SCA risk based on the consideration of various confounders. Rather than confining the findings to obesity itself, comprehensive consideration of metabolic disorders as well as demographics and social habits might provide better understanding and prevention of SCA.
Multimodal Imaging Based Predictors for the Development of Choroidal Neovascularization in Patients with Central Serous Chorioretinopathy
Authors: Caplash Sonny , Surakiatchanukul Thamolwan , Arora Supriya , Maltsev Dmitrii S. , Singh Sumit Randhir , Sahoo Niroj Kumar , Parameshwarappa Deepika , Kulikov Alexei N. , Iovino Claudio , Tatti Filippo , Gujar Ramkailash , Venkatesh Ramesh , Reddy Nikitha Gurram , Snehith Ram , Peiretti Enrico , Lupidi Marco , Chhablani Jay
Published: March 2023

This study evaluated predictors for choroidal neovascularization (CNV) associated with central serous chorioretinopathy (CSCR) based on multimodal imaging. A retrospective multicenter chart review was conducted on 134 eyes of 132 consecutive patients with CSCR. Eyes were classified as per the multimodal imaging-based classification of CSCR at baseline into simple/complex CSCR and primary episode/recurrent/resolved CSCR. Baseline characteristics of CNV and predictors were evaluated with ANOVA. In 134 eyes with CSCR, 32.8% had CNV (n = 44) with 72.7% having complex CSCR (n = 32), 22.7% having simple (n = 10) and 4.5% having atypical (n = 2). Primary CSCR with CNV were older (58 vs. 47, p = 0.00003), with worse visual acuity (0.56 vs. 0.75, p = 0.01) and of longer duration (median 7 vs. 1, p = 0.0002) than those without CNV. Similarly, recurrent CSCR with CNV were older (61 vs. 52, p = 0.004) than those without CNV. Patients with complex CSCR were 2.72 times more likely to have CNV than patients with simple CSCR. In conclusion, CNV associated with CSCR was more likely in complex CSCR and older age of presentation. Both primary and recurrent CSCR are implicated in CNV development. Patients with complex CSCR were 2.72 times more likely to have CNV than patients with simple CSCR. Multimodal imaging-based classification of CSCR supports detailed analysis of associated CNV.
A Systematic Review of Lung Autopsy Findings in Elderly Patients after SARS-CoV-2 Infection
Authors: Septimiu-Radu Susa , Gadela Tejaswi , Gabriela Doros , Oancea Cristian , Rosca Ovidiu , Lazureanu Voichita Elena , Fericean Roxana Manuela , Bratosin Felix , Dumitrescu Andreea , Stoicescu Emil Robert , Bagiu Iulia , Murariu Mircea , Mavrea Adelina
Published: March 2023

Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals who died. Active autopsy results may be crucial for understanding how COVID-19 infection operates and preventing severe effects. In contrast to younger persons, however, the patient’s age, lifestyle, and concomitant comorbidities might alter the morpho-pathological aspects of the damaged lungs. Through a systematic analysis of the available literature until December 2022, we aimed to provide a thorough picture of the histopathological characteristics of the lungs in patients older than 70 years who died of COVID-19. A thorough search was conducted on three electronic databases (PubMed, Scopus, and Web of Science), including 18 studies and a total of 478 autopsies performed. It was observed that the average age of patients was 75.6 years, of which 65.4% were men. COPD was identified in an average of 16.7% of all patients. Autopsy findings indicated significantly heavier lungs, with an average weight of the right lung of 1103 g, while the left lung mass had an average weight of 848 g. Diffuse alveolar damage was a main finding in 67.2% of all autopsies, while pulmonary edema had a prevalence of between 50% and 70%. Thrombosis was also a significant finding, while some studies described focal and extensive pulmonary infarctions in 72.7% of elderly patients. Pneumonia and bronchopneumonia were observed, with a prevalence ranging from 47.6% to 89.5%. Other important findings described in less detail comprise hyaline membranes, the proliferation of pneumocytes and fibroblasts, extensive suppurative bronchopneumonic infiltrates, intra-alveolar edema, thickened alveolar septa, desquamation of pneumocytes, alveolar infiltrates, multinucleated giant cells, and intranuclear inclusion bodies. These findings should be corroborated with children’s and adults’ autopsies. Postmortem examination as a technique for studying the microscopic and macroscopic features of the lungs might lead to a better knowledge of COVID-19 pathogenesis, diagnosis, and treatment, hence enhancing elderly patient care.
Impact of Acrylic and Silicone-Based Soft-Liner Materials on Biting Force and Quality of Life of the Complete Denture Wearers: A Randomized Clinical Trial
Authors: Alqutaibi Ahmed Yaseen , Alnazzawi Ahmad A. , Farghal Ahmed E. , Bakr Ramy M. , Mahmoud Ihab Ismail
Published: March 2023

This rerandomized clinical trial evaluated the influence of soft liners (SL) on biting force, pain perception, and the oral health-related quality of life (OHRQoL) of complete denture wearers. Twenty-eight completely edentulous patients complaining of ill-fitting lower complete dentures were selected to participate in the study from the Dental Hospital, College of Dentistry, Taibah University. All patients received new complete maxillary and mandibular dentures; then they were randomly divided into two groups (14 patients in each group): the acrylic-based SL group, in which the mandibular denture was lined with an acrylic-based soft liner, and the silicone-based SL group, in which the mandibular denture was lined with a silicone-based soft liner. OHRQoL and maximum bite force (MBF) were assessed in this study before denture relining (baseline), then at one month and three months after relining. The finding showed that both treatment modalities significantly improved the OHRQoL of included patients at one-month and three-month periods compared to baseline records (i.e., dentures before relining) with a statistically significant difference (p < 0.05). However, there is no statistical difference between groups at the baseline, one-, and three-month follow-up periods. Regarding maximum biting force, when acrylic-based SL is compared to silicone-based SL, there is no statistical difference between groups at baseline (75 ± 31 and 83 ± 32 N) and one-month follow-up periods (145 ± 53 and 156 ± 49 N); however, after three months of function, the silicone-based group recorded 166 ± 57 N statistically significant high biting force compared to the acrylic-based group that recorded 116 ± 47 N (p < 0.05). Permanent soft denture liners positively affect maximum biting force, pain perception, and OHRQoL more than conventional dentures. After three months, silicone-based SL outperformed acrylic-based soft liners in maximum biting force, which may indicate better long-term results.
Performance Evaluation of an Improved ANFIS Approach Using Different Algorithms to Predict the Bonding Strength of Glulam Adhered by Modified Soy Protein–MUF Resin Adhesive
Authors: Nazerian Morteza , Naderi Fatemeh , Papadopoulos Antonios N.
Published: March 2023

Despite studies on the potential replacement of synthetic resins by bio-based adhesives such as proteins in recent years, there is still no reliable method for estimating the strength of wood products made using the combined parameters in the literature. This limitation is due to the nonlinear relationship between strength and the combined components. In the present research, the application of artificial intelligence techniques was studied to predict the bonding strength of glulam adhered by protein containing different ratios of MUF (melamine–urea–formaldehyde) resin with different F-to-U/M molar ratios at different press temperatures. For this purpose, the ANFIS artificial intelligence model was used as basic mode or combined with ant colony optimization (ACOR), particle swarm optimization (PSO), differential evaluation (DE) and genetic algorithms (GA) to develop an optimal trained model to predict the bonding strength of glulam based on experimental results. Comparison of the obtained results with the experimental results showed the ability of the above methods to estimate the bonding strength of glulam in a reliable manner. Although the basic ANFIS alone and in combination with other algorithms was not able to achieve an ideal performance prediction to estimate bonding strength, the combination of GA and ANFIS offered an excellent ability compared to the combination of other algorithms combined with ANFIS. Hence, the developed ANFIS-GA model is introduced as the best prediction technique to solve bonding strength problems of laminated products. In addition, using the developed optimal model, a precise attempt was made to show the nature of the parameters used to produce glulam and determine the optimum limit.
Biodegradable Cements for Bone Regeneration
Authors: Liu Dachuan , Cui Chen , Chen Weicheng , Shi Jiaxu , Li Bin , Chen Song
Published: March 2023

Bone cements such as polymethyl methacrylate and calcium phosphates have been widely used for the reconstruction of bone. Despite their remarkable clinical success, the low degradation rate of these materials hampers a broader clinical use. Matching the degradation rate of the materials with neo bone formation remains a challenge for bone-repairing materials. Moreover, questions such as the mechanism of degradation and how the composition of the materials contribute to the degradation property remain unanswered. Therefore, the review provides an overview of currently used biodegradable bone cements such as calcium phosphates (CaP), calcium sulfates and organic-inorganic composites. The possible degradation mechanism and clinical performance of the biodegradable cements are summarized. This paper reviews up-to-date research and applications of biodegradable cements, hoping to provide researchers in the field with inspirations and references.
Physicochemical, Morphological, and Cytotoxic Properties of Brazilian Jackfruit (Artocarpus heterophyllus) Starch Scaffold Loaded with Silver Nanoparticles
Authors: Rodrigues José Filipe Bacalhau , Azevedo Valeriano Soares , Medeiros Rebeca Peixoto , Barreto Gislaine Bezerra de Carvalho , Pinto Maria Roberta de Oliveira , Fook Marcus Vinicius Lia , Montazerian Maziar
Published: March 2023

Due to the physical, thermal, and biological properties of silver nanoparticles (AgNPs), as well as the biocompatibility and environmental safety of the naturally occurring polymeric component, polysaccharide-based composites containing AgNPs are a promising choice for the development of biomaterials. Starch is a low-cost, non-toxic, biocompatible, and tissue-healing natural polymer. The application of starch in various forms and its combination with metallic nanoparticles have contributed to the advancement of biomaterials. Few investigations into jackfruit starch with silver nanoparticle biocomposites exist. This research intends to explore the physicochemical, morphological, and cytotoxic properties of a Brazilian jackfruit starch-based scaffold loaded with AgNPs. The AgNPs were synthesized by chemical reduction and the scaffold was produced by gelatinization. X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS), and Fourier-transform infrared spectroscopy (FTIR) were used to study the scaffold. The findings supported the development of stable, monodispersed, and triangular AgNPs. XRD and EDS analyses demonstrated the incorporation of silver nanoparticles. AgNPs could alter the scaffold’s crystallinity, roughness, and thermal stability without affecting its chemistry or physics. Triangular anisotropic AgNPs exhibited no toxicity against L929 cells at concentrations ranging from 6.25 × 10−5 to 1 × 10−3 mol·L−1, implying that the scaffolds might have had no adverse effects on the cells. The scaffolds prepared with jackfruit starch showed greater crystallinity and thermal stability, and absence of toxicity after the incorporation of triangular AgNPs. These findings indicate that jackfruit is a promising starch source for developing biomaterials.
Characterization of Cyclic Olefin Copolymers for Insulin Reservoir in an Artificial Pancreas
Authors: Mallegni Norma , Milazzo Mario , Cristallini Caterina , Barbani Niccoletta , Fredi Giulia , Dorigato Andrea , Cinelli Patrizia , Danti Serena
Published: March 2023

Type-1 diabetes is one of the most prevalent metabolic disorders worldwide. It results in a significant lack of insulin production by the pancreas and the ensuing hyperglycemia, which needs to be regulated through a tailored administration of insulin throughout the day. Recent studies have shown great advancements in developing an implantable artificial pancreas. However, some improvements are still required, including the optimal biomaterials and technologies to produce the implantable insulin reservoir. Here, we discuss the employment of two types of cyclic olefin copolymers (Topas 5013L-10 and Topas 8007S-04) for an insulin reservoir fabrication. After a preliminary thermomechanical analysis, Topas 8007S-04 was selected as the best material to fabricate a 3D-printed insulin reservoir due to its higher strength and lower glass transition temperature (Tg). Fiber deposition modeling was used to manufacture a reservoir-like structure, which was employed to assess the ability of the material to prevent insulin aggregation. Although the surface texture presents a localized roughness, the ultraviolet analysis did not detect any significant insulin aggregation over a timeframe of 14 days. These interesting results make Topas 8007S-04 cyclic olefin copolymer a potential candidate biomaterial for fabricating structural components in an implantable artificial pancreas.
Ceramic Materials for Biomedical Applications: An Overview on Properties and Fabrication Processes
Authors: Vaiani Lorenzo , Boccaccio Antonio , Uva Antonio Emmanuele , Palumbo Gianfranco , Piccininni Antonio , Guglielmi Pasquale , Cantore Stefania , Santacroce Luigi , Charitos Ioannis Alexandros , Ballini Andrea
Published: March 2023

A growing interest in creating advanced biomaterials with specific physical and chemical properties is currently being observed. These high-standard materials must be capable to integrate into biological environments such as the oral cavity or other anatomical regions in the human body. Given these requirements, ceramic biomaterials offer a feasible solution in terms of mechanical strength, biological functionality, and biocompatibility. In this review, the fundamental physical, chemical, and mechanical properties of the main ceramic biomaterials and ceramic nanocomposites are drawn, along with some primary related applications in biomedical fields, such as orthopedics, dentistry, and regenerative medicine. Furthermore, an in-depth focus on bone-tissue engineering and biomimetic ceramic scaffold design and fabrication is presented.
Degassing a Decellularized Scaffold Enhances Wound Healing and Reduces Fibrosis during Tracheal Defect Reconstruction: A Preliminary Animal Study
Authors: Viet-Nhi Nguyen-Kieu , Chen Yen-Chun , Dang Luong Huu , Tseng How , Hung Shih-Han
Published: March 2023

Few efforts have been made regarding the optimization of porcine small intestinal submucosa (SIS) to improve its biocompatibility. This study aims to evaluate the effect of SIS degassing on the promotion of cell attachment and wound healing. The degassed SIS was evaluated in vitro and in vivo, compared with the nondegassed SIS control. In the cell sheet reattachment model, the reattached cell sheet coverage was significantly higher in the degassed SIS group than in the nondegassed group. Cell sheet viability was also significantly higher in the SIS group than in the control group. In vivo studies showed that the tracheal defect repaired by the degassed SIS patch showed enhanced healing and reductions in fibrosis and luminal stenosis compared to the nondegassed SIS control group, with the thickness of the transplanted grafts in the degassed SIS group significantly lower than those in the control group (346.82 ± 28.02 µm vs. 771.29 ± 20.41 µm, p < 0.05). Degassing the SIS mesh significantly promoted cell sheet attachment and wound healing by reducing luminal fibrosis and stenosis compared to the nondegassed control SIS. The results suggest that the degassing processing might be a simple and effective way to improve the biocompatibility of SIS.
It Runs in the Family: Testing for Longitudinal Family Flynn Effects
Authors: Wänström Linda , O’Keefe Patrick , Clouston Sean A. P. , Mann Frank D. , Muniz-Terrera Graciela , Voll Stacey , Zhang Yun , Hofer Scott M. , Rodgers Joseph L.
Published: March 2023

The Flynn effect refers to increases over time in measured (particularly fluid) intelligence of approximately 3 IQ points per decade. We define the Flynn effect at the family level, using longitudinal data and two new family-level cohort definitions. Multilevel growth curve analyses of the National Longitudinal Survey of Youth 1979 data showed that children in families with later-born mothers had higher average PIAT math scores, and lower average reading comprehension scores and growth, in young and middle childhood. Children in families where the first child was born later had higher average PIAT math, reading recognition, and reading comprehension scores, as well as larger developmental growth. The latter family-level Flynn effects were of higher magnitudes than the usual individual-level Flynn effect found in previous studies. Our results, showing family level-intercept and slope Flynn effects for both maternal birthyear and first child birthyear, have implications for research aiming to explain the Flynn effect.