bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in Ischemia-Modified Albumin and Pregnancy-Associated Plasma Protein-A in COVID-19 Patients
Authors: Sanchez Belén G. , Gasalla Jose M. , Sánchez-Chapado Manuel , Bort Alicia , Diaz-Laviada Inés
Published: December 2021

This study was undertaken due to the urgent need to explore reliable biomarkers for early SARS-CoV-2 infection. We performed a retrospective study analyzing the serum levels of the cardiovascular biomarkers IL-6, TNF-α, N-terminal pro-B natriuretic peptide, cardiac troponin T (cTnT), ischemia-modified albumin (IMA) and pregnancy-associated plasma protein-A (PAPP-A) in 84 patients with COVID-19.Patients were divided into three groups according to their RT-qPCR and IgG values: acute infection (n = 35), early infection (n = 25) or control subjects (n = 24). Levels of biomarkers were analyzed in patient serum samples using commercially available ELISA kits. Results showed a significant increase in IMA and PAPP-A levels in the early infected patients. Moreover, multivariate analysis and receiver operating characteristic (ROC) curve showed that IMA and PAPP-A had excellent discrimination value for the early stage of COVID-19. For IMA, the area under the ROC curve (AUC) had a value of 0.94 (95% confidence interval (CI): 0.881–0.999). Likewise, the serum level of PAPP-A was significantly higher in patients with early infection than in the control subjects (AUC = 0.801 (95% CI: 0.673–0.929)). The combined use of IMA and PAPP-A enhanced the sensitivity for total SARS-CoV-2-infected patients to 93%. These results suggest that the increased levels of PAPP-A and IMA shed light on underlying mechanisms of COVID-19 physiopathology and might be used as efficient biomarkers with high sensitivity and specificity for the early stage of COVID-19. Importantly, when monitoring pregnancy and cardiovascular diseases using PAPP-A or IMA levels, a SARS-CoV-2 infection should be discarded for proper interpretation of the results.
Clinical Significance of Distant Metastasis-Free Survival (DMFS) in Melanoma: A Narrative Review from Adjuvant Clinical Trials
Authors: Amabile Simone , Roccuzzo Gabriele , Pala Valentina , Tonella Luca , Rubatto Marco , Merli Martina , Fava Paolo , Ribero Simone , Fierro Maria Teresa , Queirolo Paola , Quaglino Pietro
Published: December 2021

Cutaneous melanoma is the most dangerous skin cancer, with high death rates in advanced stages. To assess the impact of each treatment on patient outcomes, most studies use relapse-free survival (RFS) as a primary endpoint and distant metastasis-free survival (DMFS) as a secondary endpoint. The aim of this narrative review of the main adjuvant studies for resected stage III/IV melanoma, with a specific focus on DMFS, is to evaluate DMFS trends and their potential association with RFS, identify which treatments are possibly associated with better outcomes in terms of DMFS and their potential predictive factors, and discuss DMFS trends in terms of patient management in daily practice. We outline the impact of each available treatment option on DMFS and RFS according to the years of follow-up and compare data from different studies. Overall, the trends of DMFS closely follow those of RFS, with most patients relapsing at visceral rather than regional sites. As it captures the burden of patients who develop distant relapse, DMFS could be considered a primary endpoint, in addition to RFS, in adjuvant trials, identifying patients whose relapse is associated with a worse prognosis and who may need further systemic treatment.
Prediction of Different Eye Diseases Based on Fundus Photography via Deep Transfer Learning
Authors: Guo Chen , Yu Minzhong , Li Jing
Published: December 2021

With recent advancements in machine learning, especially in deep learning, the prediction of eye diseases based on fundus photography using deep convolutional neural networks (DCNNs) has attracted great attention. However, studies focusing on identifying the right disease among several candidates, which is a better approximation of clinical diagnosis in practice comparing with the case that aims to distinguish one particular eye disease from normal controls, are limited. The performance of existing algorithms for multi-class classification of fundus images is at most mediocre. Moreover, in many studies consisting of different eye diseases, labeled images are quite limited mainly due to privacy concern of patients. In this case, it is infeasible to train huge DCNNs, which usually have millions of parameters. To address these challenges, we propose to utilize a lightweight deep learning architecture called MobileNetV2 and transfer learning to distinguish four common eye diseases, including Glaucoma, Maculopathy, Pathological Myopia, and Retinitis Pigmentosa, from normal controls using a small training data. We also apply a visualization approach to highlight the loci that are most related to the disease labels to make the model more explainable. The highlighted area chosen by the algorithm itself may give some hints for further fundus image studies. Our experimental results show that our system achieves an average accuracy of 96.2%, sensitivity of 90.4%, and specificity of 97.6% on the test data via five independent runs, and outperforms two other deep learning-based algorithms both in terms of accuracy and efficiency.
Hemodialysis Effect on the Composition of the Eye Fluid of Cataract Patients
Authors: Dolar-Szczasny Joanna , Flieger Jolanta , Kowalska Beata , Majerek Dariusz , Tatarczak-Michalewska Małgorzata , Zakrocka Izabela , Załuska Wojciech , Rejdak Robert
Published: December 2021

Numerous reports have proven that dialysis patients experience disturbances in the levels of elements in biological fluids. Disturbances in the homeostasis of essential elements or the appearance of highly toxic elements are serious problems also in clinical ophthalmology. The purpose of this study was to investigate the influence of hemodialysis (HD) on the elemental composition of anterior chamber aqueous humor (AH) in patients undergoing cataract surgery. The study involved 22 patients. The control group enrolled 16 patients (age 75.68 ± 9.67, female 54.55%, male 45.45%) with cataract and normal kidney function (control), and the second group included six patients (age 70.33 ± 12.74, female 33.33%, male 66.67%) with cataract undergoing HD treatment. The elements quantification was established using an inductively coupled plasma optical emission spectrometer (ICP-MS). In the eye fluid of dialysis patients, there were increased levels of manganese (Mn) and mercury (Hg) and decreased levels of vanadium (V) and zinc (Zn). In addition, a statistically significant increase in the Hg/Zn and Hg/selenium (Se) ratios and a lowering of the iron (Fe)/Mn ratio were observed in the studied group in comparison to the control. The obtained results indicated the need for Zn and Se supplementation in order to eliminate the hazards caused by Hg toxicity. A lower level of V in the eye fluid of dialysis patients may have a positive effect on maintaining a calcium and phosphorus homeostasis. Our study gives a deep insight into changes of elements concentrations in AH induced by HD.
Photodynamic Therapy in the Treatment of Vulvar Lichen Sclerosus: A Systematic Review of the Literature
Authors: Gerkowicz Agnieszka , Szczepanik-Kułak Paulina , Krasowska Dorota
Published: December 2021

Vulvar lichen sclerosus (VLS) is a chronic inflammatory disease involving the genital skin and mucous membrane. Patients exhibit focal atrophy and destructive scarring, with an increased risk of malignant transformation. Due to objective symptoms as well as subjective complaints, patients with VLS experience emotional distress, lowered mood, and sexual dysfunction, which is reflected in impaired health-related quality of life. Thus, the necessity of implementing appropriate therapy at the earliest possible stage of the disease in order to avoid serious complications is highlighted. We presented the systematic review of available literature, performed with MEDLINE, Cinahl, Central, Scopus, and Web of Science databases. We identified a total of twenty relevant studies which indicate that photodynamic therapy (PDT) is a valuable therapeutic modality in the treatment of VLS.
Risk Factors Associated with Refractory Epilepsy in Patients with Tuberous Sclerosis Complex: A Systematic Review
Authors: Miszewska Dominika , Sugalska Monika , Jóźwiak Sergiusz
Published: December 2021

Background: Epilepsy affects 70–90% of patients with tuberous sclerosis complex (TSC). In one-third of them, the seizures become refractory to treatment. Drug-resistant epilepsy (DRE) carries a significant educational, social, cognitive, and economic burden. Therefore, determining risk factors that increase the odds of refractory seizures is needed. We reviewed current data on risk factors associated with DRE in patients with tuberous sclerosis. Methods: The review was performed according to the PRISMA guidelines. Embase, Cochrane Library, MEDLINE, and ClinicalTrial.gov databases were searched. Only full-text journal articles on patients with TSC which defined risk factors related to DRE were included. Results: Twenty articles were identified, with a cohort size between 6 and 1546. Seven studies were prospective. Three factors appear to significantly increase DRE risk: TSC2 mutation, infantile spasms, and a high number of cortical tubers. Conclusions: A proper MRI and EEG monitoring, along with genetic testing, and close observation of individuals with early onset of seizures, allow identification of the patients at risk of DRE.
Clinical Impact of Hormone Replacement Therapy on Atrial Fibrillation in Postmenopausal Women: A Nationwide Cohort Study
Authors: Lee Jaehoon , Kim Yuntae , Park Hyunji , Kim Changsoo , Cho Sihyun , Kim Jongyoun
Published: December 2021

Individuals with atrial fibrillation (AF), especially women, have an increased risk of stroke and death. Although hormone replacement therapy (HRT) is widely used in postmenopausal women, the association between HRT use and AF risk is unclear. We aimed to investigate the association between various types of HRT and AF. This was a population-based retrospective cohort study from The Korean National Health Insurance Service-National Sample Cohort (2004–2015). Participants were aged 45–60 years and were free from cardiovascular disease and AF at baseline. Overall, 13,452 (64.03%) women had never received HRT, 5671 (26.99%) had received HRT, and 1885 (8.98%) were currently receiving HRT. In multivariable analysis, the relative hazards for AF were significantly higher among current users (p < 0.001) and lower among past users (p = 0.069). Current users—except those using estradiol-only HRT—had significantly elevated AF risk. Among past users, only estradiol plus progestin HRT users had a reduced AF risk after adjusting for covariates (p = 0.027). Ongoing HRT posed an increased risk of AF. The degree of risk varied based on the specific type of estrogen and progestins co-administration. These findings indicate that, with respect to AF risk, oral estradiol-containing HRT is superior to HRT containing oral conjugated equine estrogen or tibolone.
Lymphocytopenia and Anti-CD38 Directed Treatment Impact the Serological SARS-CoV-2 Response after Prime Boost Vaccination in Patients with Multiple Myeloma
Authors: Ghandili Susanne , Schönlein Martin , Wiessner Christian , Becher Heiko , Lütgehetmann Marc , Brehm Thomas Theo , Schulze zur Wiesch Julian , Bokemeyer Carsten , Sinn Marianne , Weisel Katja C. , Leypoldt Lisa B.
Published: December 2021

Even though several SARS-CoV-2 vaccines have shown high effectiveness in the prevention of COVID-19 in healthy subjects, vaccination response in patients with plasma-cell-related disorders (PCD) remains widely unknown. Here, we report on an analysis describing the serological response after prime-boost SARS-CoV-2 vaccination in PCD patients, as compared to a healthy control group, and on possible influencing factors of serological responses. Blood samples were analyzed for the presence of quantitative anti-SARS-CoV-2 spike RBD Ig. A total of 82 patients were included; 67 received mRNA-, eight vector-based and four heterologous vaccinations. SARS-CoV-2 antibody titers (SP-AbT) were assessed in a mean of 23 days (SD ± 11 days) after the first and in a mean 21 days (SD ± 9) after prime-boost vaccination. A positive SP-AbT was detected in 31.9% of PCD patients after the first vaccination, and in 88.9% (44/49) after prime-boost vaccination, which was significantly less likely than that in the control group (100%, 78/78) (p = 0.008). Furthermore, we have been able to validate our previously suggested threshold of 30 CD19+ B lymphocytes/µL as being predictive for SP-AbT development. Despite anti-CD38 directed therapy, quadruplet treatment, higher age and missing deep remission, which correlated negatively with SP-AbT appearance, SP-AbT formation is possible in a majority of myeloma patients after prime-boost vaccination.
Sex Differences in Incidence, Clinical Characteristics and Outcomes in Children and Young Adults Hospitalized for Clinically Suspected Myocarditis in the Last Ten Years—Data from the MYO-PL Nationwide Database
Authors: Ozierański Krzysztof , Tymińska Agata , Skwarek Aleksandra , Kruk Marcin , Koń Beata , Biliński Jarosław , Opolski Grzegorz , Grabowski Marcin
Published: December 2021

There is a widespread lack of systematic knowledge about myocarditis in children and young adults in European populations. The MYO-PL nationwide study aimed to evaluate sex differences in the incidence, clinical characteristics, management and outcomes of all young patients with a clinical diagnosis of myocarditis, hospitalized in the last ten years. The study involved data (from the only public healthcare insurer in Poland) of all (n = 3659) patients aged 0–20 years hospitalized for myocarditis in the years 2011–2019. We assessed clinical characteristics, management and five-year outcomes. Males comprised 75.4% of the study population. The standardized incidence rate of myocarditis increased over the last ten years and was, on average, 7.8 and 2.5 (in males and females, respectively). It was the highest (19.5) in males aged 16–20 years. The highest rates of hospital admissions occurred from late autumn to early spring. Most myocarditis-directed diagnostic procedures, including laboratory tests, echocardiography, coronary angiography, cardiac magnetic resonance and endomyocardial biopsy, were performed in a low number of patients, particularly in females. Most patients required rehospitalization for cardiovascular reasons. The results of this large epidemiological study showed an increasing incidence of myocarditis hospitalizations in young patients over last ten years and that it was sex-, age- and season-dependent. Survival in young patients with myocarditis was age- and sex-related and usually it was worse than in the national population. The general management of myocarditis requires significant improvement.
An Underestimated Toxicity Radiation-Induced Hypothyroidism in Patients Multimodally Treated for Breast Cancer
Authors: Mireștean Camil Ciprian , Iancu Roxana Irina , Iancu Dragoș Petru Teodor
Published: December 2021

Radiation therapy is part of the therapeutic arsenal for breast cancer, whether it is adjuvant treatment after lumpectomy or radical mastectomy, or it is used as a palliative option in the case of metastatic or recurrent disease. Significant advances in diagnostic and therapeutic stratification of breast cancers have significantly prolonged survival, even in the metastatic stage. Exposure of patients during the course of the disease in a multidisciplinary therapeutic approach including chemotherapy, hormone therapy, targeted anti-HER therapies or CDK4/6 inhibitors had led to improved survival but with the price of additional toxicity. Among them, hypothyroidism is a well-known consequence of external radiation therapy, especially in the case of cervical region irradiation, including supraclavicular and infra-clavicular nodal levels. In this situation, the thyroid gland is considered as an organ at risk (OAR) and receives a significant dose of radiation. Subclinical hypothyroidism is a common endocrine disorder characterized by elevated TSH levels with normal levels of FT4 (free T4) and FT3 (free T3), and as a late effect, primary hypothyroidism is one of the late effects that significantly affects the quality of life for patients with breast cancer receiving multimodal treatment. Hypothyroidism has a significant impact on quality of life, most often occurring as late clinical toxicity, secondary to thyroid irradiation at doses between 30 and 70 Gy. Dose-volume parameters of irradiation, gland function at the beginning of the treatment and associated systemic therapies may be factors that alter thyroid radio-sensitivity and affect thyroid gland tolerance. In the case of head and neck tumor pathology, in which doses of >50 Gy are routinely used, the thyroid gland is generally considered as an OAR, the rate of radio-induced hypothyroidism being estimated at rates of between 20% and 52%. For breast cancer, the thyroid is often neglected in terms of dosimetry protection, the rate of late dysfunction being 6–21%.
A Historical Cohort in Kidney Transplantation: 55-Year Follow-Up of 72 HLA-Identical, Donor-Recipient Pairs
Authors: Shaw Brian I. , Villani Vincenzo , Kesseli Samuel J. , Nobuhara Chloe , Samoylova Mariya L. , Moris Dimitrios , Collins Bradley H. , McElroy Lisa M. , Poh Melissa , Knechtle Stuart J. , Barbas Andrew S. , Seigler Hilliard F.
Published: December 2021

The impact of HLA matching on graft survival has been well characterized in renal transplantation, with a higher degree of matching associated with superior graft survival. Additionally, living donor grafts are known to confer superior survival compared to those from deceased donors. The purpose of this study is to report our multi-decade institutional experience and outcomes for patients who received HLA-identical living donor grafts, which represent the most favorable scenario in kidney transplantation. We conducted a retrospective analysis of these graft recipients performed at a Duke University Medical Center between the years of 1965 and 2002. The recipients demonstrated excellent graft and patient survival outcomes, superior to a contemporary cohort, with median patient and graft survival of 24.2 and 30.9 years, respectively, among Duke recipients vs. 16.1 and 16.0 years in a cohort derived from national data. This study offers a broad perspective on the importance of HLA matching and graft type, and demonstrates a historical best-case-scenario in renal transplantation.
Angioedema Caused by Drugs That Prevent the Degradation of Vasoactive Peptides: A Pharmacovigilance Database Study
Authors: Noguchi Yoshihiro , Murayama Azusa , Esaki Hiroki , Sugioka Mayuko , Koyama Aisa , Tachi Tomoya , Teramachi Hitomi
Published: December 2021

Angioedema results from the decreased degradation of vasoactive peptides such as substance P and bradykinin. In this study, we sought to clarify whether dipeptidyl peptidase-4 (DPP-4) and angiotensin-converting enzyme (ACE) inhibitors that suppress the degradation of substance P and bradykinin are involved in angioedema onset. We calculated information coefficients (ICs) by performing a disproportionality analysis to evaluate DPP-4/ACE inhibitor-induced angioedema using the Japanese Adverse Drug Event Report (JADER) database. No angioedema signals were detected for DPP-4 inhibitors; however, a signal was detected for ACE inhibitors (IC: 2.42, 95% confidence interval (CI): 2.19 to 2.65). Of the patients treated with DPP-4 inhibitors, four developed drug-induced angioedema in combination with ACE inhibitors, and all were taking vildagliptin. Signals were detected for enalapril (IC: 2.39, 95% CI: 2.06 to 2.71), imidapril (IC: 2.83, 95% CI: 2.38 to 3.27), lisinopril (IC: 2.28, 95% CI: 1.55 to 3.00), temocapril (IC: 1.35, 95% CI: 0.29 to 2.40), and trandolapril (IC: 1.57, 95% CI: 0.19 to 2.95). Both inhibitors inhibited the degradation of substance P and bradykinin and were thus expected to cause angioedema. However, no signal of angioedema was detected with the DPP-4 inhibitors, in contrast to some ACE inhibitors. This study found that ACE inhibitors and DPP-4 inhibitors, which inhibit the degradation of substance P and bradykinin, tended to have different effects on the onset of angioedema in clinical practice.
Changes in Thyroid Hormone Signaling Mediate Cardiac Dysfunction in the Tg197 Mouse Model of Arthritis: Potential Therapeutic Implications
Authors: Ntari Lydia , Mantzouratou Polyxeni , Katsaouni Athanasia , Pantos Constantinos , Kollias George , Mourouzis Iordanis
Published: December 2021

Background Rheumatoid Arthritis (RA) patients show a higher risk of heart failure. The present study investigated possible causes of cardiac dysfunction related to thyroid hormone (TH) signaling in a RA mouse model. Methods A TNF-driven mouse model of RA[TghuTNF (Tg197)] was used. Cardiac function was evaluated by echocardiography. SERCA2a and phospholamban protein levels in left ventricle (LV) tissue, thyroid hormone levels in serum, TH receptors in LV and TH-related kinase signaling pathways were measured. T3 hormone was administered in female Tg197 mice. Results We show LV and atrial dilatation with systolic dysfunction in Tg197 animals, accompanied by downregulated SERCA2a. We suggest an interaction of pro-inflammatory and thyroid hormone signaling indicated by increased p38 MAPK and downregulation of TRβ1 receptor in Tg197 hearts. Interestingly, female Tg197 mice showed a worse cardiac phenotype related to reduced T3 levels and Akt activation. T3 supplementation increased Akt activation, restored SERCA2a expression and improved cardiac function in female Tg197 mice. Conclusions TNF overexpression of Tg197 mice results in cardiac dysfunction via p38 MAPK activation and downregulation of TRβ1. Gender-specific reduction in T3 levels could cause the worse cardiac phenotype observed in female mice, while T3 administration improves cardiac function and calcium handling via modified Akt activation.
Aetiology of Heart Failure, Rather than Sex, Determines Reverse LV Remodelling Response to CRT
Authors: Said Fatema , ter Maaten Jozine M. , Martens Pieter , Vernooy Kevin , Meine Mathias , Allaart Cornelis P. , Geelhoed Bastiaan , Vos Marc A. , Cramer Maarten J. , van Gelder Isabelle C. , Mullens Wilfried , Rienstra Michiel , Maass Alexander H.
Published: December 2021

Introduction: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF). Women appear to respond differently to CRT, yet it remains unclear whether this is inherent to the female sex itself, or due to other patient characteristics. In this study, we aimed to investigate sex differences in response to CRT. Methods: This is a post-hoc analysis of a prospective, multicenter study (MARC) in the Netherlands, studying HFrEF patients with an indication for CRT according to the guidelines (n = 240). Primary outcome measures are left ventricular ejection fraction (LVEF) and left ventricular end systolic volume (LVESV) at 6 months follow-up. Results were validated in an independent retrospective Belgian cohort (n = 818). Results: In the MARC cohort 39% were women, and in the Belgian cohort 32% were women. In the MARC cohort, 70% of the women were responders (defined as >15% decrease in LVESV) at 6 months, compared to 55% of men (p = 0.040) (79% vs. 67% in the Belgian cohort, p = 0.002). Women showed a greater decrease in LVESV %, LVESV indexed to body surface area (BSA) %, and increase in LVEF (all p < 0.05). In regression analysis, after adjustment for BSA and etiology, female sex was no longer associated with change in LVESV % and LVESV indexed to BSA % and LVEF % (p > 0.05 for all). Results were comparable in the Belgian cohort. Conclusions: Women showed a greater echocardiographic response to CRT at 6 months follow-up. However, after adjustment for BSA and ischemic etiology, no differences were found in LV-function measures or survival, suggesting that non-ischemic etiology is responsible for greater response rates in women treated with CRT.
Dysautonomia and Implications for Anosmia in Long COVID-19 Disease
Authors: Vallée Alexandre
Published: December 2021

Long COVID-19 patients often reported anosmia as one of the predominant persisting symptoms. Recent findings have shown that anosmia is associated with neurological dysregulations. However, the involvement of the autonomic nervous system (ANS), which can aggregate all the long COVID-19 neurological symptoms, including anosmia, has not received much attention in the literature. Dysautonomia is characterized by the failure of the activities of components in the ANS. Long COVID-19 anosmia fatigue could result from damage to olfactory sensory neurons, leading to an augmentation in the resistance to cerebrospinal fluid outflow by the cribriform plate, and further causing congestion of the glymphatic system with subsequent toxic build-up in the brain. Studies have shown that anosmia was an important neurologic symptom described in long COVID-19 in association with potential COVID-19 neurotropism. SARS-CoV-2 can either travel via peripheral blood vessels causing endothelial dysfunction, triggering coagulation cascade and multiple organ dysfunction, or reach the systemic circulation and take a different route to the blood–brain barrier, damaging the blood–brain barrier and leading to neuroinflammation and neuronal excitotoxicity. SARS-CoV-2 entry via the olfactory epithelium and the increase in the expression of TMPRSS2 with ACE2 facilitates SARS-CoV-2 neurotropism and then dysautonomia in long COVID-19 patients. Due to this effect, patients with anosmia persisting 3 months after COVID-19 diagnosis showed extensive destruction of the olfactory epithelium. Persistent anosmia observed among long COVID-19 patients may be involved by a cascade of effects generated by dysautonomia leading to ACE2 antibodies enhancing a persistent immune activation.
Clinical Spectrum of Schistosomiasis: An Update
Authors: Carbonell Cristina , Rodríguez-Alonso Beatriz , López-Bernús Amparo , Almeida Hugo , Galindo-Pérez Inmaculada , Velasco-Tirado Virginia , Marcos Miguel , Pardo-Lledías Javier , Belhassen-García Moncef
Published: December 2021

Schistosomiasis is a helminthic infection and one of the neglected tropical diseases (NTDs). It is caused by blood flukes of the genus Schistosoma. It is an important public health problem, particularly in poverty-stricken areas, especially those within the tropics and subtropics. It is estimated that at least 236 million people worldwide are infected, 90% of them in sub-Saharan Africa, and that this disease causes approximately 300,000 deaths annually. The clinical manifestations are varied and affect practically all organs. There are substantial differences in the clinical presentation, depending on the phase and clinical form of schistosomiasis in which it occurs. Schistosomiasis can remain undiagnosed for a long period of time, with secondary clinical lesion. Here, we review the clinical profile of schistosomiasis. This information may aid in the development of more efficacious treatments and improved disease prognosis.
Comparative Risk of Bleeding of Anticoagulant Therapy with Vitamin K Antagonists (VKAs) and with Non-Vitamin K Antagonists in Patients Undergoing Dental Surgery
Authors: Manfredini Mattia , Poli Pier Paolo , Creminelli Luca , Porro Alberto , Maiorana Carlo , Beretta Mario
Published: December 2021

Objectives: A wide variety of approaches have been proposed to manage anticoagulant drugs in patients undergoing dental surgery; vitamin K antagonists and novel direct oral anticoagulants have been used. The present study aims to explore the existing evidence concerning the management of patients in anticoagulant therapy undergoing oral surgery procedures and to give suggestions related to peri- and post-operative measures. Materials and methods: A comprehensive search of databases was conducted to identify studies that evaluated the relationship between direct oral anticoagulants and dental procedures. The present scoping review was realized in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The publications varied from randomized controlled trials (RCT) to cohort trials. Only articles written in English language and published between 2000 to 2020 were screened. The studies were included if discussing the management of a patient in anticoagulant therapy (warfarin or direct oral anticoagulants) scheduled for tooth extraction. Results: 33 studies were selected and included in the qualitative review. Nineteen considered anticoagulant therapy with warfarin, six considered anticoagulant therapy with new oral anticoagulants and eight compared patients taking warfarin with patients taking direct oral anticoagulants. Conclusions: No case of extractive surgery should alter the posology of the drug: thromboembolic risks derived from discontinuation are heavier than hemorrhagic risks. Clinical relevance: direct oral anticoagulants are safer in terms of bleeding and manageability and bleeding episodes are manageable with local hemostatic measures.
Prediction Models for Successful Sperm Retrieval in Patients with Non-Obstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: Is There Any Room for Further Studies?
Authors: Caroppo Ettore , Colpi Giovanni Maria
Published: December 2021

Several prediction models for successful sperm retrieval (SSR) in patients with azoospermia due to spermatogenic dysfunction (also termed non-obstructive azoospermia—NOA) have been developed and published in the past years, however their resulting prediction accuracy has never been strong enough to translate their results in the clinical practice. This notwithstanding, the number of prediction models being proposed in this field is growing. We have reviewed the available evidence and found that, although patients with complete AZFc deletion or a history of cryptorchidism may have better probability of SSR compared to those with idiopathic NOA, no clinical or laboratory marker is able to determine whether a patient with NOA should or should not undergo microdissection testicular sperm extraction (mTESE) to have his testicular sperm retrieved. Further research is warranted to confirm the utility of evaluating the expression of noncoding RNAs in the seminal plasma, to individuate patients with NOA with higher probability of SSR.
Arch-Support Induced Changes in Foot-Ankle Coordination in Young Males with Flatfoot during Unplanned Gait Termination
Authors: Cen Xuanzhen , Gao Lidong , Yang Meimei , Liang Minjun , Bíró István , Gu Yaodong
Published: December 2021

Objective: The efficacy of arch orthoses in posture adjustment and joint coordination improvement during steady-state gait is well documented; however, the biomechanical changes of gait sub-tasks caused by arch support (AS), especially during gait termination, are poorly understood. Hence, this study aimed to investigate how the acute arch-supporting intervention affects foot–ankle coordination and coordination variability (CV) in individuals with flatfoot during unplanned gait termination (UGT). Methods: Twenty-five male patients with flatfoot were selected as subjects participated in this AS manipulation study. A motion capture system was used for the collection of the metatarsophalangeal joint (MPJ) and ankle kinematics during UGT. MPJ-Ankle coordination and CV were quantified using an optimized vector coding technique during the three sub-phases of UGT. A paired-sample t-test from the one-dimensional statistical parametric mapping of one-dimensional was applied to examine the data significance. Results: Significant differences for the joint kinematics between non-arch-support (NAS) and AS were exhibited only in the MPJ transverse plane during the middle and later periods of UGT (p = 0.04–0.026). Frontal plane MPJ-ankle coordination under AS during stimulus delay significantly decreased from 177.16 ± 27.41° to 157.75 ± 32.54° compared with under NAS (p = 0.026); however, the coordination pattern had not changed. Moreover, no significant difference was found in the coupling angle variability between NAS and AS in three planes during sub-phases of UGT (all p > 0.5). Conclusions: The detailed intrinsic characteristic of AS induced acute changes in lower extremity segment coordination in patients with mild flatfoot has been recorded. This dataset on foot-ankle coordination characteristics during UGT is essential for explaining foot function and injury prediction concerning AS manipulation. Further studies are expected to reflect lower limb inter-joint coordination during gait termination through the long-term effects of AS orthoses.
Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I
Authors: Mirea Andrada , Shelby Elena-Silvia , Axente Mihaela , Badina Mihaela , Padure Liliana , Leanca Madalina , Dima Vlad , Sporea Corina
Published: December 2021

Background: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting on the SMN2 gene, is intrathecally administered all life long, while onasemnogene abeparvovec-xioi, a gene therapy, is administered intravenously only once. Both therapies have proven efficacy, with best outcomes obtained when administered presymptomatically. In recent years, disease-modifying therapies such as nusinersen and onasemnogene abeparvovec-xioi have changed the natural history of SMA. Methods: We observed seven SMA type I patients, who received both therapies. We compared their motor function trajectories, ventilation hours and cough assist sessions to a control group of patients who received one therapy, in order to investigate whether combination therapy may be more effective than a single intervention alone. Results: Patients who received both therapies, compared to the monotherapy cohort, had the same motor function trajectory. Moreover, it was observed that the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment. Conclusions: Our results suggest that early treatment is more important than combined therapy.
Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma—A Prospective Report
Authors: Bongiolatti Stefano , Mazzoni Francesca , Salimbene Ottavia , Caliman Enrico , Ammatuna Carlo , Comin Camilla E. , Antonuzzo Lorenzo , Voltolini Luca
Published: December 2021

Malignant pleural mesothelioma (MPM) is an aggressive disease with poor prognosis and the current treatment for early-stage MPM is based on a multimodality therapy regimen involving platinum-based chemotherapy preceding or following surgery. To enhance the cytoreductive role of surgery, some peri- or intra-operative intracavitary treatments have been developed, such as hyperthermic chemotherapy, but long-term results are weak. The aim of this study was to report the post-operative results and mid-term outcomes of our multimodal intention-to-treat pathway, including induction chemotherapy, followed by surgery and Hyperthermic Intraoperative THOracic Chemotherapy (HITHOC) in the treatment of early-stage epithelioid MPM. Since 2017, stage I or II epithelioid MPM patients have been inserted in a surgery-based multimodal approach comprising platinum-based induction chemotherapy, followed by pleurectomy and decortication (P/D) and HITHOC with cisplatin. The Kaplan–Meier method was used to estimate overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). During the study period, n = 65 patients affected by MPM were evaluated by our institutional Multidisciplinary Tumour Board; n = 12 patients with stage I-II who had no progression after induction chemotherapy underwent P/D and HITHOC. Post-operative mortality was 0, and complications developed in n = 7 (58.3%) patients. The median estimated OS was 31 months with a 1-year and 3-year OS of 100% and 55%, respectively. The median PFS was 26 months with 92% of a 1-year PFS, whereas DFS was 19 months with a 1-year DFS rate of 83%. The multimodal treatment of early-stage epithelioid MPM, including induction chemotherapy followed by P/D and HITHOC, was well tolerated and feasible with promising mid-term oncological results.
Influence of Spine Curvature on the Efficacy of Transcutaneous Lumbar Spinal Cord Stimulation
Authors: Binder Veronika E. , Hofstoetter Ursula S. , Rienmüller Anna , Száva Zoltán , Krenn Matthias J. , Minassian Karen , Danner Simon M.
Published: December 2021

Transcutaneous spinal cord stimulation is a non-invasive method for neuromodulation of sensorimotor function. Its main mechanism of action results from the activation of afferent fibers in the posterior roots—the same structures as targeted by epidural stimulation. Here, we investigated the influence of sagittal spine alignment on the capacity of the surface-electrode-based stimulation to activate these neural structures. We evaluated electromyographic responses evoked in the lower limbs of ten healthy individuals during extension, flexion, and neutral alignment of the thoracolumbar spine. To control for position-specific effects, stimulation in these spine alignment conditions was performed in four different body positions. In comparison to neutral and extended spine alignment, flexion of the spine resulted in a strong reduction of the response amplitudes. There was no such effect on tibial-nerve evoked H reflexes. Further, there was a reduction of post-activation depression of the responses to transcutaneous spinal cord stimulation evoked in spinal flexion. Thus, afferent fibers were reliably activated with neutral and extended spine alignment. Spinal flexion, however, reduced the capacity of the stimulation to activate afferent fibers and led to the co-activation of motor fibers in the anterior roots. This change of action was due to biophysical rather than neurophysiological influences. We recommend applying transcutaneous spinal cord stimulation in body positions that allow individuals to maintain a neutral or extended spine.
Geometric Reproducibility of Three-Dimensional Oral Implant Planning Based on Magnetic Resonance Imaging and Cone-Beam Computed Tomography
Authors: Schwindling Franz , Boehm Sophia , Herpel Christopher , Kronsteiner Dorothea , Vogel Lorenz , Juerchott Alexander , Heiland Sabine , Bendszus Martin , Rammelsberg Peter , Hilgenfeld Tim
Published: December 2021

This study aimed to investigate the geometric reproducibility of three-dimensional (3D) implant planning based on magnetic resonance imaging (MRI) and cone-beam computed tomography (CBCT). Four raters used a backward-planning approach based on CBCT imaging and standard software to position 41 implants in 27 patients. Implant planning was repeated, and the first and second plans were analyzed for geometric differences regarding implant tip, entry-level, and axis. The procedure was then repeated for MRI data of the same patients. Thus, 656 implant plans were available for analysis of intra-rater reproducibility. For both imaging modalities, the second-round 3D implant plans were re-evaluated regarding inter-rater reproducibility. Differences between the modalities were analyzed using paired t-tests. Intra- and inter-rater reproducibility were higher for CBCT than for MRI. Regarding intra-rater deviations, mean values for MRI were 1.7 ± 1.1 mm/1.5 ± 1.1 mm/5.5 ± 4.2° at implant tip/entry-level/axis. For CBCT, corresponding values were 1.3 ± 0.8 mm/1 ± 0.6 mm/4.5 ± 3.1°. Inter-rater comparisons revealed mean values of 2.2 ± 1.3 mm/1.7 ± 1 mm/7.5 ± 4.9° for MRI, and 1.7 ± 1 mm/1.2 ± 0.7 mm/6 ± 3.7° for CBCT. CBCT-based implant planning was more reproducible than MRI. Nevertheless, more research is needed to increase planning reproducibility—for both modalities—thereby standardizing 3D implant planning.
Surgical Aortic Valve Replacement—Age-Dependent Choice of Prosthesis Type
Authors: Vitanova Keti , Wirth Felix , Boehm Johannes , Burri Melchior , Lange Rüdiger , Krane Markus
Published: December 2021

Background: Recently, the use of surgically implanted aortic bioprostheses has been favoured in younger patients. We aimed to analyse the long-term survival and postoperative MACCE (Major Adverse Cardiovascular and Cerebral Event) rates in patients after isolated aortic valve replacement. Methods: We conducted a single-centre observational retrospective study, including all consecutive patients with isolated aortic valve replacement. 1:1 propensity score matching of the preoperative baseline characteristics was performed. Results: A total of 2172 patients were enrolled in the study. After propensity score matching the study included 428 patients: 214 biological vs. 214 mechanical prostheses, divided into two subgroups: group A < 60 years and group B > 60 years. The mean follow-up time was 7.6 ± 3.9 years. Estimated survival was 97 ± 1.9% and 89 ± 3.4% at 10 years for biological and mechanical prosthesis, respectively in group A (p = 0.06). In group B the survival at 10 years was 79.1 ± 5.8% and 69.8 ± 4.4% for biological and mechanical prosthesis, respectively (p = 0.83). In group A, patients with a bioprosthesis exhibited a tendency for higher cumulative incidence MACCE rates compared to patients with a mechanical prosthesis, p = 0.83 (bio 7.3 ± 5.3% vs. mech 4.6 ± 2.2% at 10 years). In group B, patients with a mechanical prosthesis showed a tendency for higher cumulative incidence MACCE rates compared to patients with bioprosthesis, p = 0.86 (bio 4.3 ± 3.1% vs. mech 9.1 ± 3.1% at 10 years). Conclusions: Long-term survival after surgical aortic valve replacement is similar in patients with a biological and mechanical prosthesis, independent of the patients’ age. Moreover, younger patients (<60 years) with bioprosthesis showed a survival benefit, compared to patients with mechanical prosthesis in this age group.
The Problem of Halitosis in Prosthetic Dentistry, and New Approaches to Its Treatment: A Literature Review
Authors: Wyszyńska Magdalena , Nitsze-Wierzba Monika , Białożyt-Bujak Ewa , Kasperski Jacek , Skucha-Nowak Małgorzata
Published: December 2021

The aim of this work is a review of recent scientific literature about intra-oral halitosis among patients using dentures. Halitosis is a condition in which an unpleasant smell comes out of the oral cavity, which is caused mainly by volatile sulfur and non-sulfured compounds. The etiology of halitosis may be intra- or extra-oral; in most patients, however, it is due to the activity of microorganisms in the oral cavity. The problem of the occurrence of intra-oral halitosis has accompanied patients for many years. In dental prosthetics, the problem of halitosis occurs in patients using removable or fixed dentures. In both cases, new niches for the development of microorganisms may be created, including those related to intra-oral halitosis. It should be noted that dentures—both fixed and removable—are a foreign body placed in the patient’s oral cavity which, in case of insufficient hygiene, may constitute a reservoir of microorganisms, causing this unpleasant condition. Conventional treatment of intraoral halitosis reduces microbial activity via chemical and/or mechanical action. Currently, the search for new strategies in the treatment of halitosis is in progress. One idea is to use photodynamic therapy, while another is to modify poly(methyl methacrylate) (PMMA) with silver and graphene nanoparticles. Additionally, attempts have been made to combine those two methods. Another unconventional method of treating halitosis is the use of probiotics.
Achalasia in the Elderly: Diagnostic Approach and a Proposed Treatment Algorithm Based on a Comprehensive Literature Review
Authors: Mari Amir , Sbeit Wisam , Abboud Wisam , Awadie Halim , Khoury Tawfik
Published: December 2021

Achalasia is not uncommonly diagnosed in elderly patients and its incidence and prevalence are growing in this population. However, a scarcity of studies has assessed the typical pathophysiological and clinical features of the disease as well as the effectiveness and safety of the various therapeutic options in elderly populations. Botulinum toxin injection has been used for achalasia treatment since 1994 and is traditionally considered the preferred treatment for fragile elder patients. However, recently more evidence has become available regarding the safety and effectiveness of pneumatic balloon dilation (BD), laparoscopic Heller myotomy (LHM) and per-oral endoscopic myotomy (POEM) in elderly patients with achalasia. In the current review we present the current literature on this topic with a focus on the clinical presentation of achalasia in the elderly and manometric features thereof, as well as summarize the effectiveness and safety of the various therapeutic options. Furthermore, we propose a practical management algorithm as a means to guide the treatment of future cases. We recommend that a conservative/BTI approach should be adopted in the fragile unfit patient. In the elderly fit patient, the treatment decision should be based on the achalasia type, patient preference and the available expertise, similar to the approach adopted for the non-elderly population.
The Impact of COVID-19 Pandemic on Management and Outcome in Patients with Heart Failure
Authors: Abu Ghosh Zahi , Zwas Donna R. , Keren Andre , Elbaz-Greener Gabby , Israeli Vered , Amir Offer , Gotsman Israel
Published: December 2021

Background: The COVID-19 pandemic has adversely affected the provision of health care and disease management around the world. COVID-19 carries a high morbidity and mortality rate in elderly and people with comorbidities, including heart failure (HF). The present study addressed the clinical management and outcomes of HF patients during the pandemic. Methods: We evaluated the clinical management and survival rate of HF patients during the COVID-19 pandemic in Israel (March 2020–April 2021). Results: The cohort included 6748 patients with a diagnosis of HF during the study period. During this period, 843 HF patients (12.5%) were infected with COVID-19, and 194 died from COVID-19, a 23% mortality rate. Patients infected with COVID-19 had a higher percentage of diabetes and obesity. Predictors of mortality included age, male sex, reduced functional capacity, renal dysfunction, and absence of renin–angiotensin system inhibition. During the pandemic, there was a marked decrease in the usage of medical services in the cohort. Cardiovascular hospitalizations, all hospitalization, and emergency room visits were significantly decreased compared to the two years prior to the pandemic, particularly during the lockdowns. There was also an initial decrease in HF clinic visits. Mortality rates were very similar during the pandemic compared to previous years. There was a decline in non-COVID-19 deaths, which were replaced with deaths due to COVID-19. This may result from competing effects and reduced exposure to respiratory infections and other insults due to social distancing. Conclusions: Mortality rates in HF patients infected with COVID-19 were high. The COVID-19 pandemic resulted in the reduced usage of health services but without increased overall mortality.