bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphic Variants of the PDGFRB Gene Influence Efficacy of PRP Therapy in Treating Tennis Elbow: A Prospective Cohort Study
Authors: Szyluk Karol , Jarosz Alicja , Balcerzyk-Matić Anna , Iwanicka Joanna , Iwanicki Tomasz , Nowak Tomasz , Gierek Marcin , Negru Marius , Kalita Marcin , Górczyńska-Kosiorz Sylwia , Kania Wojciech , Niemiec Paweł
Published: October 2022

Background: Differences in response to PRP (platelet-rich plasma) therapy may be linked to the variability of growth factors and their receptor’s genes. Considering that, we checked whether the platelet-derived growth factor receptor beta gene (PDGFRB) single nucleotide polymorphisms (SNPs) affect the effectiveness of PRP therapy in treating tennis elbow patients. Methods: The treatment efficacy was analyzed over time (2, 4, 8, 12, 24, 52, and 104 weeks after PRP injection) on 107 patients (132 elbows) using PROMs (patient-reported outcome measures), namely VAS (Visual Analog Scale), QDASH (quick version of Disabilities of the Arm, Shoulder, and Hand) and PRTEE (Patient-Rated Tennis Elbow Evaluation). Five polymorphisms of the PDGFRB gene (rs4324662, rs758588, rs3828610, rs3756311, and rs3756312) were genotyped. Results: The CC (rs3828610) and GG (rs3756311 and rs3756312) genotypes had a particularly strong impact on the effectiveness of the therapy, as measured by the values of PROMs, both in additive as well as dominant/recessive models. These homozygotes were also characterized by significantly higher values of MPV (mean platelet volume). Conclusions: The PDGFRB gene SNPs affect the effectiveness of PRP therapy in treating tennis elbow patients and it may result from the differentiated metabolic activity of platelets in particular genotype variants.
Risk Factors Associated with Post-Operative Complications in Multidisciplinary Treatment of Descending Necrotizing Mediastinitis
Authors: Congedo Maria Teresa , Nachira Dania , Pennisi Mariano Alberto , Chiappetta Marco , Calabrese Giuseppe , Bello Giuseppe , Parrilla Claudio , Franza Laura , Covino Marcello , Petracca Ciavarella Leonardo , Porziella Venanzio , Vita Maria Letizia , Lococo Filippo , Margaritora Stefano , Meacci Elisa
Published: October 2022

Background: Descending necrotizing mediastinitis (DNM) is a severe, life-threatening complication of oropharyngeal infections with cervical necrotizing fasciitis. In this study, we aimed to identify any possible factors that correlate with favorable outcomes. Methods: We retrospectively analyzed our series of 18 patients who underwent surgical treatment for DNM from a cervical abscess. Gender, age, symptoms, etiopathogenesis, comorbidities, time to surgery from diagnosis, degree of diffusion, identified microorganisms, surgical procedure, days in the intensive care unit, need for tracheostomy, complications, and surgical outcomes were reviewed. Results: The main type of surgery was thoracotomy + cervicotomy in eight cases (50.0%), followed by cervicotomy +VATS in four (22.2%). Seven patients (38.9%) had two or more surgeries; a bilateral operation was necessary for four patients. Evaluating the risk factors associated with post-operative complications, age ≥ 60 years (p:0.031), cervicotomy alone as surgical approach (p = 0.040), and the bilateral approach (p = 0.048) resulted in significance in terms of the univariate analysis; age ≥ 60 years (p = 0.04) and cervical approach (p = 0.05) maintained their significance in terms of the multivariate analysis. Conclusions: The low mortality of our series emphasizes the importance of an extensive and immediate surgical drainage of both the neck and the mediastinum. Mediastinal drainage from cervicotomy seems to be a risk factor for post-operative complications. Minimally invasive surgery on the chest cavity, such as with Uniportal-VATS, could be a good approach above all in elderly patients and all those cases where bilateral access is required.
Ejaculation Sparing Thulium Laser Enucleation of the Prostate: An Observational Prospective Study
Authors: Trama Francesco , Lauro Giovanni Di , Illiano Ester , Iacono Fabrizio , Romis Leo , Mordente Salvatore , Nugnes Maria Rosaria , Lai Stefano , Crocetto Felice , Barone Biagio , Calace Francesco Paolo , Romeo Giuseppe , Costantini Elisabetta
Published: October 2022

Benign prostatic hypertrophy (BPH) is a condition that appears with advancing age and affects 1/3 of men over 50 years, resulting in filling and emptying symptoms. One of the main limitations of endoscopic techniques for BPH is the occurrence of retrograde ejaculation. The purpose of this prospective observational study is to evaluate the efficacy and feasibility of ejaculation-sparing thulium laser enucleation of the prostate (ES-ThuLEP) in the treatment of BPH-related LUTS and the preservation of ejaculation. Sexually active patients with BPH were enrolled and followed up with at 3, 6, and 12 months after surgery. Personal and pharmacological histories were collected, while three standardized questionnaires—the International Index of Erectile Function short form (IIEF-5), the International Consultation on Incontinence Questionnaire for Male Sexual Matters Associated with Lower Urinary Tract Symptoms Module (ICIQ—MLUTSsex), and the International Prostatic Symptom Score (IPSS)—were administered. In addition, all patients underwent uroflowmetry and an assessment of post-void residual volume (PVR). A total of 53 patients were enrolled. A statistically significant improvement in the IPSS score, maximum flow (Qmax), and post-void volume (PVR) at 3 months, 6 months, and 12 months after surgery was found (p < 0.05), while no statistically significant differences were reported between IIEF-5 scores before and after surgery. A total of 48 patients (88.6%) had preserved ejaculation at 3 months, while 92.4% and 94.3% of patients reported preserved ejaculation at 6 and 12 months, respectively. Nevertheless, some degree of hypoposia was referred, at 3, 6, and 12 months, by 43.7%, 30.6%, and 13.2% of patients, respectively. The ES-ThuLEP technique successfully preserved ejaculation in over 90% of patients, representing an ejaculation-sparing alternative in the treatment of BPH.
Serum Leucine-Rich α2 Glycoprotein: A Biomarker for Predicting the Presence of Ulcerative Colitis but Not Ulcerative Proctitis
Authors: Horiuchi Ichitaro , Horiuchi Akira , Umemura Takeji
Published: October 2022

The serum level of leucine-rich α2 glycoprotein (LRG) is a biomarker for active ulcerative colitis (UC). We examined the serum level of LRG as a biomarker for predicting the presence of UC. Patients with persistent diarrhea and/or bloody stool with no history of UC were consecutively enrolled at their initial visit. Serum LRG measurement and colonoscopy with histology were performed on the same day. We enrolled 103 patients (69 men; median age, 45 years) with suspected UC; 66 patients were diagnosed with active UC (proctitis, n = 10; left-sided colitis, n = 26; and pancolitis, n = 30) based on endoscopic and histological criteria. Although the median LRG value in patients with proctitis was similar to that of patients with normal colonoscopic findings (8.5 vs. 8.6 mg/mL, p = 0.24), the median LRG values were significantly elevated in patients with left-sided colitis and pancolitis compared with those of patients with normal colonoscopy (13.6 or 18.0 vs. 8.6 mg/mL, p < 0.0001). The LRG cut-off value of 10.8 μg/mL was derived from the ROC curve, showing 96% sensitivity and 97% specificity for active UC but not active proctitis. Using a cut-off value of 10.8 mg/mL serum, LRG could be a novel biomarker for predicting patients with active UC except for proctitis.
The Gupta Perioperative Risk for Myocardial Infarct or Cardiac Arrest (MICA) Calculator as an Intraoperative Neurologic Deficit Predictor in Carotid Endarterectomy
Authors: Pereira-Macedo Juliana , Lopes-Fernandes Beatriz , Duarte-Gamas Luís , Pereira-Neves António , Mourão Joana , Khairy Ahmed , Andrade José Paulo , Marreiros Ana , Rocha-Neves João
Published: October 2022

Background: Patients undergoing carotid endarterectomy (CEA) may experiment intraoperative neurologic deficits (IND) during carotid cross-clamping. This work aimed to assess the impact of the Gupta Perioperative Myocardial Infarct or Cardiac Arrest (MICA) risk calculator in the IND. Methods: From January 2012 to April 2021, patients undergoing CEA with regional anaesthesia for carotid stenosis with IND and consecutively control operated patients without IND were selected. A regressive predictive model was created, and a receiver operating characteristic (ROC) curve was applied for comparison. A multivariable dependence analysis was conducted using a classification and regression tree (CRT) algorithm. Results: A total of 97 out of 194 included patients developed IND. Obesity showed aOR = 4.01 (95% CI: 1.66–9.67) and MICA score aOR = 1.21 (1.03–1.43). Higher contralateral stenosis showed aOR = 1.29 (1.08–1.53). The AUROC curve was 0.656. The CRT algorithm differentiated obese patients with a MICA score ≥ 8. Regarding non-obese patients, the model identified the presence of contralateral stenosis ≥ 55% with a MICA ≥ 10. Conclusion: MICA score might play an additional role in stratifying patients for IND in CEA. Obesity was determined as the best discrimination factor, followed by a score ≥ 8. A higher ipsilateral stenosis degree is suggested to have a part in avoiding procedure-related IND. Larger studies might validate the benefit of MICA score regarding the risk of IND.
Artificial Intelligence in the Diagnosis of Hepatocellular Carcinoma: A Systematic Review
Authors: Martinino Alessandro , Aloulou Mohammad , Chatterjee Surobhi , Scarano Pereira Juan Pablo , Singhal Saurabh , Patel Tapan , Kirchgesner Thomas Paul-Emile , Agnes Salvatore , Annunziata Salvatore , Treglia Giorgio , Giovinazzo Francesco
Published: October 2022

Hepatocellular carcinoma ranks fifth amongst the most common malignancies and is the third most common cause of cancer-related death globally. Artificial Intelligence is a rapidly growing field of interest. Following the PRISMA reporting guidelines, we conducted a systematic review to retrieve articles reporting the application of AI in HCC detection and characterization. A total of 27 articles were included and analyzed with our composite score for the evaluation of the quality of the publications. The contingency table reported a statistically significant constant improvement over the years of the total quality score (p = 0.004). Different AI methods have been adopted in the included articles correlated with 19 articles studying CT (41.30%), 20 studying US (43.47%), and 7 studying MRI (15.21%). No article has discussed the use of artificial intelligence in PET and X-ray technology. Our systematic approach has shown that previous works in HCC detection and characterization have assessed the comparability of conventional interpretation with machine learning using US, CT, and MRI. The distribution of the imaging techniques in our analysis reflects the usefulness and evolution of medical imaging for the diagnosis of HCC. Moreover, our results highlight an imminent need for data sharing in collaborative data repositories to minimize unnecessary repetition and wastage of resources.
Tailored Direct Oral Anticoagulation in Patients with Atrial Fibrillation: The Future of Oral Anticoagulation?
Authors: Samoš Matej , Bolek Tomáš , Stančiaková Lucia , Péč Martin Jozef , Brisudová Kristína , Škorňová Ingrid , Staško Ján , Mokáň Marián , Kubisz Peter
Published: October 2022

Direct oral anticoagulants (DOAC) are currently the drug of choice for drug prevention of stroke or systemic embolism in patients with atrial fibrillation (AF). However, repeated ischemic stroke or systemic embolism and bleeding while on DOAC is still a challenging clinical phenomenon in the management of future long-term anticoagulation. It is not known whether tailoring the DOAC therapy to achieve optimal therapeutic drug levels could improve the clinical course of DOAC therapy. To be able to tailor the therapy, it is necessary to have a valid laboratory method for DOAC level assessment, to be aware of factors influencing DOAC levels and to have clinical options to tailor the treatment. Furthermore, the data regarding clinical efficacy/safety of tailored DOAC regimes are still lacking. This article reviews the current data on tailored direct oral anticoagulation in patients with AF.
An Observational Prospective Clinical Study for the Evaluation of a Collagen-Hydroxyapatite Composite Scaffold in Hip Revision Surgery
Authors: Cimatti Pietro , Andreoli Isabella , Busacca Maurizio , Govoni Marco , Vivarelli Leonardo , Del Piccolo Nicolandrea , Maso Alessandra , Stagni Cesare , Pignatti Giovanni
Published: October 2022

One of the greatest challenges of hip revision surgery is the need to restore extensive bone loss by creating a stable reconstruction with long-term durability. The present observational, investigator-initiated prospective study was carried out to evaluate the clinical and radiological results of the use of a commercial biomimetic collagen–hydroxyapatite composite biomaterial (RegenOss) applied in hip revision surgery. Thirty-three patients who underwent hip revision were included in this study, and 29 received up to 2 years of follow-up. The acetabulum was reconstructed using an uncemented hemispherical shell both with or without an iliac fixation stem. Functional recovery was assessed according to the Harris Hip Score (HHS) at the pre-hospitalisation check-up, and at 6-, 12-, and 24-month follow-ups. Radiological evaluation consisting of X-ray analyses (6, 12, and 24 month follow-ups) and CT scan exams (within 10 weeks post-surgery and at 12-month follow-up) were performed to evaluate the reduction in bone defect and new bone regeneration. All the patients reported a complete recovery and a considerable improvement in functional outcome assessed by the HHS, which was significantly higher at all the follow-ups than at pre-hospitalisation. Moreover, radiological assessments revealed good scaffold integration. Overall, collected data suggest that RegenOss is a valid and safe alternative to restoring acetabular bone loss in revision hip arthroplasty.
Relationship between Cardiac Acoustic Biomarkers and Pulmonary Artery Pressure in Patients with Heart Failure
Authors: Kaneko Tetsuya , Tanaka Atsushi , Jojima Kota , Yoshida Hisako , Yajima Ayumu , Asaka Machiko , Yamakawa Nobuhide , Kato Tomoyuki , Kotooka Norihiko , Node Koichi
Published: October 2022

Since an elevation of pulmonary artery pressure (PAP) often precedes clinical worsening of heart failure (HF), early and non-invasive detection of this sign is useful in HF care. This study aimed to assess whether cardiac acoustic biomarkers (CABs) are associated with the elevation of PAP in patients with HF. Patients with HF scheduled to undergo right heart catheterization were prospectively enrolled. CABs were concurrently recorded during catheterization at rest (baseline) and while applying a handgrip (exercise). Forty-nine patients were included in the analysis, and their mean PAP significantly increased after exercise compared to baseline. Several CABs correlated significantly with mean PAP by absolute values, among which S2 Width (r = 0.354; p = 0.014 and r = 0.363; p = 0.010) and S3 Strength (r = 0.375; p = 0.009 and r = 0.386; p = 0.007) were consistent throughout baseline and exercise. The response of CABs to exercise-induced PAP elevation was divided into two patterns: increasing and decreasing. The frequency of cardiac index below 2.2 mL/m2 was significantly higher in the decreasing pattern. CABs related to S2 and S3 showed significant correlations with absolute PAP values both at baseline and after exercise in patients with HF, but no significant correlations between their changes from baseline to post-exercise were observed in this study population. Further research is therefore needed to assess whether CABs can sensitively reflect changes in PAP according to HF status and underlying phenotypes.
Trabecular Bone Score as a Reliable Measure of Lumbar Spine Bone Microarchitecture in Acromegalic Patients
Authors: Nazzari Elena , Casabella Andrea , Paolino Sabrina , Campana Claudia , Corica Giuliana , Nista Federica , Milioto Angelo , Tagliafico Alberto , Albertelli Manuela , Boschetti Mara , Bagnasco Marcello , Cutolo Maurizio , Ferone Diego , Gatto Federico
Published: October 2022

Although GH and IGF-1 excess has a controversial impact on bone mineral density (BMD), acromegalic patients display variable degrees of bone structure impairment. In this study, we aim to investigate the usefulness of trabecular bone score (TBS), compared to BMD, in identifying acromegalic patients with impaired lumbar spine trabecular microarchitecture. Forty-four acromegalic patients were investigated for disease control, metabolic and gonadal status, bone metabolism parameters, and the presence of vertebral fractures (VFs). Patients and matched healthy controls underwent BMD and TBS examination. Mean TBS values were lower in patients than in controls (p < 0.001), without significant differences in mean lumbar and femoral BMD. TBS values were significantly higher in controlled patients compared to the uncontrolled ones (p = 0.012). No significant differences were found in bone markers with respect to disease control. Mean TBS or lumbar BMD did not significantly differ in patients with or without VFs (prevalence 11.4%). TBS and BMD levels were lower in hypogonadal patients compared to the eugonadal ones (p = 0.030 and p < 0.001, respectively). In conclusion, TBS values are significantly lower in patients than in controls, confirming the presence of impaired lumbar spine trabecular bone in acromegaly. Both uncontrolled disease and hypogonadism contribute to TBS deterioration in acromegaly.
Serum Levels of Selected IL-1 Family Cytokines in Patients with Morphea
Authors: Szczepanik-Kułak Paulina , Michalska-Jakubus Małgorzata , Kowal Małgorzata , Krasowska Dorota
Published: October 2022

Morphea/localized scleroderma (LoS) represents an inflammatory-sclerotic skin disease, the pathogenesis of which is not fully understood. Given the important role of IL-1 family cytokines in the development and therapy of inflammatory diseases, including systemic sclerosis, we analyzed the clinical significance of serum levels of selected IL-1 family cytokines (IL-1α, IL-1β, IL-18, IL-33, IL-37 and IL-38) in LoS patients (n = 30) using the standardized disease assessment tools and comparison to healthy controls (n = 28). We also compared the pre- and post-treatment concentrations, i.e., before and after systemic (glucocorticosteroids and/or methotrexate) and/or topical (topical glucocorticosteroids and/or calcineurin inhibitors). Our findings did not reveal significant differences in baseline IL-1α, IL-1β, IL-18, IL-33, IL-37 and IL-38 levels between LoS group and HCs; however, after treatment, there were marked changes in concentrations of IL-1α and IL-33 within LoS group as well as in comparison to HCs. We also found significant negative correlations between PGA-A and IL-1α concentration as well as between mLoSSI and IL-1α after treatment. Furthermore, we showed an inverse correlation of baseline IL-1β levels with mLoSSI scores of borderline significance. We believe that IL-1α and IL-33, as well as Il-1β, may be potential mediators and targets of interest in LoS.
Dapsone-Associated Anemia in Heart Transplant Recipients with Normal Glucose-6-Phosphate Dehydrogenase Activity
Authors: Lor Kevin W. , Kransdorf Evan P. , Patel Jignesh K. , Chang David H. , Kobashigawa Jon A. , Kittleson Michelle M.
Published: October 2022

Dapsone is considered an alternative for pneumocystis jirovecii pneumonia (PJP) prophylaxis in sulfa-allergic or -intolerant transplant patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Despite normal G6PD activity, anemia can still occur while on dapsone therapy. We retrospectively reviewed heart transplant patients transplanted at our center between January 2016 and June 2018 and identified those taking dapsone prophylaxis. There were 252 heart transplant recipients at our center between January 2016 and June 2018. 36 patients received dapsone prophylaxis. All had normal G6PD activity assessed prior to dapsone initiation. 8 (22%) patients developed significant anemia attributed to dapsone: 2 were hospitalized for anemia, 1 of whom required blood transfusion. These patients had a median reduction in hemoglobin of 2.1 g/dL from baseline prior to dapsone initiation. Overt evidence of hemolysis was present in six patients. Once dapsone was discontinued, Hgb increased by at least 2 g/dL in a median of 30 days. Anemia from dapsone may occur in a significant proportion of patients despite normal G6PD activity and resulting in significant morbidity. Careful monitoring of transplant recipients on dapsone prophylaxis is warranted, as well as consideration of alternative agents.
Editorial: Apatinib and Anlotinib in the Treatment of Radioactive Iodine Refractory and Highly Invasive Thyroid Carcinoma
Authors: Jia Wenqing , Liu Zhuoran , Zhan Ling , Zhao Qiwu , Qiu Weihua , Kuang Jie
Published: October 2022

Thyroid cancer (TC) is the most prevalent endocrine malignancy, with a rising incidence in the past decade [...]
Mechanical Thrombectomy in Cerebral Venous Sinus Thrombosis: Reports of a Retrospective Single-Center Study
Authors: Jedi Farzaneh , Dethlefs Gero , Hauser Till-Karsten , Hennersdorf Florian , Mengel Annerose , Ernemann Ulrike , Bender Benjamin
Published: October 2022

Current standard care for acute cerebral venous sinus thrombosis (CVST) includes either intravenous heparin or subcutaneous low-molecular-weight heparin, but patients with refractory CVST, despite adequate anticoagulation therapy, may benefit from mechanical thrombectomy (MT). A retrospective study of patients with CVST, who underwent MT between 2011 and 2019, was performed looking at procedure success rate and clinical outcomes. Two raters evaluated the cerebral venous system of every patient before and after the intervention using the following scoring system: (0) No obvious thrombosis; (1) thrombosis without impaired blood flow; (2) thrombosis with impaired blood flow; (3) and thrombosis with complete vascular occlusion. The success of MT was measured using a score quotient (Q = A/B), dividing the sum of the patient’s scores after the intervention (A) by the sum of scores before the intervention (B). Overall, 21 MTs were performed on 20 patients with refractory or severe CVST. Clinical improvement was seen in 61.9% during hospital stay and in 80% at 6-month follow-up, with complete recovery in 70% of patients. Patients with favorable outcomes had significantly lower recanalization quotients (p = 0.008). Our study provides evidence supporting that MT may be a safe and effective treatment with favorable clinical outcomes for selected patients with CVST.
Vitamin-K Antagonists vs. Direct Oral Anticoagulants on Severity of Upper Gastrointestinal Bleeding: A Retrospective Analysis of Italian and UK Data
Authors: Brigida Mattia , Di Caro Simona , Petruzziello Carmine , Saviano Angela , Riccioni Maria Elena , Franceschi Francesco , Ojetti Veronica
Published: October 2022

Background: Gastrointestinal bleeding (GIB) is one of most frequent and significant challenges for emergency physicians and gastroenterologists. Mortality for upper (U) GIB is high, especially in the elderly and comorbid patients. However, there is scant evidence in the literature concerning an assessment of warfarin (VKA) and direct oral anticoagulants (DOACs) in terms of upper gastrointestinal bleeding (UGIB) severity. Aims: Using data from two different settings (Italy and the UK), we aimed to compare the impact of VKA and DOACs on the severity of UGIB. Methods: Retrospective bicentric study on adult patients under VKA or DOACs admitted either to the emergency department at the Gemelli Hospital in Rome, Italy or University College Hospital in London, UK, with suspected UGIB from 01/01/2017 to 31/12/2018. Univariate analysis with Fisher’s exact test, and analysis of variance (ANOVA) were used. Results: 106 patients (62 M/44 F; mean age 71.2 ± 16.9 yrs) were enrolled and divided into the VKA group (N = 57; M: 56%, mean age: 64.9 ± 21.3 yrs) and the DOAC group (N = 49; M: 61%; mean age: 77.6 ± 12.5 yrs). At univariate analysis, the VKA group presented two endoscopic diagnoses more frequently than the DOAC group (26% vs. 8%, p < 0.05), were more frequently endoscopically treated (44% vs. 22%, p < 0.05), rescoped (12% vs. 2%, p = 0.048) and hospitalized (79% vs. 53%, p = 0.01) with a longer length of stay, LOS (VKA: 58% > 5 days vs. DOAC: 68% < 5 days, p = 0.01). There was no difference in terms of hemoglobin level on admission, however the requirement of blood transfusions was higher in the VKA group (60% vs. 41%, p = 0.041). One third of the VKA group showed a lower platelet count than the DOAC group (33% vs. 8%, p = 0.01). No statistically significant differences for in-hospital mortality were observed. For the ANOVA, the type of anticoagulant used was the only significant predictor of need to rescope (p = 0.041) and a significant co-predictor for a LOS > 5 days (p = 0.009; as well as cirrhosis, p = 0.013 and age, p = 0.005). Conclusions: Our outcomes revealed a more severe UGIB in patients on VKA, but the impact of comorbidities (i.e., more cirrhotic patients in the VKA group) cannot be disregarded. DOAC subgroup descriptive analysis, even though on a little cohort, showed higher bleeding severity for rivaroxaban.
Continuous Ropivacaine Peroneal Nerve Infiltration for Fibula Free Flap in Cervicofacial Cancer Surgery: A Randomized Controlled Study
Authors: Motamed Cyrus , Plantevin Frederic , Mazoit Jean Xavier , Julieron Morbize , Bourgain Jean Louis , Billard Valerie
Published: October 2022

Introduction: Pain after cervicofacial cancer surgery with free flap reconstruction is both underestimated and undertreated. There is a rational for regional anesthesia at the flap harvest site, but few studies describe it. We assessed the influence of common peroneal nerve infiltration on pain and opioid consumption in patients having oropharyngeal cancer surgery with fibular free flap mandibular reconstruction. Methods: After institutional review board (IRB) approval and written informed consent, fifty-six patients were randomly allocated to perineural catheter with ropivacaine infiltration (ROPI) or systemic analgesia (CONTROL). In the ROPI group, an epidural catheter was placed by the surgeon before closure, and ropivacaine 0.2% 15 mL, followed by 4 mL/h during 48 h, was administered. The primary outcomes were pain scores and morphine consumption during the 48 h postoperative period. We also measured ropivacaine concentration at the end of infusion. Finally, we retrospectively assessed long-term pain up to 10 years using electronic medical charts. Results: Perineural infiltration of ropivacaine significantly reduced pain scores at the harvest site only at day 1, and did not influence overall postoperative opioid consumption. Ropivacaine assay showed a potentially toxic concentration in 50% of patients. Chronic pain was detected at the harvest site in only one patient (ROPI group), and was located in the cervical area in the case of disease progression. Discussion: Although the catheter was visually positioned by the surgeon, continuous ropivacaine infiltration of the common peroneal nerve did not significantly reduce postoperative pain, but induced a blood concentration close to the toxic threshold at day 2. Further studies considering other infiltration locations or other dosing schemes should be tested in this context, both to improve efficacy and reduce potential toxicity.
Update on Findings about Sudden Sensorineural Hearing Loss and Insight into Its Pathogenesis
Authors: Yamada Satoshi , Kita Junya , Shinmura Daichi , Nakamura Yuki , Sahara Sosuke , Misawa Kiyoshi , Nakanishi Hiroshi
Published: October 2022

Sudden sensorineural hearing loss (SSNHL) is routinely encountered and is one of the most common emergent diseases in otolaryngology clinics. However, the etiology of SSNHL remains unclear. Due to the inaccessibility of the living human inner ear for biopsy, studies investigating the etiology of SSNHL have been performed by analyzing data obtained from examinations using peripheral blood or imaging. We updated the findings obtained from serological, magnetic resonance imaging, genetic, and viral examinations to reveal the etiology of SSNHL. Regarding viral examination, we focused on sensorineural hearing loss associated with coronavirus disease (COVID-19) because the number of correlated reports has been increasing after the outbreak. The updated findings revealed the following three possible mechanisms underlying the development of SSNHL: thrombosis and resulting vascular obstruction in the cochlea, asymptomatic viral infection and resulting damage to the cochlea, and cochlear inflammation and resulting damage to the cochlea. Thrombosis and viral infection are predominant, and cochlear inflammation can be secondarily induced through viral infection or even thrombosis. The findings about sensorineural hearing loss associated with COVID-19 supported the possibility that asymptomatic viral infection is one of the etiologies of SSNHL, and the virus can infect inner ear tissues and directly damage them.
Intraoral Scanners for In Vivo 3D Imaging of the Gingiva and the Alveolar Process
Authors: Winkler Jonas , Sculean Anton , Gkantidis Nikolaos
Published: October 2022

This study aimed to assess the reliability of two intraoral surface scanners for the representation of the alveolar process in vivo. Complete maxillary scans (CS 3600, Carestream and TRIOS 3, 3Shape) were repeatedly obtained from 13 fully dentate individuals. Scanner precision and agreement were tested using 3D surface superimpositions on the following reference areas: the buccal front teeth area, the entire dental arch, the entire alveolar process, or single teeth by applying an iterative closest point algorithm. Following each superimposition, the mean absolute distance (MAD) between predefined 3D model surfaces was calculated. Outcomes were analyzed through non-parametric statistics and the visualization of color-coded distance maps. When superimpositions were performed on the alveolar process, the median scanner precision was below 0.05 mm, with statistically significant but negligible differences between scanners. The agreement between the scanners was approximately 0.06 mm. When single-tooth superimpositions were used to assess the precision of adjacent alveolar soft-tissue surfaces, the median error was 0.028 mm, and there was higher agreement between the scanners. The in vivo reliability of the intraoral scanners in the alveolar surface area was high overall. Single-tooth superimpositions should be preferred for the optimal assessment of neighboring alveolar surface areas relative to the dentition.
Characteristics and Cost of Unscheduled Hospitalizations in Patients Treated with New Oral Anticancer Drugs in Germany: Evidence from the Randomized AMBORA Trial
Authors: Dürr Pauline , Meier Florian , Schlichtig Katja , Schramm Anja , Schötz Lukas , Fromm Martin F. , Dörje Frank
Published: October 2022

Drug-related problems (e.g., adverse drug reactions, ADR) are serious safety issues in patients treated with oral anticancer therapeutics (OAT). The previously published randomized AMBORA trial showed that an intensified clinical pharmacological/pharmaceutical care program within the first 12 weeks of treatment reduces the number and severity of ADR as well as hospitalization rates in 202 patients. The present investigation focused on unscheduled hospitalizations detected within AMBORA and analyzed the characteristics (e.g., frequency, involved OAT) and cost of each hospital stay. To estimate the potential savings of an intensified care program in a larger group, the absolute risk for OAT-related hospitalizations was extrapolated to all insureds of a leading German statutory health insurance company (AOK Bayern). Within 12 weeks, 45 of 202 patients were hospitalized. 50% of all unscheduled hospital admissions were OAT-related (20 of 40) and occurred in 18 patients. The mean cost per inpatient stay was EUR 5873. The intensified AMBORA care program reduced the patients’ absolute risk for OAT-related hospitalization by 11.36%. If this care program would have been implemented in the AOK Bayern collective (3,862,017 insureds) it has the potential to reduce hospitalization rates and thereby cost by a maximum of EUR 4.745 million within 12 weeks after therapy initiation.
New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies
Authors: Sánchez-Tejerina Daniel , Sotoca Javier , Llaurado Arnau , López-Diego Veronica , Juntas-Morales Raul , Salvado Maria
Published: October 2022

Myasthenia gravis (MG) is a chronic autoimmune disease for which multiple immunomodulatory therapies are available. Nevertheless, MG has a significant impact on patient quality of life. In recent years, experts’ main efforts have focused on optimizing treatment strategies, since disease burden is considerably affected by their safety and tolerability profiles, especially in patients with refractory phenotypes. This article aims to offer neurologists caring for MG patients an overview of the most innovative targeted drugs specifically designed for this disease and summarizes the recent literature and more recent evidence on agents targeting B cells and plasmablasts, complement inhibitors, and neonatal fragment crystallizable receptor (FcRn) antagonists. Positive clinical trial results have been reported, and other studies are ongoing. Finally, we briefly discuss how the introduction of these novel targeted immunological therapies in a changing management paradigm would affect not only clinical outcomes, disease burden, safety, and tolerability, but also health spending in a condition that is increasingly managed based on a patient-centred model.
Pregnancy Outcomes after Frozen Embryo Transfer and Fresh Embryo Transfer in Women of Advanced Maternal Age: Single-Center Experience
Authors: Chen Yao , Zhou Jianbo , Chen Yandong , Yang Jihong , Hao Yingying , Feng Ting , Feng Ruizhi , Qian Yun
Published: October 2022

Delayed childbearing leads to increased assisted reproductive technology use by women of advanced maternal age (AMA). It is unclear whether fresh or frozen embryo transfer (FET) is the better option. We aimed to assess maternal and neonatal outcomes in patients having their first FET after a freeze-all cycle versus those having their first fresh embryo transfer (ET). We reviewed 720 women of AMA undergoing a first fresh ET (n = 375) or FET (n = 345) between January 2016 and April 2021. No significant difference in the live birth rate was found between FET and fresh ET (19.7% vs. 24.3%, p = 0.141). The clinical pregnancy rate was significantly lower in the FET group than in the fresh ET group (26.4 % (91/345) vs. 33.6% (126/375), p = 0.035), but FET resulted in higher birthweights (3217.16 ± 734.44 vs. 3003.37 ± 635.00, p = 0.037) and was associated with a lower incidence of preterm births (2.6% vs. 5.6%, p = 0.046). The risks of other maternal and neonatal outcomes did not differ significantly between the groups. Among women of AMA, the transfer of frozen embryos did not result in significantly higher rates of live birth than fresh embryos did; however, a freeze-all strategy may not be beneficial for the women of AMA.
Relationship between Oral Parafunctional and Postural Habits and the Symptoms of Temporomandibular Disorders: A Survey-Based Cross-Sectional Cohort Study Using Propensity Score Matching Analysis
Authors: Abe Susumu , Kawano Fumiaki , Matsuka Yoshizo , Masuda Taeko , Okawa Toshinori , Tanaka Eiji
Published: October 2022

Temporomandibular disorders (TMDs) are a multifactorial joint disease of the masticatory system. The possible etiological factors involved in the onset and progression of TMDs include oral parafunctional habits (OPFHs) and postural habits (PHs). However, little information is available on the association between OPFHs and PHs and a predisposition to TMDs. Thus, to investigate whether the presence of OPFH and PH predisposes individuals to TMDs, a survey-based cross-sectional cohort study of self-reported TMD was performed. A total of 2292 patients with TMD were recruited for the survey. Through one-to-one propensity score matching, 166 patients with and without sleep bruxism (SB) were selected. The SB group had a significantly higher risk of masticatory muscular pain or fatigue than the non-SB group (p = 0.018). Furthermore, the SB group without other OFPHs and PHs did not show a significantly higher risk of TMD symptoms than the non-SB group. Diurnal clenching and bad posture also affect the stomatognathic system, causing pain or fatigue; however, it did not result in TMDs in patients without any OPFHs and PHs. This implies that OPFHs and PHs may increase the risk of TMD symptoms in coexistence with other habits.
Prospective Comparison of Local Anesthesia with General or Spinal Anesthesia in Patients Treated with Microscopic Varicocelectomy
Authors: Wang Xiaobin , Pan Chunyu , Li Jia , Zhan Yunhong , Liu Gang , Bai Song , Chai Jun , Shan Liping
Published: October 2022

It is unclear whether local anesthesia (LA) is a viable and safe alternative to general anesthesia (GA) or spinal anesthesia (SA) for microscopic varicocelectomy. As a result, we designed a prospective trial to compare the pain relief, complications, and cost of LA with GA or SA in subinguinal microscopic varicocelectomy (MSV), using the propensity score matching method (PSM). This prospective study was conducted in a tertiary hospital from February 2021 to April 2022. Patients who underwent subinguinal MSV for varicocele were enrolled. The perioperative visual analog scale (VAS) scores, anesthesia-associated side effects, and cost data were recorded, and PSM analysis was performed. Finally, 354 patients were included, of whom 61.0% (216) were treated with LA, and 39.0% (138) underwent GA or LA. After PSM, the patients in the LA group exhibited lower VAS scores both three hours and one day after surgery, and a lower incidence of postoperative analgesic requirement; a lower ratio of patients who experienced anesthesia-associated side effects was also observed in the LA group, compared with the GA or SA group (all p < 0.001). The rate of perioperative satisfaction for patients was higher, the hospital stays and days to return to normal activity were shorter, and the cost was less in the LA group than in the patients in the GA or SA group (all p < 0.001). This prospective PSM cohort demonstrated that LA has the advantages of perioperative pain relief, reduced anesthesia-associated side effects, and cost, compared with GA or SA. It indicated that LA is an effective and safe technique for subinguinal MSV, and may guide clinical practice.
A Four-Stepwise Electrocardiographic Algorithm for Differentiation of Ventricular Arrhythmias Originated from Left Ventricular Outflow Tract
Authors: Tan Hong-Wei , Gao Wei-Dong , Wang Xin-Hua , Chen Zhi-Song , Liu Xue-Bo
Published: October 2022

Several electrocardiographic algorithms have been proposed to identify the site of origin for the ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) versus right ventricular outflow tract. However, the electrocardiographic criteria for distinguishing VAs originated from the different sites of LVOT is lacking. We aimed to develop a simple and efficient ECG algorithm to differentiate LVOT VAs originated from the aortic root, AMC and LV summit. We analyzed 12-lead ECG characteristics of 68 consecutive patients who underwent successful radiofrequency catheter ablation of symptomatic VAs from LVOT. Patients were divided into RCC (right coronary cusp) group (n = 8), the L-RCC (the junction between the LCC and RCC) group (n = 21), the LCC (left coronary cusp) group (n = 24), the aortomitral continuity (AMC) group (n = 9) and the LV summit group (n = 6) according to the final ablation sites. Measurements with the highest diagnostic performance were modeled into a 4-stepwise algorithm to discriminate LVOT VAs. The performance of this novel algorithm was prospectively tested in a validation cohort of 43 consecutive patients undergoing LVOT VAs ablation. Based on the accuracy of AUC, a 4-stepwise ECG algorithm was developed. First, the QS duration in aVL > 134 ms was used to distinguish VAs from AMC, LV summit and VAs from aortic root (80% sensitivity and 76% specificity). Second, the R duration in II > 155 ms was used to differentiate VAs from LV summit and VAs from AMC (67% sensitivity and 56% specificity). Third, the ratio of III/II < 0.9 was used to discriminate VAs from RCC and VAs from LCC, L-RCC (82% sensitivity and 63% specificity). Fourth, the QS duration of aVR > 130 ms was used to discern VAs from LCC and VAs from L-RCC (75% sensitivity and 62% specificity). In the prospective evaluation, our 4-stepwise ECG algorithm exhibited a good predictive value. We have developed a novel and simple 4-stepwise ECG algorithm with good predictive value to discriminate the AVs from different sites of LVOT.
Plasma-Methylated SEPT9 for the Noninvasive Diagnosis of Gastric Cancer
Authors: Zhao Luyao , Li Muran , Zhang Shiwu , Liu Yandi
Published: October 2022

Background. Gastric cancer (GC) is one of the most prevalent cancers globally. This study was designed to evaluate the potential performance of plasma SEPT9 methylation (mSEPT9) as a noninvasive biomarker for the diagnosis of GC. Methods. A total of 182 participants, i.e., 60 patients with GC, 39 with chronic superficial gastritis (CSG), 27 with chronic atrophic gastritis (CAG), 30 with gastric ulcer (GU), and 26 with gastric polys (GP), were recruited. The mSEPT9 level was measured using real-time polymerase chain reaction. Results. As a diagnostic target, mSEPT9 (1/3 algorithm) had a sensitivity of 48.33 (95% confidence interval (CI): 35.40–61.48%) and a specificity of 86.89% (95% CI: 79.28–92.09%), and mSEPT9 (2/3 algorithm) had a sensitivity of 33.33 (95% CI: 22.02–46.79%) and a specificity of 98.36% (95% CI: 93.61–99.72%). The area under the receiver operating characteristic curve (ROC) curve of mSEPT9 was 0.698 (95% CI: 0.609–0.787) for the differentiation of GC from benign gastric diseases. The effectiveness of mSEPT9 (1/3 algorithm) was superior to that of CEA, CA19-9, and CA72-4. mSEPT9 was positively correlated with T, N, M, and the clinical stage of GC. Conclusions. Plasma mSEPT9 might serve as a useful and noninvasive biomarker for the diagnosis of GC.
The First Evidence on the Occurrence of Bisphenol Analogues in the Aqueous Humor of Patients Undergoing Cataract Surgery
Authors: Flieger Jolanta , Śniegocki Tomasz , Dolar-Szczasny Joanna , Załuska Wojciech , Rejdak Robert
Published: October 2022

Human exposure to BPs is inevitable mostly due to contaminated food. In this preliminary study, for the first time, the presence of bisphenols (BPs) in aqueous humor (AH) collected from 44 patients undergoing cataract surgery was investigated. The measurements were performed using a sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS). Chromatographic separation was achieved using a reverse-phase column and a gradient elution mode. Multiple reaction monitoring (MRM) was used. The method was validated for bisphenol A (BPA) and bisphenol F (BPF). The limits of quantification (LOQs) of both investigated analytes were 0.25 ng mL−1. The method was linear in the range of 0.25–20.0 ng mL−1 with correlation coefficients (R2) higher than 0.98. Recovery of analytes was in the range of 99.9 to 104.3% and intra-assay and inter-assay precision expressed by relative standard deviations (RSD%) were less than 5%. BPA was detected in 12 AH samples with mean concentrations of 1.41 ng mL−1. BPF was not detected at all. Furthermore, two structural isomers termed BPA-1, and BPA-2 were identified, for the first time, in 40.9% of the AH samples, with almost twice higher mean concentrations of 2.15 ng mL−1, and 2.25 ng mL−1, respectively. The total content of BPs were higher in patients with coexisting ocular pathologies such as glaucoma, age-related macular degeneration (AMD), and diabetes in comparison to cataracts alone. However, the difference between these groups did not reach statistical significance (p > 0.05). Performed investigations indicate the need for further research on a larger population with the aim of knowing the consequences of BPs’ accumulation in AH for visual function.
Electroretinographic Assessments of Macular Function after Brilliant Blue G Staining for Inner Limiting Membrane Peeling
Authors: Terauchi Gaku , Shinoda Kei , Yagura Kazuma , Kawashima Makoto , Matsumoto Soiti Celso , Mizota Atsushi , Miyake Yozo
Published: October 2022

Purpose: The purpose of this study was to determine the effect of brilliant blue G (BBG) staining of the inner limiting membrane (ILM) on macular function. Method: Fourteen eyes of 14 patients consisting of 9 men and 5 women who underwent vitreous surgery with ILM peeling were studied. The mean age of the patients was 68.8 ± 9.14 years. Three eyes had a macular hole and eleven eyes had an epiretinal membrane. The ILM was made more visible by spraying 0.25% BBG into the vitreous cavity. The macular function was assessed by recording intraoperative focal macular electroretinograms (iFMERGs) before and after the intravitreal spraying of the BBG dye. The iFMERGs were recorded three times after core vitrectomy. The first recording was performed before the BBG injection (Phase 1, baseline), the second recording was performed after the spraying of the BBG and washing out the excess BBG (Phase 2), and the third recording was performed after the ILM peeling (Phase 3). All recordings were performed after 5 min of light-adaptation and stabilization of the intraocular conditions. The iFMERGs were recorded twice at each phase. The implicit times and amplitudes of the a- and b-wave, the PhNR, and the d-wave were measured. Wilcoxon signed-rank test were used to determine the significance of differences of the findings at Phase 2 vs. Phase 1 and Phase 3 vs. Phase 1. A p value < 0.05 was taken to be statistically significant. Results: The average implicit times of the a-wave, b-wave, PhNR, and d-wave were not significantly different in Phase 1, 2, and 3. The average a-wave, b-wave, PhNR, and d-wave amplitudes at Phase 1 did not differ significantly from that at Phase 2 and at Phase 3. Conclusions: The results indicated that the intravitreal injection of BBG does not alter the physiology of the macula, and we conclude that BBG is safe. We also conclude that iFMERGs can be used to monitor the macular function safely during intraocular surgery.