bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Non-Clinical Determinants of the Effect of Mechanical Thrombectomy and Post-Stroke Functional Status of Patients in Short and Long-Term Follow-Up
Authors: Lasek-Bal Anetta , Binek Łukasz , Żak Amadeusz , Student Sebastian , Krzan Aleksandra , Puz Przemysław , Bal Wiesław , Uchwat Urszula
Published: November 2021

To date, inconsistent results evaluating the effect of parameters on mechanical thrombectomy (MT) outcomes in stroke-patients have been published. This study aimed to identify the key parameters for functional status after MT in stroke-patients in short and long-term follow-up. Method: The study analysis focused on the relevance of selected clinical and non-clinical parameters to the functional status of the patients after MT. Results: 417 stroke-patients (mean age 67.8 ± 13.2 years) were qualified. Atrial fibrillation, and leukocytosis were significant for the neurological status on the first day of stroke (p = 0.036, and p = 0.0004, respectively). The parameters with the strongest effect on the functional status on day 10 were: age (p = 0.009), NIHSS (p = 0.002), hyperglycemia (p = 0.009), the result in TICI (p = 0.046), and first pass effect (p = 0.043). The parameters with the strongest effect on the functional status on day 365 were: age and NIHSS on the first day of stroke (p = 0.0002 and 0.002, respectively). Leukocytosis and the neurological status at baseline were key parameters associated with ICB after MT (p = 0.007 and p = 0.003, respectively). Conclusions: Age and neurological status in the ultra-acute phase of stroke are crucial for the functional status in short and long-term observations of patients treated with mechanical thrombectomy. Atrial fibrillation, hyperglycemia, and inflammatory state are relevant to the short-term post-stroke functional status. First pass effect and the degree of post-interventional reperfusion are important technical parameters to the short-term functional status. Neurological status and white blood count during the acute phase are associated with a high rate of post-procedural intracranial bleeding.
Association of Non-Invasive Positive Pressure Ventilation with Short-Term Clinical Outcomes in Patients Hospitalized for Acute Decompensated Heart Failure
Authors: Yukino Midori , Nagatomo Yuji , Goda Ayumi , Kohno Takashi , Takei Makoto , Nishihata Yosuke , Saji Mike , Toyosaki Yuichi , Nakano Shintaro , Ikegami Yukinori , Shiraishi Yasuyuki , Kohsaka Shun , Adachi Takeshi , Yoshikawa Tsutomu
Published: November 2021

The real-world evidence has been sparse on the impact of non-invasive positive pressure ventilation (NPPV) on the outcomes in acute decompensated heart failure (ADHF) patients. We aim to explore this issue in the prospective multicenter WET-HF registry. Among 3927 patients (77 (67–84) years, male 60%), the NPPV was used in 775 patients (19.7%). The association of NPPV use with in-hospital outcome and length of hospital stay (LOS) was examined by two methods, propensity score (PS) matching and multivariable analysis with adjustment for PS. In these analyses the NPPV group exhibited a lower endotracheal intubation (ETI) rate and a comparable in-hospital mortality, but longer LOS compared to the non-NPPV group. In the stratified analysis, the NPPV group exhibited a significantly lower ETI rate in patients with ischemic etiology, systolic blood pressure (sBP) > 140 mmHg and the Controlling Nutritional Status (CONUT) score ≤ 3, indicating better nutritional status. On the contrary, NPPV use was associated with longer LOS in patients with non-ischemic etiology, sBP < 100 mmHg and CONUT score > 3. In conclusion, NPPV use was associated with a lower incidence of ETI. Particularly, patients with ischemic etiology, high sBP, and better nutritional status might benefit from NPPV use.
Association of microRNA-34a rs2666433 (A/G) Variant with Systemic Lupus Erythematosus in Female Patients: A Case-Control Study
Authors: Ismail Nesreen M. , Toraih Eman A. , Mohammad Mai H. S. , Alshammari Eida M. , Fawzy Manal S.
Published: November 2021

Several microRNAs (miRNAs) are associated with autoimmune disease susceptibility and phenotype, including systemic lupus erythematosus (SLE). We aimed to explore for the first time the role of the miRNA-34a gene (MIR34A) rs2666433A > G variant in SLE risk and severity. A total of 163 adult patients with SLE and matched controls were recruited. Real-Time allelic discrimination PCR was applied for genotyping. Correlation with disease activity and clinic-laboratory data was done. The rs2666433 variant conferred protection against SLE development under heterozygous [A/G vs. G/G; OR = 0.57, 95%CI = 0.34–0.95], homozygous [A/A vs. G/G; OR = 0.52, 95%CI = 0.29–0.94], dominant [A/G + A/A vs. GG; OR = 0.55, 95%CI = 0.35–0.88], and log-additive [OR = 0.71, 95%CI = 0.53–0.95] models. Data stratification by sex revealed a significant association with SLE development in female participants under heterozygous/homozygous models (p-interaction = 0.004). There was no clear demarcation between SLE patients carrying different genotypes regarding the disease activity index or patients stratified according to lupus nephritis. Enrichment analysis confirmed the implication of MIR34A in the SLE pathway by targeting several genes related to SLE etiopathology. In conclusion, although the MIR34A rs2666433 variant conferred protection against developing SLE disease in the study population, it showed no association with disease activity. Replication studies in other populations are warranted.
Decreased Thyroxine Levels during rhGH Therapy in Children with Growth Hormone Deficiency
Authors: Witkowska-Sędek Ewelina , Kucharska Anna Małgorzata , Rumińska Małgorzata , Paluchowska Monika , Pyrżak Beata
Published: November 2021

Background: Hypothyroidism in children leads to growth retardation. However, there is some evidence that recombinant human growth hormone (rhGH) therapy could suppress thyroid function. The most common observation in rhGH-treated patients is a decrease in thyroxine levels, which is reported as transient, but the studies in the field are inconsistent. We aimed to evaluate thyroid function in initially euthyroid children with idiopathic isolated GH deficiency during long-term rhGH therapy and to determine who is at a higher risk of thyroid function alterations during the therapy. Methods: The study group consisted of 101 children treated with rhGH for at least three years. Serum TSH and fT4 levels were determined at baseline, after the first six months and after each full year of therapy. The associations between changes in thyroid hormone levels during rhGH therapy and GH deficit, insulin-like growth factor-1 levels and growth response were investigated. Results: A significant decrease in fT4 levels (p = 0.01) was found as early as after the first six months of rhGH therapy. This effect persisted in the subsequent years of treatment without any significant changes in TSH values and tended to be rhGH dose related. Children with a greater fT4 decrease after the initiation of rhGH therapy were older, had higher bone age and responded to that therapy worse than children with lower fT4 changes. Conclusions: Our study revealed a long-term decrease in fT4 levels during rhGH therapy in initially euthyroid GHD children. The decrease in fT4 levels was associated with a lower growth response to rhGH therapy.
A Study on the Genetics of Primary Ciliary Dyskinesia
Authors: Alsamri Mohammed T. , Alabdouli Amnah , Iram Durdana , Alkalbani Alia M. , Almarzooqi Ayesha S. , Souid Abdul-Kader , Vijayan Ranjit
Published: November 2021

Primary ciliary dyskinesia (PCD) is a poorly understood disorder. It is primarily autosomal recessive and is prevalent in tribal communities of the United Arab Emirates due to consanguineous marriages. This retrospective study aimed to assess the pathogenicity of the genetic variants of PCD in indigenous patients with significant clinical respiratory problems. Pathogenicity scores of variants obtained from the chart review were consolidated using the Ensembl Variant Effect Predictor. The multidimensional dataset of scores was clustered into three groups based on their pathogenicity. Sequence alignment and the Jensen–Shannon Divergence (JSD) were generated to evaluate the amino acid conservation at the site of the variation. One-hundred and twelve variants of 28 genes linked to PCD were identified in 66 patients. Twenty-two variants were double heterozygous, two triple heterozygous, and seven homozygous. Of the thirteen novel variants, two, c.11839 + 1G > A in dynein, axonemal, heavy chain 11 (DNAH11) and p.Lys92Trpfs in dynein, axonemal, intermediate chain 1 (DNAI1) were associated with dextrocardia with situs inversus, and one, p.Gly21Val in coiled-coil domain-containing protein 40 (CCDC40), with absent inner dynein arms. Homozygous C1orf127:p.Arg113Ter (rs558323413) was also associated with laterality defects in two related patients. The majority of variants were missense involving conserved residues with a median JSD score of 0.747. Homology models of two deleterious variants in the stalk of DNAH11, p.Gly3102Asp and p.Leu3127Arg, revealed structural importance of the conserved glycine and leucine. These results define potentially damaging PCD variants in the region. Future studies, however, are needed to fully comprehend the genetic underpinnings of PCD.
Stent Selection for Primary Angioplasty and Outcomes in the Era of Potent Antiplatelets. Data from the Multicenter Randomized Prague-18 Trial
Authors: Hlinomaz Ota , Motovska Zuzana , Knot Jiri , Miklik Roman , Sabbah Mahmoud , Hromadka Milan , Varvarovsky Ivo , Dusek Jaroslav , Svoboda Michal , Tousek Frantisek , Majtan Bohumil , Simek Stanislav , Branny Marian , Jarkovský Jiří
Published: November 2021

Drug-eluting stents (DES) are the recommended stents for primary percutaneous coronary intervention (PCI). This study aimed to determine why interventional cardiologists used non-DES and how it influenced patient prognoses. The efficacy and safety outcomes of the different stents were also compared in patients treated with either prasugrel or ticagrelor. Of the PRAGUE-18 study patients, 749 (67.4%) were treated with DES, 296 (26.6%) with bare-metal stents (BMS), and 66 (5.9%) with bioabsorbable vascular scaffold/stents (BVS) between 2013 and 2016. Cardiogenic shock at presentation, left main coronary artery disease, especially as the culprit lesion, and right coronary artery stenosis were the reasons for selecting a BMS. The incidence of the primary composite net-clinical endpoint (EP) (death, nonfatal myocardial infarction, stroke, serious bleeding, or revascularization) at seven days was 2.5% vs. 6.3% and 3.0% in the DES, vs. with BMS and BVS, respectively (HR 2.7; 95% CI 1.419–5.15, p = 0.002 for BMS vs. DES and 1.25 (0.29–5.39) p = 0.76 for BVS vs. DES). Patients with BMS were at higher risk of death at 30 days (HR 2.20; 95% CI 1.01–4.76; for BMS vs. DES, p = 0.045) and at one year (HR 2.1; 95% CI 1.19–3.69; p = 0.01); they also had a higher composite of cardiac death, reinfarction, and stroke (HR 1.66; 95% CI 1.0–2.74; p = 0.047) at one year. BMS were associated with a significantly higher rate of primary EP whether treated with prasugrel or ticagrelor. In conclusion, patients with the highest initial risk profile were preferably treated with BMS over BVS. BMS were associated with a significantly higher rate of cardiovascular events whether treated with prasugrel or ticagrelor.
A Decade of Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: Does the Outcome Improve?
Authors: Lin Cheng-Hsien , Shih Yu-Hsuan , Chen Tsung-Chih , Chou Cheng-Wei , Hsu Chiann-Yi , Teng Chieh-Lin Jerry
Published: November 2021

To investigate the potential treatment evolution and outcome improvement, we retrospectively compared clinical characteristics, therapeutic strategies, treatment responses, and overall survival (OS) in patients diagnosed and treated with lymphoma-associated HLH between 2004–2012 (n = 30) and 2013–2021 (n = 26). Our study showed that the clinical characteristics of lymphoma-associated HLH did not substantially change over the past two decades. However, more patients diagnosed in 2013–2021 were tested for Epstein–Barr virus than those diagnosed in 2004–2012 (69.3% vs. 33.3%; p = 0.021). In addition, Eastern Cooperative Oncology Group performance status 3–4 (hazard ratio (HR): 5.38; 95% confidence intervals (CI): 2.49–11.61; p < 0.001) and jaundice (HR: 2.91; 95% CI: 1.37–6.18; p = 0.006) were poor prognostic factors for lymphoma-associated HLH. With a comparable response rate of lymphoma treatment, patients treated in 2013–2021 had a numerically greater median OS than those treated in 2004–2012 (23.6 ± 19.8 vs. 9.7 ± 4.5 months). However, the difference was not statistically significant (p = 0.334). In conclusion, early diagnosis and tailored treatments that balance efficacy and adverse events remain the key to obtaining a better outcome in lymphoma-associated HLH.
Gender Disparities in Vascular Access and One-Year Mortality among Incident Hemodialysis Patients: An Epidemiological Study in Lazio Region, Italy
Authors: Angelici Laura , Marino Claudia , Umbro Ilaria , Bossola Maurizio , Calandrini Enrico , Tazza Luigi , Agabiti Nera , Davoli Marina ,   on behalf of the Regional Registry Dialysis and Transplant Lazio Region
Published: November 2021

(1) Background: Interest in gender disparities in epidemiology, clinical features, prognosis and health care in chronic kidney disease patients is increasing. Aims of the study were to evaluate the association between gender and vascular access (arteriovenous fistula (AVF) or central venous catheter (CVC)) used at the start of hemodialysis (HD) and to investigate the association between gender and 1-year mortality. (2) Methods: The study includes 9068 adult chronic HD patients (64.7% males) registered in the Lazio Regional Dialysis Register (January 2008–December 2018). Multivariable logistic regression models were used to investigate the associations between gender and type of vascular access (AVF vs. CVC) and between gender and 1-year mortality. Interactions between gender and socio-demographic and clinical variables were tested adding the interaction terms in the final model. (3) Results: Females were older, had lower educational level and lower rate of self-sufficiency compared to males. Overall, CVC was used in 51.2% of patients. Females were less likely to use AVF for HD initiation than males. 1354 out of 8215 (16.5%) individuals died at the end of the follow-up period. Interaction term between gender and vascular access was significant in the adjusted model. From stratified analyses by vascular access, OR female vs. male (AVF) = 0.65; 95% CI 0.48–0.87 and OR female vs. male (CVC) = 0.88; 95% CI 0.75–1.04 were found. (4) Conclusions: This prospective population-based cohort study in a large Italian Region showed that in females starting chronic HD AVF was less common respect to men. The better 1-year survival of females is more evident among those women with AVF. Reducing gender disparity in access to AVF represents a key point in the management of HD patients.
A Retrospective Analysis of Clinical Outcome and Predictive Factors for Responders with Knee Osteoarthritis to a Single Injection of Leukocyte-Poor Platelet-Rich Plasma
Authors: Kikuchi Naoya , Yoshioka Tomokazu , Arai Norihito , Sugaya Hisashi , Hyodo Kojiro , Taniguchi Yu , Okuno Kosuke , Kanamori Akihiro , Yamazaki Masashi
Published: November 2021

Although various platelet-rich plasma (PRP) kits are commercially available, the efficacy of these kits for knee osteoarthritis (KOA) has not been fully investigated. This study aimed to investigate the short-term results of leukocyte-poor PRP (LP-PRP) and the factors that contribute to its efficacy. We retrospectively reviewed 124 patients with KOA who were treated with LP-PRP. White blood cell (WBC) and platelet counts in the whole blood and the LP-PRP were measured. KOA severity was assessed using radiography. Clinical evaluation was performed both prior to injection and after an average of 3.3 weeks after the injection using the Japanese Knee Osteoarthritis Measure (JKOM). Responders were defined based on the JKOM. The contributing factors for responders were examined using a multivariate logistic analysis. The responder rate was 58.1% and the contributing factors for responders were a higher visual analog scale score before injection, WBC count in whole blood, and platelet concentration ratio of LP-PRP. The LP-PRP improved the clinical scores in the short term. Certain patient characteristics before injection and the concentration ratio of LP-PRP may be predictors of its efficacy; these may provide clues for elucidating which components of LP-PRP act on KOA pathologies.
The Role of Multimodality Imaging in Athlete’s Heart Diagnosis: Current Status and Future Directions
Authors: D’Andrea Antonello , Sperlongano Simona , Russo Vincenzo , D’Ascenzi Flavio , Benfari Giovanni , Renon Francesca , Palermi Stefano , Ilardi Federica , Giallauria Francesco , Limongelli Giuseppe , Bossone Eduardo
Published: November 2021

“Athlete’s heart” is a spectrum of morphological and functional changes which occur in the heart of people who practice physical activity. When athlete’s heart occurs with its most marked expression, it may overlap with a differential diagnosis with certain structural cardiac diseases, including cardiomyopathies, valvular diseases, aortopathies, myocarditis, and coronary artery anomalies. Identifying the underlying cardiac is essential to reduce the potential for sudden cardiac death. For this purpose, a spectrum of imaging modalities, including rest and exercise stress echocardiography, speckle tracking echocardiography, cardiac magnetic resonance, computed tomography, and nuclear scintigraphy, can be undertaken. The objective of this review article is to provide to the clinician a practical step-by-step approach, aiming at distinguishing between extreme physiology and structural cardiac disease during the athlete’s cardiovascular evaluation.
Lymphaticovenous Anastomosis for Age-Related Lymphedema
Authors: Yoshida Shuhei , Koshima Isao , Imai Hirofumi , Roh Solji , Mese Toshiro , Uchiki Toshio , Sasaki Ayano , Nagamatsu Shogo
Published: November 2021

Introduction: Primary lymphedema is usually caused by intrinsic disruption or genetic damage to the lymphatics but may also be the result of age-related deterioration of the lymphatics. The aims of this study were to determine the characteristics of age-related lymphedema and to assess the effectiveness of lymphaticovenous anastomosis (LVA) in its treatment. Methods: Eighty-six patients with primary lymphedema affecting 150 lower limbs were divided into three groups according to whether the age of onset was younger than 35 years, 35–64 years, or 65 years or older. Indocyanine green (ICG) lymphography was performed, followed by LVA surgery. ICG lymphography images were visually classified according to whether the pattern was linear, low enhancement (LE), distal dermal backflow (dDB), or extended dermal backflow (eDB). The lower extremity lymphedema (LEL) index score was calculated before and after LVA. Lymphatic vessel diameter and detection rates were also recorded. Results: In the ≥65 group, the lymphedema was bilateral in 54 patients and unilateral in 1 patient. There was statistically significant deterioration in the LEL index score with progression from the linear, LE, dDB through to the eDB pattern in the ≥65 group. The lymphatic vessel diameter was significantly greater in the ≥65 group. The rate of improvement was highest in the ≥65 group. Conclusion: Age-related lymphedema was bilateral and deterioration started distally. The lymphatic vessels in patients with age-related lymphedema tended to be ectatic, which is advantageous for LVA and may increase the improvement rate.
Methodologies for the Determination of Blood Alpha1 Antitrypsin Levels: A Systematic Review
Authors: Ruiz-Duque Borja , Bañuls Lucía , Reinoso-Arija Rocio , Carrasco-Hernandez Laura , Caballero-Eraso Candelaria , Dasí Francisco , Lopez-Campos José Luis
Published: November 2021

Background: The study of hematic concentrations of alpha1 antitrypsin (AAT) is currently one step in the diagnosis of AAT deficiency. To try to clarify the relevance of the laboratory techniques, we carried out a systematic review of the literature. Methods: Studies evaluating the quantification of AAT in peripheral blood were searched in PubMed in July 2021. The selection criteria included (1) any type of study design that included a quantification of AAT in peripheral blood; (2) studies written in English or Spanish; (3) studies evaluating human beings; and (4) studies involving adults. Results: Out of 207 studies, the most frequently used techniques were nephelometry (43.9%), followed by ELISA (19.8%) and turbidimetry (13.5%). Altogether, 182 (87.9%) cases expressed their results in units of gram, while 16 (7.7%) articles expressed them in units of mole. Only 2.9% articles referred to the standard used, 43.5% articles indicated the commercial kit used, and 36.2% indicated the analyzer used. Conclusions: The technical aspects of these determinations are not always reported in the literature. Journals should be attentive to these technical requirements and ensure that they are included in the works in which AAT is determined in order to ensure a correct interpretation of the study findings.
Risk Factors for Spine Reoperation and Joint Replacement Surgeries after Short-Segment Lumbar Spinal Surgeries for Lumbar Degenerative Disc Disease: A Population-Based Cohort Study
Authors: Wu Meng-Huang , Wu Christopher , Lin Jiann-Her , Chen Li-Ying , Lee Ching-Yu , Huang Tsung-Jen , Hsieh Yi-Chen , Chien Li-Nien
Published: November 2021

Background: Short-segment lumbar spinal surgery is the most performed procedure for treatment of degenerative disc disease. However, population-based data regarding reoperation and joint replacement surgeries after short-segment lumbar spinal surgery is limited. Methods: The study was a retrospective cohort design using the Taiwan National Health Insurance Research Database for data collection. Patients selected were diagnosed with lumbar degenerative disc disease and undergone lumbar discectomy surgery between 2002 and 2013. The Kaplan–Meier method was used to estimate the incidence of 1-year spine reoperation and joint replacement surgeries, and the Cox proportional hazard regression was used to examine risk factors associated with the outcomes of interest. Results: A total of 90,105 patients were included. Incidences of 1-year spine reoperation and joint replacement surgeries for the hip and knee were 0.27, 0.04, and 0.04 per 100 people/month. Compared to fusion with the fixation group, fusion without fixation and the non-fusion group had higher risks of spine reoperation. Risk factors associated with spine reoperation included fusion without fixation, non-fusion surgery, age ≥ 45 years old, male gender, diabetes, a Charlson Comorbidity Index = 0, lowest social economic status, and steroid use history. Spine surgeries were not risk factors for joint replacement surgeries. Conclusions: Non-fusion surgery and spinal fusion without fixation had higher risks for spine reoperation. Spine surgeries did not increase the risk for joint replacement surgeries.
Prostate Artery Embolization—Review of Indications, Patient Selection, Techniques and Results
Authors: Naidu Sailendra G. , Narayanan Harish , Saini Gia , Segaran Nicole , Alzubaidi Sadeer J. , Patel Indravadan J. , Oklu Rahmi
Published: November 2021

Lower urinary tract symptoms (LUTS) due to benign prostatic hypertrophy (BPH) are a very common problem in men ranging from mild urinary symptoms to recurrent urinary tract infections or renal failure. Numerous treatment options are available ranging from conservative medical therapies to more invasive surgical options. Prostate artery embolization (PAE) has emerged as a novel treatment option for this common problem with clinical efficacy comparable to the current surgical gold standard, transurethral resection of the prostate (TURP). PAE offers fewer complications and side effects without a need for general anesthesia or hospitalization. This review discusses the indications for prostate artery embolization in addition to LUTS, patient evaluation in patients with LUTS, PAE technique and clinical results, with an emphasis on efficacy and safety.
Gender Differences in the Impact of New-Onset Atrial Fibrillation on Long-Term Risk of Ischemic Stroke after Acute Myocardial Infarction
Authors: Yi Jeong-Eun , Seo Suk-Min , Lim Sungmin , Choo Eun-Ho , Choi Ik-Jun , Lee Kwan-Yong , Hwang Byung-Hee , Kim Chan-Joon , Park Mahn-Won , Kim Dong-Bin , Her Sung-Ho , Lee Jong-Min , Park Chul-Soo , Kim Pum-Joon , Kim Hee-Yeol , Yoo Ki-Dong , Jeon Doo-Soo , Chung Wook-Sung , Jeong Myung-Ho , Ahn Youngkeun , Chang Kiyuk
Published: November 2021

Background: Atrial fibrillation (AF) has been identified as a major risk factor for mortality after acute coronary syndrome (ACS). However, the long-term risk of ischemic stroke associated with new-onset atrial fibrillation (NOAF) in ACS remains controversial, and its gender-specific association is unknown. Methods: We analyzed the data of 10,137 ACS survivors included in a multicenter, prospective registry for Korean patients with acute myocardial infarction (AMI) between January 2004 and August 2014. Subjects were categorized into three groups (non-AF vs. NOAF vs. previous AF) based on medical history and electrocardiographic evidence of AF, either at admission or during hospitalization. Results: Among the total study population (72.3% men), 370 patients (3.6%) had NOAF and 130 (1.3%) had previous AF. During a median follow-up of 61 months (interquartile range, 38.8 to 89.3 months), 245 (2.4%) patients (218 (2.3%) non-AF vs. 15 (4.1%) NOAF vs. 12 (9.2%) previous AF, p < 0.001) experienced ischemic stroke. After adjustment for confounding variables, both NOAF (adjusted hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.09–3.24, p = 0.024) and previous AF (adjusted HR 4.00, 95% CI 2.03–7.87, p < 0.001), along with older age, diabetes, current smoker, and previous stroke were independent risk factors of ischemic stroke. In the gender-stratified analysis, men with previous AF but not NOAF had a significantly higher risk of ischemic stroke (adjusted HR 4.14, 95% CI 1.79–9.55, p = 0.001) than those without AF. In women, NOAF (adjusted HR 2.54, 95% CI 1.21–5.35, p = 0.014) as well as previous AF (adjusted HR 3.72, 95% CI 1.16–11.96, p = 0.028) was a strong predictor of ischemic stroke, and the predictive value was comparable to that of previous AF among patients with a CHA2DS2-VASc score ≥ 2. Conclusions: Both NOAF and previous AF were associated with ischemic stroke after AMI, but the impact of NOAF as a risk factor of ischemic stroke was significant only in women.
Progressive Comparison of Density Assessment of Alveolar Bone Graft in Patients with Unilateral and Bilateral Cleft
Authors: Chen Pin-Ru , Lin Yu-Ching , Pai Betty Chien-Jung , Tseng Hsiao-Jung , Lo Lun-Jou , Chou Pang-Yun
Published: November 2021

(1) Background: Continuing to observe the grafted bone mineral density (BMD) is essential to ensure the success of alveolar bone grafting (ABG) in patients with cleft lip and palate. This study elaborates on three methods that can be used to evaluate the progressive BMD. (2) Methods: Forty patients with unilateral or bilateral clefts receiving ABG were enrolled. Cone beam computed tomography (CBCT) scans were taken at 6 months (T1) and 2 years (T2) postoperatively. In CBCT, measurements were obtained on three different planes using the circle located 1 mm from the adjacent teeth (Method A), the largest circle within the defect (Method B), or the central circle with a diameter of 2 mm (Method C). The BMD was the average density of the three planes and was adjusted by pogonion density. Bland–Altman plots were used to evaluate the agreement of each method. Inter-rater reliability was confirmed by the intraclass correlation coefficient (ICC). (3) Results: For Method A, B, and C, the mean-adjusted BMD (BMD/pogonion density, BMDa) was 17.44%, 17.88%, and 17.69%, respectively, at T1 (p = 0.495), and 22.51%, 22.87%, and 22.74%, respectively, at T2 (p = 0.690); the density enhancement rates were 40.54%, 38.92%, and 43.15% (p = 0.382). Significant differences between the BMDa at T1 and T2 were observed (p < 0.001, <0.001, and 0.001, for Method A, B, and C, respectively). The volume of the grafted tissue remained stable during T1 and T2, and no significant correlation between density enhancement rate and volume loss was observed. (4) Conclusions: A significant increase in the BMD of grafted tissue was observed in the 2-year postoperative follow-up. The three methods for measuring BMDa via CBCT can be applied in post-ABG evaluations.
Amplified Vasodilatation within the Referred Pain Zone of Trigger Points Is Characteristic of Gluteal Syndrome—A Type of Nociplastic Pain Mimicking Sciatica
Authors: Skorupska Elzbieta , Dybek Tomasz , Rychlik Michał , Jokiel Marta , Zawadziński Jarosław , Dobrakowski Paweł
Published: November 2021

Gluteal syndrome (GS) mimicking sciatica is a new disease that has been recently recognized and included in the International Classification of Diseases, 11th Revision. The present study examines nociplastic pain involvement in GS and sciatica patients using a new Skorupska protocol (SP) test that provokes amplified vasodilatation in the area of expected muscle-referred pain. A positive test is confirmed if there is (i) a development of autonomic referred pain (AURP) and (ii) an increase in the delta of average temperature (Δ₸°) > 0.3 °C at the end of the stimulation and during the observation SP phases. Chronic GS (n = 20) and sciatica (n = 30) patients were examined. The SP test confirmed muscle-referred pain for (i) all GS patients with 90.6% positive thermograms (Δ₸° 0.6 ± 0.8 °C; maximum AURP 8.9 ± 13.6% (both p < 0.05)) and (ii) those sciatica (n = 8) patients who reported pain sensation during the test with 20.6% positive thermograms (Δ₸° 0.7 ± 0.7 °C; maximum AURP 15.1 ± 17.8% (both p < 0.05)). The remaining sciatica (n = 22) patients did not report pain during the test and presented a Δ₸° decrease and the AURP size below 1%. Conclusion: Amplified vasodilatation suggesting nociplastic pain involvement was confirmed for all GS and sciatica patients who reported painful sensations in the zone typical for gluteus minimus referred pain during the test.
Quantitative Evaluation of Soil Structure and Strain in Three Dimensions under Shear Using X-ray Computed Tomography Image Analysis
Authors: Nohara Shintaro , Mukunoki Toshifumi
Published: November 2021

The objective of this study is to quantitatively evaluate the soil structure behavior when under shear stress to understand the mechanism of shear zone formation using a micro-focus X-ray computed tomography (CT) scanner to visualize the internal samples without causing disturbance. A new image-analysis method was proposed to systematically evaluate the particle length and direction by fitting the particle as an ellipsoid. Subsequently, a direct shear experiment was conducted on soil materials, and shear band was scanned using a micro-focus X-ray CT scanner. After validating the proposed method, the soil structure was evaluated in the shear zone via image analysis on the CT images. Furthermore, the strain inside the specimen was evaluated using digital image correlation. The results showed that a partial change in the particle direction occurred when the volume expansion inside the shear zone exceeded the peak. In addition, the width of the shear zone was ~7.1 times the median grain size of the sand used; however, the region exhibiting a change in the direction of the particles was narrow and confined to the vicinity of the shear plane.
The Relationship between Alexithymia, Dysmorphic Concern, and Exercise Addiction: The Moderating Effect of Self-Esteem
Authors: Gori Alessio , Topino Eleonora , Pucci Caterina , Griffiths Mark D.
Published: November 2021

As with other addictions, exercise addiction can severely impact individuals’ lives and have significant psychophysical consequences. Consequently, the study of the mechanisms involved in this psychopathological condition has great clinical and practical relevance. Therefore, the goal of the present study was to explore the risk factors and protective factors for exercise addiction, with a particular focus on the roles of alexithymia, body image concerns, and self-esteem. A sample of 288 regular exercisers (mean age = 28.35 years, SD = 8.26; 72% females, 18% males) completed the Exercise Addiction Inventory, 20-Item Toronto Alexithymia Scale, Body Image Concern Inventory, and Rosenberg Self-Esteem Scale. Data were analyzed by implementing a moderated mediation model. Results showed a significant and positive association between alexithymia and exercise addiction, totally mediated by body image concerns. Furthermore, self-esteem showed a relevant moderating effect, such that at high levels of self-esteem the effect of alexithymia on body image concerns became insignificant. Such data have important implications, highlighting some core variables on which it might be useful to keep a focus in order to elaborate tailored interventions, from both preventive and treatment perspectives.
Biomarkers in Ovarian Pathology: From Screening to Diagnosis. Review of the Literature
Authors: Elorriaga Miguel Ángel , Neyro José Luis , Mieza Jon , Cristóbal Ignacio , Llueca Antoni
Published: November 2021

Background: Ovarian cancer has a low incidence, but high mortality due to a habitual diagnosis in advanced cancer stages. Currently, used biomarkers have good sensitivity, but low specificity. Aim: To determine the usefulness of the biomarkers and algorithms used up to now in the screening, diagnosis, response to treatments and identification of recurrence in patients with ovarian masses. Methodology: Systematic search of publications in English in the Medline-PubMed database with the terms: “biomarkers”, “tumour”, “tumour biomarkers”, “marker”, “tumour marker”, “ovarian cancer”, “ovarian”, “Neoplasms”, “cancer”, CA-125 Antigen; Human Epididymis-specific Protein E4; Risk of Malignancy Index (RMI); Risk of Ovarian Malignancy Algorithm (ROMA); Ovarian Neoplasms. Original articles, clinical trials, reviews, systematic reviews and meta-analyses, published between January 2000 and November 2020, were selected to determine the usefulness (among others) of CA 125 and HE4 antigen in ovarian cancer. Results: Finally, 39 transcendental publications were selected to write this article to determine the usefulness of tumour markers and algorithms in ovarian cancer. Conclusions: The usefulness of the tumour markers antigen CA125 and antigen HE4 individually or as a basis for decision-making algorithms has low specificity; however, there is little evidence that confirms their usefulness as markers in ovarian cancer screening.
Mechanisms Involved in Microglial-Interceded Alzheimer’s Disease and Nanocarrier-Based Treatment Approaches
Authors: Md Shadab , Alhakamy Nabil , Alfaleh Mohamed , Afzal Obaid , Altamimi Abdulmalik , Iqubal Ashif , Shaik Rasheed
Published: November 2021

Alzheimer’s disease (AD) is a common neurodegenerative disorder accountable for dementia and cognitive dysfunction. The etiology of AD is complex and multifactorial in origin. The formation and deposition of amyloid-beta (Aβ), hyperphosphorylated tau protein, neuroinflammation, persistent oxidative stress, and alteration in signaling pathways have been extensively explored among the various etiological hallmarks. However, more recently, the immunogenic regulation of AD has been identified, and macroglial activation is considered a limiting factor in its etiological cascade. Macroglial activation causes neuroinflammation via modulation of the NLRP3/NF-kB/p38 MAPKs pathway and is also involved in tau pathology via modulation of the GSK-3β/p38 MAPK pathways. Additionally, microglial activation contributes to the discrete release of neurotransmitters and an altered neuronal synaptic plasticity. Therefore, activated microglial cells appear to be an emerging target for managing and treating AD. This review article discussed the pathology of microglial activation in AD and the role of various nanocarrier-based anti-Alzeihmenr’s therapeutic approaches that can either reverse or inhibit this activation. Thus, as a targeted drug delivery system, nanocarrier approaches could emerge as a novel means to overcome existing AD therapy limitations.
A Cost–Consequence Analysis of Preemptive SLCO1B1 Testing for Statin Myopathy Risk Compared to Usual Care
Authors: Brunette Charles A. , Dong Olivia M. , Vassy Jason L. , Danowski Morgan E. , Alexander Nicholas , Antwi Ashley A. , Christensen Kurt D.
Published: November 2021

There is a well-validated association between SLCO1B1 (rs4149056) and statin-associated muscle symptoms (SAMS). Preemptive SLCO1B1 pharmacogenetic (PGx) testing may diminish the incidence of SAMS by identifying individuals with increased genetic risk before statin initiation. Despite its potential clinical application, the cost implications of SLCO1B1 testing are largely unknown. We conducted a cost–consequence analysis of preemptive SLCO1B1 testing (PGx+) versus usual care (PGx−) among Veteran patients enrolled in the Integrating Pharmacogenetics in Clinical Care (I-PICC) Study. The assessment was conducted using a health system perspective and 12-month time horizon. Incremental costs of SLCO1B1 testing and downstream medical care were estimated using data from the U.S. Department of Veterans Affairs’ Managerial Cost Accounting System. A decision analytic model was also developed to model 1-month cost and SAMS-related outcomes in a hypothetical cohort of 10,000 Veteran patients, where all patients were initiated on simvastatin. Over 12 months, 13.5% of PGx+ (26/193) and 11.2% of PGx− (24/215) participants in the I-PICC Study were prescribed Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline-concordant statins (Δ2.9%, 95% CI −4.0% to 10.0%). Differences in mean per-patient costs for lipid therapy prescriptions, including statins, for PGx+ compared to PGx− participants were not statistically significant (Δ USD 9.53, 95% CI −0.86 to 22.80 USD). Differences in per-patient costs attributable to the intervention, including PGx testing, lipid-lowering prescriptions, SAMS, laboratory and imaging expenses, and primary care and cardiology services, were also non-significant (Δ− USD 1004, 95% CI −2684 to 1009 USD). In the hypothetical cohort, SLCO1B1-informed statin therapy averted 109 myalgias and 3 myopathies at 1-month follow up. Fewer statin discontinuations (78 vs. 109) were also observed, but the SLCO1B1 testing strategy was 96 USD more costly per patient compared to no testing (124 vs. 28 USD). The implementation of SLCO1B1 testing resulted in small, non-significant increases in the proportion of patients receiving CPIC-concordant statin prescriptions within a real-world primary care context, diminished the incidence of SAMS, and reduced statin discontinuations in a hypothetical cohort of 10,000 patients. Despite these effects, SLCO1B1 testing administered as a standalone test did not result in lower per-patient health care costs at 1 month or over 1 year of treatment. The inclusion of SLCO1B1, among other well-validated pharmacogenes, into preemptive panel-based testing strategies may provide a better balance of clinical benefit and cost.
Vital Pulp Therapy in Permanent Teeth with Irreversible Pulpitis Caused by Caries: A Prospective Cohort Study
Authors: Guan Xiaoxu , Zhou Yi , Yang Qingxia , Zhu Tianer , Chen Xuepeng , Deng Shuli , Zhang Denghui
Published: November 2021

Background: When a tooth is diagnosed with irreversible pulpitis, root canal therapy (RCT) is generally performed to completely remove pulp tissue, which might lead to a higher risk of loss of vascularity, and teeth being more prone to fracture. Vital pulp therapy (VPT) is a personalized method of treating irreversible pulpitis, which conforms to the trend of minimally invasive endodontics. The remaining vital pulp could promote the physiological development of the roots of young permanent teeth with incomplete apical foramen. However, clear guidelines for VPT indication are still missing. Objective: This prospective cohort study evaluated the outcomes of vital pulp therapy (VPT) using iRoot BP Plus (Innovative Bioceramix Inc, Vancouver, BC, Canada) in permanent teeth of 6- to 20-year-old patients with irreversible pulpitis caused by caries and analyzed the preoperative factors affecting VPT prognosis. Methods: Fifty-nine permanent teeth in 59 patients with irreversible pulpitis caused by caries were treated with VPT using iRoot BP Plus. All patients received VPT under a standardized protocol. After informed consent, teeth were isolated with a dental dam, then operators performed VPT with iRoot BP Plus and restored the teeth with composite resin or stainless steel crown. Patients were postoperatively recalled after 3, 6 and 12 months and then recalled annually. Successful cases were defined as successful in both clinical and radiographic evaluations. A statistical analysis was performed using the Fisher exact test, and the level of significant difference was p < 0.05. Results: After 6–36 months of follow-up, a total of 57 teeth from 57 patients were accessible for evaluation. The mean age of subjects was 11.75 ± 3.81 years. The overall clinical and radiographic success rate of VPT was 91.2% (52/57). With an observation time of one year or more, the success rate was 90.5% (38/42). All the symptoms and physical examination findings showed no significant effect on VPT prognosis (p > 0.05) using a binary logistic regression model. Conclusions: Permanent teeth in 6- to 20-year-old patients diagnosed as irreversible pulpitis caused by caries can be successfully treated with VPT using iRoot BP Plus.
The 2-Year Leakage Index and Quantitative Microaneurysm Results of the RECOVERY Study: Quantitative Ultra-Widefield Findings in Proliferative Diabetic Retinopathy Treated with Intravitreal Aflibercept
Authors: Babiuch Amy S. , Wykoff Charles C. , Yordi Sari , Yu Hannah , Srivastava Sunil K. , Hu Ming , Le Thuy K. , Lunasco Leina , Reese Jamie , Nittala Muneeswar G. , Sadda SriniVas R. , Ehlers Justis P.
Published: November 2021

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized to receive either 2 mg IAI every 4 weeks (Arm 1) or every 12 weeks (Arm 2) through Year 1. After Year 1, Arm 1 switched to quarterly IAI and Arm 2 to monthly IAI through Year 2. By Year 2, the Arm 1 leakage index decreased by 43% from Baseline (p = 0.03) but increased by 59% from Year 1 (p = 0.04). Arm 2 decreased by 61% from Baseline (p = 0.008) and by 31% from Year 1 (p = 0.12). Both cohorts exhibited a significant decline in MAs from Baseline to Year 2 (871 to 410; p < 0.001; 776 to 207; p < 0.001, respectively). Subjects with an improved leakage and MA count showed a more significant improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Moreover, central subfield thickness (CST) was positively associated with changes in the leakage index. In conclusion, the leakage index and MA counts significantly improved from Baseline following IAI treatment, and monthly injections provided a more rapid and sustained reduction in these parameters compared with quarterly injections.
Relationship between Cataract Surgery and Mortality in Elderly Patients with Cataract: Nationwide Population-Based Cohort Study in South Korea
Authors: Kim Jae-Yong , Chung Ho-Seok , Lee Ji-Sung , Lee Hun , Tchah Hungwon
Published: November 2021

We aimed to investigate the relationship between cataract surgery and all-cause and cause-specific mortality in Korean elderly patients with cataract using the Korean National Health Insurance Service-Senior cohort database. Elderly patients (≥60 years) diagnosed with cataract from 2002 through 2012 were included. The baseline characteristics included demographics and systemic and ocular comorbidities. Adjusted Cox regression models with time-varying covariates for cataract surgery were used to assess the relationship between cataract surgery and mortality. The study cohort included 241,062 patients, of whom 127,941 were in the cataract surgery group and 113,121 were in the cataract diagnosis group. The incidence of all-cause mortality was 3.62 deaths/100 person-years and 3.19 deaths/100 person-years in the cataract surgery and cataract diagnosis groups, respectively. Cataract surgery was associated with a decreased hazard of all-cause mortality after adjusting for demographics as well as systemic and ocular comorbidities (hazard ratio (HR), 0.93; p < 0.001). A protective association was noted between cataract surgery and mortality from vascular (HR, 0.92; p < 0.001) or neurologic (HR, 0.64; p < 0.001) causes. Patients with cataract who were 85 years of age and older, women, those who had lower income, and a Charlson comorbidity index score of 5 or more, or those without glaucoma revealed the largest reductions in mortality hazards resulting from cataract surgery.
Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence
Authors: Tariq Fomaz , Khan Walizeb , Ahmad Washaakh , Riaz Syeda Kiran , Khan Mahvish , Sherwani Subuhi , Haque Shafiul , Malik Muhammad Faraz Arshad , Iftikhar Muhammad Jahangir , Khan Saif , Haq Farhan
Published: November 2021

Dysregulated immune response significantly affects hepatocellular carcinoma’s (HCC) prognosis. Human Leukocyte Antigens are key in devising immune responses against HCC. Here, we investigated how HLAs modulate HCC development at the transcriptomic level. RNA-seq data of 576 patients from two independent cohorts was retrieved. The clinicopathological relevance of all HLA genes was investigated using Fisher-Exact, correlation, and Kaplan–Meier and cox regression survival tests. Clustering of ~800 immune-related genes against HLAs was completed using a ward-agglomerative method. Networks were generated using 40 HLA associated unique genes and hub genes were investigated. HLAs including HLA-DMA, HLA-DMB, HLA-DOA and HLA-DRB6 were associated with delayed recurrence in both discovery (204 HCC cases) and validation (372 HCC cases) cohorts. Clustering analyses revealed 40 genes associated with these four HLAs in both cohorts. A set of seven genes (NCF4, TYROBP, LCP2, ZAP70, PTPRC, FYN and WAS) was found co-expressed at gene–gene interaction level in both cohorts. Furthermore, survival analysis revealed seven HLA-linked genes as predictors of delayed recurrence. Multivariate analysis also predicted that mean expression of 7-gene is an independent predictor of delayed recurrence in both cohorts. We conclude that the expression of 7-gene signature may lead to improved patient prognosis. Further studies are required for consideration in clinical practice.