bluuebunny/crossref_metadata_2025 huggingface dataset:
A Scoring Model with Simple Clinical Parameters to Predict Successful Discontinuation of Continuous Renal Replacement Therapy
Authors: Baeg Song In , Jeon Junseok , Yoo Heejin , Na Soo Jin , Kim Kyunga , Chung Chi Ryang , Yang Jeong Hoon , Jeon Kyeongman , Lee Jung Eun , Huh Wooseong , Suh Gee Young , Kim Yoon-Goo , Kim Dae Joong , Jang Hye Ryoun
Published: March 2021

Background: Continuous renal replacement therapy (CRRT) is the standard treatment for severe acute kidney injury in critically ill patients. However, a practical consensus for discontinuing CRRT is lacking. We aimed to develop a prediction model with simple clinical parameters for successful discontinuation of CRRT. Methods: Adult patients who received CRRT at Samsung Medical Center from 2007 to 2017 were included. Patients with preexisting ESRD and patients who progressed to ESRD within 1 year or died within 7 days after CRRT were excluded. Successful discontinuation of CRRT was defined as no requirement for renal replacement therapy for 7 days after discontinuing CRRT. Patients were assigned to either a success group or failure group according to whether discontinuation of CRRT was successful or not. Results: A total of 1,158 patients were included in the final analyses. The success group showed greater urine output on the day before CRRT discontinuation (D-1) and the discontinuation day (D0). Multivariable analysis identified that urine output ≥300 mL on D-1, and mean arterial pressure 50∼78 mm Hg, serum potassium <4.1 mmol/L, and BUN <35 mg/dL (12.5 mmol/L) on D0 were predictive factors for successful discontinuation of CRRT. A scoring system using the 4 variables above (area under the receiver operating curve: 0.731) was developed. Conclusions: Scoring system composed of urine output ≥300 mL/day on D-1, and adequate blood pressure, serum potassium <4.1 mmol/L, and BUN <35 mg/dL (12.5 mmol/L) on D0 was developed to predict successful discontinuation of CRRT.
Prognostic Factors in Penile Cancer: Should We Avoid Inguinal Lymph Node Staging?
Authors: Vale Luís , Fernandes Bernardo , Rodrigues Vasco , Dinis Paulo , Silva Carlos , Antunes-Lopes Tiago
Published: March 2021

Introduction: Penile cancer (PC) is a rare neoplasm, mostly in developed countries. Herewith, we evaluate the main prognostic factors of patients with PC undergoing surgery. Methods: This is a retrospective analysis of prognostic factors of overall survival in 65 patients with PC treated at a tertiary referral center over the last 15 years (2004–2018). Results: Almost half (48%) of the patients were diagnosed at an advanced local stage pT3/4. Thirty-eight (58%) patients underwent inguinal lymphadenectomy, and 25 (66%) were negative for lymph node (LN) invasion. Overall survival was 80% at a median follow-up of 31 months. In the multivariate analysis, the main factors of poor prognosis were nodal staging (pN) (p = 0.008) and perineural invasion (p = 0.023). The presence of LN metastasis and perineural invasion in the primary tumor increased the risk of death by 29 (hazard ratio 29.0, 95% confidence interval 2.4–354.2) and 13 (hazard ratio 12.7, 95% confidence interval 1.4–112.0) times, respectively. Discussion/Conclusion: Late diagnosis of PC has a negative impact on overall survival, as nodal invasion correlates with survival. Despite the high number of negative inguinal lymphadenectomy, we continue to advocate aggressive surgical treatment of this disease due to the poor prognosis associated with LN metastasis.
Efficacy and Safety of Sacubitril/Valsartan Therapy for Acute Decompensated Heart Failure with Reduced Ejection Fraction during the Vulnerable Phase: A Multicenter, Assessor-Blinded, Prospective, Observational, Cohort Study
Authors: He Yun , Lu Xuemei , Zheng Yi , Song Mingbao , Shen Bin , Nienaber Christoph A. , Chen Guozhu , Wu Feng , Zheng Jing , Zhang Weihong , Wang Yaping , Li Xiaorong , Wen Hongcan , Yu Xiaoqian , Zhou Yinpin
Published: March 2021

Background: The 3-month period after hospitalization for acute cardiac failure is a vulnerable phase with the highest risk of mortality and rehospitalization. Safety and efficacy of early initiation of sacubitril/valsartan during the index hospitalization for acute decompensated heart failure (ADHF) is unclear. Therefore, we tested whether sacubitril/valsartan could result in a lower rate of a composite outcome of first hospitalization for heart failure and death from cardiovascular causes compared to inhibition of the renin-angiotensin system alone. Methods: We enrolled patients hospitalized for ADHF and reduced ejection fraction at 4 sites; patients were divided into a sacubitril/valsartan group or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) group. All patients were followed up for 3 months after discharge. The primary endpoint was outcomes as a composite of death from cardiovascular causes and rehospitalization for heart failure. Results: In total, 251 patients who received sacubitril/valsartan and 251 patients who received ACEIs/ARBs had similar propensity scores and were included and compared. The primary endpoint was reached in 40 patients (15.9%) treated with sacubitril/valsartan and in 59 patients (23.5%) managed by ACEI/ARB (HR, 0.650; 95% CI: 0.435–0.971; p = 0.035). The NYHA class improved in 72.1% of patients in the sacubitril/valsartan group and in 59.8% of patients in the ACEI/ARB group (HR, 1.303; 95% CI: 1.097–1.548, p = 0.004). The key safety outcomes endpoints did not significantly differ. Conclusions: Among patients hospitalized with ADHF and reduced left ventricular ejection fraction, we observed that sacubitril/valsartan therapy led to reduction in death from cardiovascular causes and rehospitalizations for heart failure when compared to ACEI/ARB therapy alone during the vulnerable phase. Our results support that sacubitril/valsartan may be administered early in the vulnerable phase after ADHF and improves NYHA class.
National Cardiovascular Data Registry Model Predicts Long-Term Mortality in Patients Undergoing Percutaneous Coronary Interventions
Authors: Agasthi Pradyumna , Chao Chieh-Ju , Wang Panwen , Yang Eric H. , Arsanjani Reza
Published: March 2021

National Cardiovascular Data Registry (NCDR)-based logistic regression model is available for clinicians to predict in-hospital all-cause mortality after a percutaneous coronary intervention (PCI). However, this model has never been used to predict long-term all-cause mortality after PCI. Therefore, we sought to test the ability of the NCDR model to predict the short- and long-term risk of all-cause mortality in patients undergoing PCI. All patients undergoing PCI in the Mayo Clinic Health System were enrolled in the Mayo Clinic CathPCI registry. Patient-level demographic, clinical, and angiographic data from January 2006 to December 2017 were extracted from the registry. Patients who underwent coronary artery bypass graft surgery (CABG) were excluded. The area under the receiver operator characteristic curve (AUC) was calculated to assess the ability of the NCDR model to predict outcomes of interest (6-month, 1-year, 2-year, and 5-year all-cause mortality) after PCI. A total of 17,356 unique patients were included for the final analysis after excluding 165 patients who underwent CABG surgery. The mean age was 66.9 ± 12.5 years, and 71% were men. The 6-month, 1-year, 2-year, and 5-year all-cause mortality rates were 4.2% (n = 737), 5.8% (n = 1,005), 8.06% (n = 1,399), and 14.2% (n = 2,472), respectively. The AUCs of the NCDR model to predict 6-month, 1-year, 2-year, and 5-year all-cause mortality were 0.84 (95% CI: 0.82–0.86), 0.82 (95% CI: 0.80–0.84), 0.80 (95% CI: 0.79–0.81), and 0.78 (95% CI: 0.77–0.79), respectively. The NCDR model was able to accurately predict both short- and long-term all-cause mortality after PCI.
The Added Value of Inflow-Based Vascular-Space-Occupancy and Diffusion-Weighted Imaging in Preoperative Grading of Gliomas
Authors: Cao Haimei , Xiao Xiang , Hua Jun , Huang Guanglong , He Wenle , Qin Jie , Wu Yuankui , Li Xiaodan
Published: March 2021

Objectives: The present study aimed to study whether combined inflow-based vascular-space-occupancy (iVASO) MR imaging (MRI) and diffusion-weighted imaging (DWI) improve the diagnostic accuracy in the preoperative grading of gliomas. Methods: Fifty-one patients with histopathologically confirmed diffuse gliomas underwent preoperative structural MRI, iVASO, and DWI. We performed 2 qualitative consensus reviews: (1) structural MR images alone and (2) structural MR images with iVASO and DWI. Relative arteriolar cerebral blood volume (rCBVa) and minimum apparent diffusion coefficient (mADC) were compared between low-grade and high-grade gliomas. Receiver operating characteristic (ROC) curve analysis was performed to compare the tumor grading efficiency of rCBVa, mADC, and the combination of the two parameters. Results: Two observers diagnosed accurate tumor grade in 40 of 51 (78.4%) patients in the first review and in 46 of 51 (90.2%) in the second review. Both rCBVa and mADC showed significant differences between low-grade and high-grade gliomas. ROC analysis gave a threshold value of 1.52 for rCBVa and 0.85 × 10−3 mm2/s for mADC to provide a sensitivity and specificity of 88.0 and 81.2% and 100.0 and 68.7%, respectively. The area under the ROC curve (AUC) was 0.87 and 0.85 for rCBVa and mADC, respectively. The combination of rCBVa and mADC values increased the AUC to 0.92. Conclusion: The combined application of iVASO and DWI may improve the diagnostic accuracy of glioma grading.
Analysis of Copy Number Variations by Low-Depth Whole-Genome Sequencing in Fetuses with Congenital Cardiovascular Malformations
Authors: Huang Jiwei , Deng Xine , Wang Yuanliu , Tang Ning , Zeng Dingyuan
Published: March 2021

Congenital cardiovascular malformations (CVMs) due to genomic mutations bring a greater risk of morbidity and comorbidity and increase the risks related to heart surgery. However, reports on CVMs induced by genomic mutations based on actual clinical data are still limited. In this study, 181 fetuses were screened by fetal echocardiography for prenatal diagnosis of congenital heart disease, including 146 cases without ultrasound extracardiac findings (Group A) and 35 cases with ultrasound extracardiac findings (Group B). All cases were analyzed by clinical data, karyotyping, and low-depth whole-genome sequencing. The rates of chromosomal abnormalities in Groups A and B were 4.8% (7/146) and 37.1% (13/35), respectively. There was a significant difference in the incidence of chromosomal abnormalities between Groups A and B (p < 0.001). In Group A, CNV-seq identified copy number variations (CNVs) in an additional 9.6% (14/146) of cases with normal karyotypes, including 7 pathogenic CNVs and 7 variations of uncertain clinical significance. In Group B, one pathogenic CNV was identified in a case with normal karyotype. Chromosomal abnormality is one of the most common causes of CVM with extracardiac defects. Low-depth whole-genome sequencing could effectively become a first approach for CNV diagnosis in fetuses with CVMs.
Relationship between Endolymphatic Hydrops and Symptoms of Meniere Disease in Acoustic Hearing
Authors: Oh Yoonkyung , Lim Jongwoo , Cho Young Sang , Kim Namkeun
Published: March 2021

Hypothesis: The endolymphatic hydrops (EH) does not affect hearing loss significantly at low frequencies, whereas the hydrops affects the diplacusis. Background: There have been many arguments whether the EH cause the Meniere disease. Despite a lot of experimental studies to investigate the Meniere disease, there have been little modeling studies, which are helpful to understand the mechanism. Methods: A 3D finite element model of the human cochlea and the middle ear was used for investigation of the relationship between EH and hearing loss at low frequencies and diplacusis (2 specific symptoms of Meniere disease). While the cochlear geometry was simplified as a tapered box shape, the middle ear was based on the real geometry obtained from μCT images. EH is implemented by prestress on the basilar membrane surface in the simulation. Results: The EH did not cause significant hearing loss at low frequencies in both air- and bone-conducted hearing. Rather, this disorder caused a shift in best frequency (BF) position to the base at low frequencies below about 250 Hz. The BF shift can explain the diplacusis because a low-frequency sound can be perceived as a slightly higher frequency so that Meniere patients can perceive 2 different frequency sounds corresponding to a given single-frequency sound. Conclusion: The EH cannot be a sufficient condition for Meniere disease, whereas the hydrops can cause the diplacusis.
Fat-Free Mass Index Controlled for Age and Sex and Malnutrition Are Predictors of Survival in Interstitial Lung Disease
Authors: Rinaldi Sylvia , Gilliland Jason , O’Connor Colleen , Seabrook Jamie A. , Mura Marco , Madill Janet
Published: March 2021

Background: Literature focusing on nutritional variables and survival in interstitial lung disease (ILD) is limited by its focus on weight and BMI and has not considered body composition. Objectives: The primary objective of this study was to examine whether body composition measures, specifically fat-free mass index z-score (z-FFMI) and body fat mass index z-score (z-BFMI), were predictors of survival in fibrotic ILD patients. The second objective was to examine if nutrition status was a predictor of survival. Method: Seventy-eight outpatients diagnosed with fibrotic ILD were recruited in this cross-sectional study. Body composition data using dual frequency bioelectrical impedance analysis (BodyStat 1500MD; UK) and nutrition status using the subjective global assessment (SGA) were determined. To control for age and sex, z-FFMI and z-BFMI were calculated using population means. Participant charts were reviewed for diagnosis, age, disease severity, and exercise capacity. Results: Age (HR 1.08, 95% CI [1.03–1.13], p < 0.01), BMI (HR 0.90, 95% CI [0.84–0.97], p < 0.01]), z-FFMI (HR 0.70, 95% CI [0.56–0.87], p = 0.02), z-BFMI (HR 0.74, 95% CI [0.57–0.96], p < 0.01), 6-min walk distance (6MWD) (HR 0.99, 95% CI [0.99–1.00], p < 0.01), percent predicted diffusing capacity for carbon monoxide (%DLco) (HR 0.93, 95% CI [0.89–0.97], p < 0.01), and severe malnutrition (SGA-C) (HR 6.98, 95% CI [2.00–24.27], p < 0.01) were significant predictors of survival. When controlled for exercise capacity and disease severity, z-FFMI and severe malnutrition were significant predictors of survival independent of %DLco. Conclusion: z-FFMI and severe malnutrition were significant predictors of survival in fibrotic ILD patients independent of disease severity.
Impact of Perioperative Tachydysrhythmias on Mortality and Length of Stay in Complete Repair of Tetralogy of Fallot: A Multicenter Retrospective Cohort Study from the Pediatric Health Information System
Authors: Ahmed Aziez , Prodhan Parthak , Spray Beverly J. , Bolin Elijah H.
Published: March 2021

Introduction: Tachydysrhythmias (TDS) frequently occur after complete repair of tetralogy of Fallot (TOF). However, not much is known about the effect of TDS on morbidity and mortality after TOF repair. We sought to assess the associations between TDS and mortality and morbidity after repair of TOF using a multicentre database. Materials and Methods: We identified all children aged 0–5 years in the Pediatric Health Information System who underwent TOF repair between 2004 and 2015. Codes for TDS were used to identify cases. Outcome variables were inpatient mortality and total length of stay (LOS). Univariate and multiple logistic and linear regression analyses were used to identify the effects of multiple risk factors, including TDS, on mortality and LOS. Results: A total of 7,749 patients met inclusion criteria, of which 1,493 (19%) had codes for TDS. There was no association between TDS and inpatient mortality. However, TDS were associated with 1.1 days longer LOS and accounted for 2% of the variation observed in LOS. Conclusion: After complete repair of TOF, TDS were not associated with mortality and appeared to have only a modest effect on LOS.
Health Outcomes and Cost Considerations of Assisted Peritoneal Dialysis: A Narrative Review
Authors: Maierean Serban M. , Oliver Matthew J.
Published: March 2021

Background: Peritoneal dialysis (PD) is underutilized in many parts of the world despite pro-PD health policies. The physical and cognitive demands of PD means that over half of eligible patients require some form of assistance. As such, many countries now offer assisted PD (aPD) programs to help patients start or stay on PD as opposed to in-center hemodialysis (HD). In order to evaluate the potential scope of aPD, it is important to review the outcomes and cost considerations of aPD. Summary: We reviewed available data from different countries and regions for health outcomes between aPD and in-center HD, with a focus on quality of life (QoL), mortality, hospitalization, and technique survival. We also evaluated studies discussing the overall costs of delivering aPD, including training, operating costs, and indirect costs and compared these to in-center HD costs for the same regions. Key Messages: aPD patients are older and more frail than either self-care PD patients and many in-center HD patients. We found no evidence for any difference in QoL, mortality, or hospitalization between aPD and in-center HD after adjustment for these differences. There is some evidence for an association between nurse assistance and improved technique survival as compared to family assistance or self-care PD. Despite increased cost of providing assistance in PD, it is still significantly less expensive than in-center HD in Western Europe and Canada.
Penetrating Craniocerebral Injury by the Hook of a School Desk
Authors: Guvenc Yahya , Sakar Mustafa , Niftaliyev Seymur , Guliyev Abdulmammad , Simsek Ismail , Dağçınar Adnan
Published: March 2021

Introduction: Although penetrating cranial injuries are rare in pediatric patients, these injuries can lead to morbidity and mortality. Removal of a gigantic foreign body from the cranium requires proper management as it has high risk of further brain damage and seizures. Case Presentation: We report the case of a patient with cranial injury caused by hitting the head to the hook of a school desk. Due to the extreme nature of the injury, the following additional steps were necessary: taking help from a local firefighter team to cut the desk, surgical removal of the foreign body, and cranioplasty after 6 months. Following this, he was discharged without neurological deficits. Discussion/Conclusion: Neurotrauma is one of the major causes of death in children. The damage and effect of the injuring foreign body depends on its size, shape, velocity, trajectory, and entry point. It should be kept in mind that any high-frequency processes applied on the extracranial parts of conductive objects, such as metal bars, may trigger seizures. Preoperative extracranial intervention for huge penetrating foreign bodies should be performed under anticonvulsant administration and intubation to decrease the risk of epileptic seizures and its complications.
Six1 Promotes Epithelial-Mesenchymal Transition in Bronchial Epithelial Cells via the TGFβ1/Smad Signalling Pathway
Authors: Wang Wenxin , Yang Zhaochuan , Li Meixiang , Wang Zhenhong , Shan Yanchun , Qu Zhenghai
Published: March 2021

Introduction: The homeodomain transcription factor sine oculis homeobox homolog 1 (Six1) plays a crucial role in embryogenesis and is not expressed in normal adult tissue but is expressed in many pathological processes, including airway remodelling in asthma. The current study aimed to reveal the effects of Six1 in regulating the airway remodelling and its possible mechanism. Methods: A mouse model of ovalbumin-induced asthma-associated airway wall remodelling and a bronchial epithelial cell (16HBE) model of transforming growth factor β1 (TGFβ1)-induced epithelial-mesenchymal transition (EMT) were used to investigate the role of Six1. Then, 16HBE cells were transformed with Six1 expression vectors and treated with a TGFβ1 pathway inhibitor to determine the role of Six1 in EMT. The effect of Six1 and its possible mechanism were assessed by immunohistochemistry, RT-PCR, and Western blot. Results: Six1 expression was elevated in the lungs in an OVA mouse model of allergic asthma and in 16HBE cells treated with TGFβ1. Six1 overexpression promoted an EMT-like phenotype with a decreased protein expression of E-cadherin and increased protein expression of α-smooth muscle actin (α-SMA) as well as fibronectin in 16HBE cells; these effects appeared to promote TGFβ1 and phospho-Smad2 (pSmad2) production, which are the main products of the TGFβ1/Smad signalling pathway, which could be reduced by a TGFβ1 inhibitor. Conclusion: These data reveal that Six1 and TGFβ1 are potentially a part of an autocrine feedback loop that induces EMT, and these factors can be reduced by blocking the TGFβ1/Smad signalling pathway. As such, these factors may represent a promising novel therapeutic target for airway remodelling in asthma.
Potential of Perfusion Magnetic Resonance Imaging to Predict Residual Renal Function after Radical Nephroureterectomy
Authors: Waseda Yuma , Yoshida Soichiro , Arita Yuki , Takahara Taro , Sakamoto Tsuyoshi , Saito Kazutaka , Fujii Yasuhisae
Published: March 2021

Introduction: The diffusion-weighted imaging (DWI) technique with intravoxel incoherent motion model enables the estimation of capillary blood volume as a perfusion-related parameter- (PP-) value. Therefore, the PP-value of the kidney theoretically reflects renal capillary blood volume. We analyzed the usefulness of the PP-value in estimating postoperative renal function in upper-tract urothelial carcinoma (UTUC) patients. Methods: Forty-eight consecutive patients who underwent magnetic resonance imaging before radical nephroureterectomy from 2011 to 2018 were analyzed. A PP-map displaying PP-values on a pixel-by-pixel basis was created from DWI signals (b-values of 0, 500, and 1,000 s/mm2). Two readers independently analyzed the renal PP-value. DWI-based split renal function (SRF) of the intact kidney was calculated by splitting serum Cr-based preoperative estimated glomerular filtration rates (eGFRs). The predictive accuracy of the method was evaluated using renography as the reference standard. Results: Interobserver analysis revealed an excellent correlation value of 0.97. The SRF value showed a good linear correlation with the observed postoperative eGFR (r = 0.76, p < 0.001). The predictive accuracy of the DWI-based method was similar to that of the nuclear-based method. Conclusion: This DWI-based evaluation of capillary blood volume provides a noninvasive tool for predicting the postoperative renal function, thereby facilitating the management of UTUC patients.
Risk Factors for a Complicated Postoperative Course in Flexible Ureteroscopy
Authors: Ozimek Tomasz , Hochguertel Laura , Hupe Marie C. , Struck Julian P. , Wiessmeyer Judith R. , Gilbert Nils , Merseburger Axel S. , Kramer Mario W.
Published: March 2021

Introduction: The goal was to determine risk factors for Clavien-Dindo (CD) grade ≥2 complications, with special focus on early postoperative systemic inflammatory response syndrome (SIRS), for flexible ureteroscopy (fURS). Materials and Methods: A retrospective monocentric statistical analysis relating to 32 factors was performed with the χ2 test, Mann-Whitney U tests, and multivariate logistic regression. Results: In total, 416 consecutive fURS performed between September 2013 and June 2017 were analyzed; 283 (68.03%) of these were for stone surgery and 133 (31.97%) for diagnostic purposes. In 43 cases (10.34%), CD ≥2 occurred; 31 cases (72.09%) of these were SIRS. On multivariate logistic regression, positive preoperative urine culture and steep pyelographic and CT-based infundibulopelvic angle (IPA) have been confirmed as independent risk factors for both CD ≥2 and SIRS. Greater maximal median stone diameter and female gender were significantly associated only with a higher CD ≥2 prevalence, but not with SIRS. The influence of ureteral access sheath (UAS) on CD ≥ 2 or SIRS occurrence could not be confirmed on multivariate analysis. Perioperative antibiotic prophylaxis for patients with negative urine culture showed no difference regarding SIRS prevalence. Conclusion: Steep CT-based IPA can be considered as a new radiologic predictor of complicated postoperative course and SIRS. The role of UAS as well as indications for perioperative antibiotic prophylaxis should be determined in prospective studies.
Analysis of Key Distinct Biological Characteristics of Human Placenta-Derived Mesenchymal Stromal Cells and Individual Heterogeneity Attributing to Donors
Authors: Tai Chenxu , Wang Liudi , Xie Yuanyuan , Gao Tianyun , Huang Feifei , Wang Bin
Published: March 2021

For potential clinical applications in the future, we investigated the distinct biological features of mesenchymal stromal cells (MSCs) derived from different origin areas of human placenta and individual heterogeneity among different donors. Chorionic plate MSCs (CP-MSCs), amniotic membrane MSCs (AM-MSCs), and decidual plate MSCs (DP-MSCs) were isolated from 5 human placentae and were analyzed in terms of main features of MSCs including surface marker profile, growth, differentiation potential, immune regulation capability, and tubulin acetylation (Ac-tubulin). The expression profile of surface markers in the 3 types of MSCs derived from the 5 donors was relatively stable. Heterogeneity was found in growth, differentiation potential, and immune regulation among MSCs according to the different areas of isolation and different donors. CP-MSCs and AM-MSCs derived from the placentae of donors 1–3 had a higher osteogenic differentiation potential than the corresponding DP-MSCs, but those derived from the placentae of donors 4 and 5 had a markedly lower osteogenic differentiation potential than DP-MSCs. All CP-MSCs derived from donors 1–3 had the highest adipogenic differentiation potential, but CP-MSCs derived from donors 4 and 5 did not show strong capability of adipogenic differentiation. CP-MSCs markedly inhibited the proliferation of peripheral blood mononuclear cells (PBMCs) induced by phytohemagglutinin, whereas AM- and DP-MSCs did not. All MSCs decreased the proportion of CD3+/CD8–/IFN-γ+ Th1 and CD3+/CD8–/IL17+ Th17 cells, but increased the proportion of Treg cells in PBMCs, with individual differences among the 5 donors. DP-MSCs from donors 1 and 2 had higher levels of Ac-tubulin compared with CP- and AM-MSCs. However, the levels of Ac-tubulin in AM-MSCs from donors 3 and 5 were higher than those of the other 2 types of MSCs. Our results revealed that there was tissue-specific heterogeneity among the 3 types of MSCs from different origin tissues of placenta and individual heterogeneity among donors. In future, the pre-selected placenta-derived MSCs with specific biological advantages may improve the curative effect of cell therapy in different situations.
Unusual Complication of a Neglected Growing Skull Fracture
Authors: Kulkarni Akshay Vijay , Dikshit Priyadarshi , Devi B. Indira , Sadashiva Nishanth , Shukla Dhaval , Bhat Dhananjaya I.
Published: March 2021

Introduction: The growing skull fracture (GSF) is a rare complication seen after head injury in infants and young children. It occurs due to a wide skull defect with underlying dural defect and changes in pressure gradients within skull cavity. Neglected cases may develop progressive neurological deficits and complications after second head trauma. Case Discussion: We present a 14-year-old child who developed sudden-onset, diffuse, soft, fluctuant, circumferential swelling of the head after a road traffic accident. He had sustained a head injury at the age of 3-months leading to an asymptomatic soft swelling over the skull which was left untreated. Present CT scan of the brain showed a bony defect with ragged edges and cerebrospinal fluid (CSF) collection in subgaleal space circumferentially. He underwent exploration, duroplasty, and cranioplasty and had a good outcome. Conclusion: Neglected GSF can rupture and cause diffuse subgaleal CSF collection. It should be managed with dural repair and cranioplasty.
Improved Formula for Predicting Hemodialyzability of Intravenous and Oral Drugs
Authors: Murakami Marina , Narita Yuki , Urata Motoki , Ichigi Misato , Nakatani Sakura , Kondo Yuki , Ishitsuka Yoichi , Irie Tetsumi , Hirata Sumio
Published: March 2021

Background: The rate of drug removal by hemodialysis needs to be considered when designing drug dosage regimens for patients on hemodialysis. We previously developed a simplified equation to predict the removal rates of intravenously administered drugs by hemodialysis. Here, we addressed shortcomings of this equation and developed a more accurate equation that can also predict the removal rates of orally administered drugs. Methods: A total of 70 drugs with known pharmacokinetic and physical parameters and drug removal rates that were measured during hemodialysis in clinical cases were randomly assigned at a 4:1 ratio to a training data group or a test data group. A prediction equation was developed by performing stepwise multiple regression analyses using the training data (i.e., the removal rate by hemodialysis) as the objective variable and pharmacokinetic parameters as the explanatory variables. The equation was validated using the test data. Results: Multiple regression analyses revealed that molecular weight (MW), protein binding rate, and fraction excreted unchanged in urine relative to the volume of distribution (Vd) were independently correlated with the drug clearance rate (adjusted coefficient of determination, 0.83; p = 2.2e−16). The following equation was obtained: drug removal rate by hemodialysis (%) = −17.32 × [log (MW)] – 0.39 × [protein binding rate (%)] + 0.06 × [fraction excreted unchanged in urine (%)/Vd (L/kg)] + 83.34. Validation of the equation using the test data showed a very high correlation between predicted and measured reduction rate (R = 0.93, p = 1.87e−6). Mean error was −3.34 (95% confidence interval: −10.03, 3.35), mean absolute error was 9.59, and root mean square error was 16.48. Conclusion: The modified equation derived in this study using pharmacokinetic and physical parameters as variables precisely predicted the removal rates of both intravenous and oral drugs by hemodialysis.
Subcutaneous Allergen-Specific Immunotherapy Is Safe in Pediatric Patients with Allergic Rhinitis
Authors: Pavon-Romero Gandhi F. , Larenas-Linnemann Désirée E. , Xochipa Ruiz Karen Eloisa , Ramirez-Jimenez Fernando , Teran Luis M.
Published: March 2021

Introduction: Subcutaneous allergen-specific immunotherapy (SCIT) is one of the main cornerstones in the treatment of allergic rhinitis in pediatric patients. It has demonstrated symptoms and quality of life improvement, but it is not exempt from adverse reactions (ADVrs). Nevertheless, there are a few reports that have evaluated their safety. Our objective was to evaluate the ADVr to SCIT in pediatric patients. Methods: We reviewed 786 clinical records with SCIT from 2005 to 2018, comparing the clinical characteristics of patients with ADVrs with SCIT versus a group of a similar number of patients who completed SCIT (control group, CG). The analysis of ADVrs was according to the World Allergy Organization (WAO) 2010 grading system by frequency analysis, survival curve, and log rank. Results: Of 786 patients, 106 (13.4%) presented ADVrs, and the patients with ADVr had sensitivity and immunotherapy with at least 2 allergens versus CG p < 0.001, containing a combination of standardized and nonstandardized allergens (p = 0.003). The ADVrs were in the buildup phase (p < 0.001). The survival curve showed that 50% had some reaction at 12 weeks of SCIT. The most frequent ADVr was grade 1 in 73/106 patients (68.8%) and grade 2 in 33/106 (31.1%). The log-rank analysis between the grades of the WAO grading system showed a statistically significant difference (p = 0.02). Conclusions: The SCIT is safe in pediatric patients. The ADVrs are infrequent, grade 1 being the most reported; however, at >12 weeks, the risk of ADVrs that involve 2 organs systems increases.
Postoperative Cognitive Dysfunction and the Protective Effects of Enriched Environment: A Systematic Review
Authors: Hua Momin , Min Jia
Published: March 2021

Background: Currently, the number of individuals who undergo surgery is greatly increased. As a consequence, postoperative cognitive dysfunction (POCD) has gradually gained more attention. Summary: POCD is a perioperative complication requiring sensitive preoperative and postoperative neuropsychiatric tests, and its incidence in both cardiac and noncardiac surgery is high, especially in elderly individuals. Surgical, patient, and anesthetic factors may all lead to the occurrence and development of POCD. The key mechanism of POCD may be the inflammatory response of the central nervous system during surgery, which is similar to that of Alzheimer’s disease (AD). Enriched environment (EE), a factor that can significantly improve and prevent neurodegenerative diseases, may have a beneficial effect on POCD. Key Messages: This review aims to elucidate the mechanism of the occurrence and development of POCD, analyze the possible influence of EE on POCD at the molecular level, and provide a direction for its treatment.
Homogeneously Staining Regions (HSR) in Chromosome 1 of the House Mouse: Synapsis and Recombination at Meiosis
Authors: Torgunakov Nikita Y. , Kizilova Elena A. , Karamysheva Tatyana V. , Malinovskaya Lyubov P. , Bikchurina Tatiana I. , Borodin Pavel M.
Published: March 2021

Amplified sequences constitute a large part of mammalian genomes. A chromosome 1 containing 2 large (up to 50 Mb) homogeneously staining regions (HSRs) separated by a small inverted euchromatic region is present in many natural populations of the house mouse (Mus musculus musculus). The HSRs are composed of a long-range repeat cluster, Sp100-rs, with a repeat length of 100 kb. In order to understand the organization and function of HSRs in meiotic chromosomes, we examined synapsis and recombination in male mice hetero- and homozygous for the HSR-carrying chromosome using FISH with an HSR-specific DNA probe and immunolocalization of the key meiotic proteins. In all homozygous and heterozygous pachytene nuclei, we observed fully synapsed linear homomorphic bivalents 1 marked by the HSR FISH probe. The synaptic adjustment in the heterozygotes was bilateral: the HSR-carrying homolog was shortened and the wild-type homolog was elongated. The adjustment was reversible: desynapsis at diplotene was accompanied by elongation of the HSRs. Immunolocalization of H3K9me2/3 indicated that the HSRs in the meiotic chromosome retained the epigenetic modification typical for C-heterochromatin in somatic cells. MLH1 foci, marking mature recombination nodules, were detected in the proximal HSR band in heterozygotes and in both HSR bands of homozygotes. Unequal crossing over within the long-range repeat cluster can cause variation in size of the HSRs, which has been detected in the natural populations of the house mouse.
Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood
Authors: Aydoğan Metin , Topal Erdem , Uysal Pınar , Acar Hazal Cansu , Cavkaytar Ozlem , Hızlı Demirkale Zeynep , Aydoğmuş Çiğdem , Yakıcı Nalan , Aydemir Sezin , Akkelle Emre , Eser Simsek Işıl , Kaplan Fatih , Arga Mustafa , Yücel Esra , Tugba Cogurlu Müjde , Erdoğan Mehmet Sarper , Tamay Zeynep , Güler Nermin , Yeşil Yakup , Çekiç Sükrü , Sapan Nihat , Cokugras Haluk , Kıykım Ayça , Cigerci Günaydın Nursen , Tuncel Tuba , Orhan Fazıl , Özdemir Öner , Ozdemir Cevdet
Published: March 2021

Background: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. Objective: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. Methods: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. Results: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow’s milk, hen’s eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow’s milk-induced acute urticaria was 92% (95% CI: 81–96%). A history of cow’s milk-induced and/or hen’s egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen’s kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). Conclusion: Cow’s milk, hen’s eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.
Incidence of Cognitive Impairment during Aging in Rural South Africa: Evidence from HAALSI, 2014 to 2019
Authors: Kobayashi Lindsay C. , Farrell Meagan T. , Langa Kenneth M. , Mahlalela Nomsa , Wagner Ryan G. , Berkman Lisa F.
Published: March 2021

Introduction: Despite rapid population aging, there are currently limited data on the incidence of aging-related cognitive impairment in sub-Saharan Africa. We aimed to determine the incidence of cognitive impairment and its distribution across key demographic, social, and health-related factors among older adults in rural South Africa. Methods: Data were from in-person interviews with 3,856 adults aged ≥40 who were free from cognitive impairment at baseline in the population-representative cohort, “Health and Aging in Africa: a Longitudinal Study of an INDEPTH Community in South Africa” (HAALSI), in Agincourt sub-district, Mpumalanga province, South Africa (2014–19). Cognitive impairment was defined as scoring <1.5 standard deviations below the mean of the baseline distribution of orientation and episodic memory scores. Incidence rates and rate ratios for cognitive impairment were estimated according to key demographic, social, and health-related factors, adjusted for age, sex/gender, and country of birth. Results: The incidence of cognitive impairment was 25.7/1,000 person-years (PY; 95% confidence interval [CI]: 23.0–28.8), weighted for mortality (12%) and attrition (6%) over the 3.5-year mean follow-up (range: 1.5–4.8 years). Incidence increased with age, from 8.9/1,000 PY (95% CI: 5.2–16.8) among those aged 40–44 to 93.5/1,000 PY (95% CI: 75.9–116.3) among those aged 80+, and age-specific risks were similar by sex/gender. Incidence was strongly associated with formal education and literacy, as well as marital status, household assets, employment, and alcohol consumption but not with history of smoking, hypertension, stroke, angina, heart attack, diabetes, or prevalent HIV. Conclusions: This study presents some of the first incidence rate estimates for aging-related cognitive impairment in rural South Africa. Social disparities in incident cognitive impairment rates were apparent in patterns similar to those observed in many high-income countries.
Incidence and Risk Factors Affecting Development of Perianal Fistulas after Drainage of Perianal Abscesses
Authors: Khalil Omar Mohammad , Al Ozaibi Labib , Kaiyasah Hadiel M. , Hejazi Nour AlDeen
Published: March 2021

Background: Perianal fistulas can present significant morbidity and detriment to a patient’s quality of life. This study aimed to quantify the incidence of perianal fistulas and attempted to identify any risk factors for their development. Materials and Methods: This retrospective study reviewed all patients who underwent drainage of first-time perianal abscesses in Rashid Hospital from 2014 to 2018. Noncryptoglandular causes of fistula formation were excluded after which incidence and risk factors were investigated. Results and Discussion: A total of 445 records were reviewed of which 131 met the inclusion criteria (103 males and 28 females). The median age of patients was 37 with ranges of 15–85. There was no statistically significant finding relating to gender (p value = 1.00), smoking (p value = 1.00), location of perianal abscess (p value = 0.347), and postoperative antibiotics (p value = 0.694). There was no statistically significant finding relating to patients below or above 40 (p value = 0.846), and logistic regression testing revealed no statistical significance in age relating to development of perianal fistulas. There was a 13.2% increased proportion of nondiabetics to develop perianal fistulas as compared to diabetics (32 vs. 19%), but it was not found to be statistically significant (p value = 0.236). Conclusion: None of the risk factors studied were found to be statistically significant in the development of perianal fistulas after drainage of perianal abscesses and the incidence was found to be 29.8%.
Changes in Clinical and Histological Characteristics of Nasal Polyps in Northern China over the Past 2–3 Decades
Authors: Yu Jiaqi , Xian Mu , Piao Yingshi , Zhang Luo , Wang Chengshuo
Published: March 2021

Introduction: Recent studies have shown that inflammatory patterns of nasal polyps from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) in East Asia have changed over time. However, to date there is a marked lack of similar data for CRSwNP in Northern China. This study thus aimed to assess the changes in the clinical and histological characteristics of CRSwNP patients from Northern China over the past 2–3 decades. Methods: This was a retrospective study, which examined data from 2 groups of 150 CRSwNP patients each, who had undergone endoscopic sinus surgery in Beijing Tongren Hospital from 1993 to 1995 (group A) and from 2015 to 2019 (group B). All relevant data for demographic, clinical, and histological parameters were collected for each patient from the 2 groups and compared for overall changes between the 2 groups. Results: The comorbidity of CRSwNP and asthma increased over time and the cellular phenotype of CRSwNPchanged significantly; in particular, the proportion of eosinophil-dominant CRSwNP increased, lymphocyte-dominant and plasma-dominant CRSwNP decreased significantly, and the proportions of neutrophil-dominant and mixed CRSwNP were not altered. The rate of polyp recurrence increased in CRSwNP but did not in eosinophilic CRSwNP. Smoking and age did not significantly impact the inflammatory patterns of CRSwNP. Conclusions: The inflammatory patterns of CRSwNP patients have changed and comorbidity of asthma significantly increased in CRSwNP patients in Northern China over the past 2–3 decades.
Manic-Depressive Cycles in Bipolar Disorder: Clinical and Treatment Implications
Authors: Teobaldi Elena , Albert Umberto , Di Salvo Gabriele , Mencacci Claudio , Rosso Gianluca , Salvi Virginio , Maina Giuseppe
Published: March 2021

Introduction: Cycle patterns of bipolar disorders (BDs) have been previously shown to be associated with clinical characteristics and response to lithium salts. Here, we evaluated the distribution of different types of manic-depressive cycles in a large sample of patients with BD. The associations between a mania-depression-interval (MDI) course and depression-mania-interval (DMI) course with sociodemographic/clinical factors were also assessed in order to define specific clinical profiles. Methods: In this cross-sectional study, 806 patients with BD admitted to the Psychiatric Unit of San Luigi Gonzaga Hospital in Orbassano and Molinette Hospital in Turin, Italy, were recruited. Patients were grouped according to the following course patterns: MDI, DMI, continuous cycling (CC, <4 episodes/year without intervals), rapid cycling (RC, ≥4 episodes/year), and irregular (IRR) cycling. We compared several sociodemographic and clinical variables in an MDI versus DMI course by means of ANOVA and Pearson χ2 with Bonferroni correction. Results: Bipolar cycles were distributed as follows: 50.2% IRR course, 31.5% MDI course, 16% DMI course, 1.2% CC, and 1% RC. Compared to DMI course, patients with an MDI course were more often men, younger, with an earlier onset, a manic polarity onset, and more lifetime compulsory admissions. They were more frequently treated with lithium and antipsychotics. Patients with a DMI course had older age at diagnosis and at first mood-stabilizer treatment and were more often misdiagnosed with a major depressive disorder. These patients were more commonly treated with anticonvulsants, and they had more frequently failed treatment trials with lithium salts in the past. Conclusion: This study supports the utility of classifying BD according to their course patterns. This classification holds prognostic as well as therapeutic implications.
New Record of Bipolaris cynodontis: An Emerging Human Pathogen Causing Superficial Mycosis in North India
Authors: Sharma Bharti , Nonzom Skarma
Published: March 2021

Superficial mycosis, a common fungal infection affecting people worldwide are prevalent in the tropical and subtropical countries, mostly caused by the dermatophytes but nowadays, there is an increase in the incidence of these infections being caused by non-dermatophytic fungi and yeasts. Among non-dermatophytes, Bipolaris species, usually known to cause diseases in plants, have also emerged as potent human pathogens in the past years. Reports on Bipolaris species associated with clinical human skin samples are rare worldwide with no reports on B. cynodontis as a causal agent of superficial human skin mycoses from India. We report the first case of superficial mycosis caused by B. cynodontis that affected the feet of a 19-year-old female student from Jammu district, Jammu and Kashmir, India. Thus, the causal agent described in the research communication constitutes a new addition to the list of pathogenic non-dermatophytes associated with human skin.
Early Experiences with Triple Immunochemotherapy in Adolescents and Young Adults with High-Risk Fibrolamellar Carcinoma
Authors: Gottlieb Sara , O’Grady Claire , Gliksberg Ariel , Kent Paul
Published: March 2021

Introduction: There are no standard systemic therapies for the treatment of fibrolamellar carcinoma (FLC), as surgery remains the only definitive option. We share our experiences using systemic “triple therapy” (TT) with 5-fluorouracil, interferon, and nivolumab for the treatment of relapsed, refractory, metastatic, or unresectable FLC. Methods: Data from all patients who received TT from May 2018 to July 2020 were reviewed to assess response, survival, and toxicity. Results: A total of 22 patients were treated with TT, of which 14 (median age of 21 years) were evaluable. They received a median of 18 cycles (8–44). At the time of analysis, the median progression-free survival was 9 months (4.5–26), 29% longer than prior to TT, with 5 patients achieving clinical remission, 8 patients stable or improving, and 1 progression. Overall objective response (clinical remission + partial response) was 50% and tumor control rate (clinical remission + partial response + stable disease) was 93%. Two patients withdrew from treatment due to side effects. Discussion/Conclusion: Our early results support TT as a promising medical option to slow disease progression and prolong survival in high-risk patients with FLC. TT can be administered in the outpatient setting and has shown good tolerability. Further longitudinal data is needed to confirm outcomes, especially in patients still early in their treatment.