bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Generalized Displacement Boundary and Its Analytical Prediction for Ground Movements Induced by Shield Tunneling
Authors: Tang Qianlong , Chen Fudong , Lei Mingfeng , Zhu Binbin , Peng Limin
Published: March 2021

The process of shield tunnel excavation would inevitably cause surrounding ground movement, and excessive displacement in the soil could lead to large deformation and even collapse of the tunnel. The methods estimating convergence deformation around tunnel opening is summarized. Then, a universal pattern of displacement boundary condition around the tunnel cavity is originally introduced, which is solved as the combination of three fundamental deformation modes, namely, uniform convergence, vertical translation, and ovalization. The expression for the above‐mentioned displacement boundary condition is derived, by imposing which the analytical solution for ground movements, based on the stress function method, is proposed. The reliability and applicability of this proposed solution are verified by comparing the observed data in terms of surface settlement, underground settlement, and horizontal displacement. Further parametric analyses indicate the following: (1) the maximum settlement increases linearly with the gap parameter and the tunnel radius, while it is negatively related to the tunnel depth; (2) the trough width parameter is independent of the gap parameter and the radius, while it is proportional to the tunnel depth. This study provides a new simple and reliable method for predicting ground movements induced by shield tunneling.
A Bracket‐Stiffened Two‐Planar Overlapped Tubular KT‐Joint for Offshore Jack‐Up Fatigue Analysis
Authors: Zhang Jian , Yue Xinxin , Qiu Jiajia , Chen Lei , Shen Wei
Published: March 2021

There have been a large number of research programs dedicated to the investigation of stress concentration factor and its parametric design formulae for a variety of uniplanar and multiplanar tubular joints. However, for the multiplanar overlapped tubular joints, the related reports are very limited due to the fact that the combining effect between multiplanarity and brace overlapping is quite complex. In this paper, a novel bracket‐stiffened two‐planar overlapped tubular KT‐joint is proposed by adding two brackets between the upper diagonal and horizontal braces to alleviate the stress concentration at the brace‐to‐chord intersection area. As compared with the original KT‐joint and KT‐joint of larger brace gap, stress concentration reduction and fatigue strength enhancement at the most critical point of the proposed KT‐joint are significant under both axial and in‐plane bending (IPB) loads. The superiority of the proposed KT‐joint is further tested with a simplified fatigue life assessment of offshore jack‐up in field transit condition, when the KT‐joint corresponding to the upper guide level is most critical and fatigue‐sensitive. The obtained results with conservative assumptions may serve as guides or references in civil and offshore engineering practices.
Health Behavior and Lifestyle Trends among Platelet Donors: Results from a Questionnaire‐Based Survey in Norway
Authors: Mousavi Seyed Ali , Hermundstad Brita , Saether Per Christian , Nybruket Monica Jenssen , Knutsen Teresa Risopatron , Llohn Abid Hussain
Published: March 2021

Background. Blood donors are on average healthier than the general population, a phenomenon known as the “healthy donor effect.” Earlier studies have also pointed to healthier behaviors among whole blood donors than the general population. This study is aimed at assessing the prevalence of four healthy behaviors (sufficient physical activity, avoiding cigarette smoking, low to moderate alcohol use, and maintaining a healthy weight) among platelet donors and to compare the results with those in the general population of similar ages. Methods. Eighty‐six platelet donors were asked to complete a questionnaire designed to assess physical activity, smoking, and alcohol use. Sociodemographic information including gender, age, and education was also collected from all participants. Chi‐square statistics and logistic regression were used in statistical analysis. Results. The mean age of the study donors was 51 years, 56% were female. Most were employed (90%), and 48% hold a bachelor’s or higher degree. The prevalence of healthy behaviors differed by education gradients but not by gender and age. About 49% of the donors met the weekly physical activity recommendations, less than 5% were daily smokers, and~26% were classified as more frequent drinkers (≥1 to ≤5 times per week). The corresponding percentages for the general population were, respectively, 33%, 13%, and 35%. The prevalence of overweight and obesity, as assessed by body mass index (BMI), among donors were 50% and 29%, respectively, much higher than the current prevalence of overweight and obesity of 37% and 19%, respectively, among adults in the general population. Conclusions. The individual health behaviors of the majority of the study population could be characterized by a relatively high level of physical activity, low prevalence of daily smoking, and moderate alcohol drinking. The above‐average overweight/obesity prevalence among platelet donors in this cohort is of concern because of the potential serious health consequences and it warrants further reflection.
Obesity-Dependent Adipokine Chemerin Suppresses Fatty Acid Oxidation to Confer Ferroptosis Resistance
Authors: Tan Sze Kiat , Mahmud Iqbal , Fontanesi Flavia , Puchowicz Michelle , Neumann Chase K.A. , Griswold Anthony J. , Patel Rutulkumar , Dispagna Marco , Ahmed Hamzah H. , Gonzalgo Mark L. , Brown J. Mark , Garrett Timothy J. , Welford Scott M.
Published: March 2021

Clear cell renal cell carcinoma (ccRCC) is characterized by accumulation of neutral lipids and adipogenic transdifferentiation. We assessed adipokine expression in ccRCC and found that tumor tissues and patient plasma exhibit obesity-dependent elevations of the adipokine chemerin. Attenuation of chemerin by several approaches led to significant reduction in lipid deposition and impairment of tumor cell growth in vitro and in vivo. A multi-omics approach revealed that chemerin suppresses fatty acid oxidation, preventing ferroptosis, and maintains fatty acid levels that activate hypoxia-inducible factor 2α expression. The lipid coenzyme Q and mitochondrial complex IV, whose biogeneses are lipid-dependent, were found to be decreased after chemerin inhibition, contributing to lipid reactive oxygen species production. Monoclonal antibody targeting chemerin led to reduced lipid storage and diminished tumor growth, demonstrating translational potential of chemerin inhibition. Collectively, the results suggest that obesity and tumor cells contribute to ccRCC through the expression of chemerin, which is indispensable in ccRCC biology.

Significance:

Identification of a hypoxia-inducible factor–dependent adipokine that prevents fatty acid oxidation and causes escape from ferroptosis highlights a critical metabolic dependency unique in the clear cell subtype of kidney cancer. Targeting lipid metabolism via inhibition of a soluble factor is a promising pharmacologic approach to expand therapeutic strategies for patients with ccRCC.

See related commentary by Reznik et al., p. 1879.

This article is highlighted in the In This Issue feature, p. 1861
Clinicopathological Features, Prognostic Factors, Survival Trends, and Treatment of Malignant Ovarian Germ Cell Tumors: A SEER Database Analysis
Authors: Guo Hualei , Chen Hao , Wang Wenhui , Chen Lingna
Published: March 2021

Objective: The aim of this study was to investigate the clinicopathological prognostic factors of malignant ovarian germ cell tumors (MOGCT) and evaluate the survival trends of MOGCT by histotype. Methods: We extracted data on 1,963 MOGCT cases diagnosed between 2000 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database and the histological classification of MOGCT, including 5 categories: dysgerminoma, embryonal carcinoma (EC), yolk sac tumor, malignant teratoma, and mixed germ cell tumor. We examined overall and disease-specific survival of the 5 histological types. Kaplan-Meier and Cox proportional hazards regression models were used to estimate survival curves and prognostic factors. We also estimated survival curves of MOGCT according to different treatments. Results: There was a significant difference in prognosis among different histological classifications. Age, histotype, grade, SEER stage, and surgery were independent prognostic factors for survival of patients with MOGCT. For all histotypes, 1-, 3-, and 5-year survival rate estimates were >85%, except for EC, which had the worst outcomes at 1 year (55.6%), 3 years (44.4%), and 5 years (33.3%). In the distant SEER stage, both chemotherapy and surgery were associated with improved survival outcomes compared with surgery- and chemotherapy-only groups. Conclusions: Dysgerminoma patients had the most favorable outcomes, whereas EC patients had the worst survival. A young age, low grade, and surgery were all significant predictors for improved survival. In contrast, a distant SEER stage was a risk factor for poor survival. Chemotherapy combined with surgery contributed to longer survival times of patients with MOGCT in the distant SEER stage.
Atrophy in Distinct Corticolimbic Networks Subserving Socioaffective Behavior in Semantic Variant Primary Progressive Aphasia
Authors: Eldaief Mark C. , Perez David L. , Quimby Megan , Hochberg Daisy , Touroutoglou Alexandra , Feldman Barrett Lisa , Dickerson Bradford C.
Published: March 2021

Background: Although traditionally conceptualized as a language disorder, semantic variant primary progressive aphasia (svPPA) is often accompanied by significant behavioral and affective symptoms which considerably increase disease morbidity. Specifically, these neuropsychiatric symptoms are characterized by breaches in normative socioaffective function, for example, an inability to read social cues, excessive trusting of others, and decreased empathy. Our prior neuroimaging work identified 3 corticolimbic networks anchored in the amygdala, temporal pole, and frontoinsular cortex: an affiliation network, theorized to mediate social approach behavior; an aversion network, theorized to subserve the appraisal of social threat; and a perception network, theorized to mediate the detection of social cues. We hy­pothesized that degeneration of these networks could provide neuroanatomical substrates for socioaffective deficits in svPPA. Methods: We examined hypothesized relationships between subscores on the Social Impairment Rating Scale (SIRS) and atrophy in each of these 3 networks in a group of 16 svPPA patients (using matched cognitively normal controls as a reference). Results: Consistent with our predictions, the magnitude of atrophy in the affiliation network in svPPA patients correlated with the SIRS subscore of socioemotional detachment, while the magnitude of atrophy in the aversion network in svPPA patients correlated with the SIRS subscore of inappropriate trusting. We did not find the predicted association between perception network atrophy and the SIRS subscore of lack of attention to social cues. Conclusion: These findings highlight specific socioaffective deficits in svPPA and provide a neuroanatomical basis for these impairments by linking them to networks commonly targeted in this disorder.
Mistletoe Extract Viscum Fraxini-2 for Treatment of Advanced Hepatocellular Carcinoma: A Case Series
Authors: Lee Richard T. , Yang Peiying , Alahmadi Asrar , McQuade Jennifer , Yuan Eric , Difeo Analisa , Narla Goutham , Kaseb Ahmed
Published: March 2021

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of death from cancer worldwide, and for advanced HCC the prognosis is poor. Preliminary studies indicate mistletoe extracts may have anticancer activity for HCC. Methods: A prospective observational case series of advanced HCC patients that chose to take a mistletoe extract called viscum fraxini-2 (VF-2) alone for treatment. Time on treatment, imaging, and laboratory values were collected for descriptive analyses. Results: A total of 12 patients with advanced HCC enrolled onto the protocol, and 10 patients had data available for evaluation. The majority were male (10/12) with a median age of 64 (SD 11). Most patients had received sorafenib therapy (9/12) and had varying Child-Pugh classes (A-4, B-6, C-2). Treatment with VF-2 ranged from 1 to 36 weeks with a mean of 12.3 weeks (SD 12). Six patients received 8 weeks of treatment, and 3 patients received 12 or more weeks of treatment. For patients that received at least 4 weeks of treatment, the average AFP value stabilized during the first 4 weeks of treatment. Two patients experienced an AFP decrease of >30%, approximately 37 and 40% decreases at the nadir. One patient had stable disease of 9 months. Major side effects were fever, fatigue, rash, and local injection site reaction of swelling, redness, and tenderness. Conclusion: This case series of advanced HCC indicates that mistletoe extract VF-2 may have potential biological activity against HCC for selected patients. Research is needed to identify the active compound and predictive markers of response.
CT Findings of Primary Renal Angiosarcoma
Authors: Komoto Hisashi , Kitajima Kazuhiro , Kawanaka Yusuke , Yoshimura Nahomi , Kunimoto Ryo , Yokoyama Hiroyuki , Shinkai Yukako , Kaizuka Yohei , Yamamoto Shingo , Kihara Takako , Kimura Neinei , Hirota Seiichi , Yamakado Koichiro
Published: March 2021

Primary angiosarcomas of the kidney are very rare but highly aggressive tumors showing poor prognosis. We present a case of primary renal angiosarcoma occurring in a 60-year-old man with left flank pain. CT images depicted a huge exophytic mass (14 cm in diameter) in the left kidney, exhibiting central extensive hemorrhage or necrosis without contrast enhancement. The mass showed centripetal peripheral nodular enhancement on dynamic contrast-enhanced CT images. We suggest its inclusion in the differential diagnosis of cases of hemorrhagic renal tumors with prominent vasculature.
Transformation of Acute Myeloid Leukemia with Deletion of Chromosome 7q and Additional Abnormalities in Chromosome 8 in a Patient with Essential Thrombocythemia
Authors: Shimizu Ayaka , Takenaka Kei , Ohata Shinya , Morimoto Kazuhide , Hashimoto Hiromi , Yamamoto Yuki , Itoh Toshio , Sugimoto Takeshi
Published: March 2021

This is a case report of a 60-year-old male patient with essential thrombocythemia (ET) that progressed to acute myeloid leukemia (AML) in approximately 9 years. His platelet count decreased approximately 8 years after ET treatment with hydroxyurea (HU) and aspirin. The dose of HU was reduced because of suspected myelosuppression due to HU; however, myelosuppression did not improve. Bone marrow examination revealed myelofibrosis; therefore, ruxolitinib was administered. Approximately 1 year later, his leukocyte and blast counts in the peripheral blood increased; thus, ET was judged to have progressed to AML-myelodysplasia-related change. Induction chemotherapy and consolidation therapy were initiated; however, the patient unfortunately failed to achieve complete remission. We then continued to administer salvage chemotherapy; however, his general condition worsened, and he died from cerebral hemorrhage. The karyotype at the onset of ET was 46,XY, which changed to 47,XY,del(7q),+8 at the time of AML diagnosis. In addition, genetic testing revealed FLT-3 ITD mutation. His histopathological analysis showed subarachnoid and intraparenchymal hemorrhages and tumor cell infiltration into the cerebrum, brainstem, and cerebellum. In this case, deletion of the long arm of chromosome 7, additional abnormalities in chromosome 8, and FLT3-ITD mutation were confirmed as risk factors for having developed secondary AML for approximately 9 years and death from cerebral hemorrhage 1 year later.
Horizontal Gaze Defect as a Result of Subcortical Stroke: Case Report and Review of the Literature
Authors: Alshahrani Abdulrahman M.
Published: March 2021

Gaze palsies are commonly observed in the setting of acute stroke; such strokes are nearly always localized to either cerebral cortical or brainstem areas. Much less common are lesions localized at the subcortical pathways involved in the control of eye movements. We report a patient with subcortical white matter ischemic stroke who suffered horizontal gaze defects.
Prenatal Imaging Diagnosis of Suprarenal Lesions
Authors: Lazow Stefanie P. , Richman Danielle M. , Dionigi Beatrice , Staffa Steven J. , Benson Carol B. , Buchmiller Terry L.
Published: March 2021

Introduction: Prenatal suprarenal lesions represent diverse pathologies. This study investigated prenatal imaging features and regression patterns associated with specific lesion diagnoses. Methods: This is a multicenter retrospective review of fetuses with prenatally diagnosed suprarenal lesions between 2001 and 2019. Prenatal ultrasound and MRI characteristics, postnatal imaging, and clinical course were reviewed. Prenatal imaging findings were compared by the most common diagnoses and regression patterns. Results: Forty-four fetuses were prenatally diagnosed with suprarenal lesions. Diagnoses included pulmonary sequestration (n = 12; 27.3%), adrenal hemorrhage (n = 12; 27.3%), upper quadrant cyst (including 2 duplication cysts, 1 splenic cyst, and 3 indeterminate cysts), neuroblastoma (n = 4), adrenal hyperplasia (n = 3), bilateral adrenal calcifications (n = 1), and indeterminate lesions (n = 6). Sequestrations were uniformly left-sided (100 vs. 50%; p = 0.014) and diagnosed earlier in gestation than adrenal hemorrhages (p = 0.025). Sequestrations were also significantly more likely to have a prenatal feeding vessel (p = 0.005), low T1 MRI signal (p = 0.015), and no MRI blood products (p = 0.018) compared to adrenal hemorrhages. When comparing all 44 patients, a prenatal feeding vessel and low T1 signal on prenatal MRI were significantly associated with lesion persistence (p = 0.003; p = 0.044). Discussion/Conclusion: Imaging findings on prenatal ultrasound and MRI aid in the diagnosis of suprarenal lesions, including differentiating pulmonary sequestrations and adrenal hemorrhages.
Detection of Microsatellite Instability via Circulating Tumor DNA and Response to Immunotherapy in Metastatic Castration-Resistant Prostate Cancer: A Case Series
Authors: Ravindranathan Deepak , Russler Greta Anne , Yantorni Lauren , Drusbosky Leylah M. , Bilen Mehmet Asim
Published: March 2021

Pembrolizumab has been approved by the US Food and Drug Administration for the treatment of metastatic or unresectable solid tumors that are microsatellite instability-high (MSI-H) or mismatch repair deficient. Blood-based circulating tumor DNA (ctDNA) assays have been validated to identify tumors with MSI-H status without the need for tissue biopsy. We report 2 patients with metastatic castration-resistant prostate cancer (mCRPC) who had prior treatment with multiple lines of therapy and underwent ctDNA testing, which detected MSI-H status. Both patients were treated with pembrolizumab, resulting in an excellent clinical response measured with liquid biopsies before and after initiation of therapy, which demonstrated a significant reduction in somatic-variant allele frequency in addition to a decrease in prostate serum antigen levels.
A Low-Grade Trichoblastic Carcinoma Treated with Mohs Micrographic Surgery
Authors: Leeman Annemiek , de Cuba Erienne M.V. , Jaspars Lies H. , Quint Koen D. , Genders Roel E.
Published: March 2021

Trichoblastomas are rare dermal neoplasms usually found on the scalp and face. Histology shows a proliferation of small basaloid cells arranged in cords or fields surrounded by cellular stroma. Trichoblastomas are usually not aggressive, but trichoblastic carcinomas arising from preexisting trichoblastomas have been described and have been linked to basal cell carcinoma. We found a tumor with features of trichoblastoma with presence of Merkel cells, but with a deeply infiltrative growth pattern into the fat and muscle tissue, without significant architectural or cellular atypia. Tumors with similar growth patterns were previously described as deeply invasive trichoblastic neoplasms. It appears to be a new entity that has been described before but has not been fully characterized: low-grade trichoblastic carcinoma. This malignancy seems to show only locally aggressive growth. Radical excision was accomplished with Mohs micrographic surgery.
Prenatal Imaging Features and Postnatal Outcome of Short Corpus Callosum: A Series of 42 Cases
Authors: Bartholmot Caroline , Cabet Sara , Massoud Mona , Massardier Jérôme , Fichez Axel , Des Portes Vincent , Guibaud Laurent
Published: March 2021

Objectives: Our goal was to provide a better understanding of isolated short corpus callosum (SCC) regarding prenatal diagnosis and postnatal outcome. Methods: We retrospectively reviewed prenatal and postnatal imaging, clinical, and biological data from 42 cases with isolated SCC. Results: Prenatal imaging showed SCC in all cases (n = 42). SCC was limited to rostrum and/or genu and/or splenium in 21 cases, involved body in 16 cases, and was more extensive in 5 cases. Indirect imaging features included typical buffalo horn ventricles (n = 14), septal dysmorphism (n = 14), parallel lateral ventricles (n = 12), and ventriculomegaly (n = 4), as well as atypical features in 5 cases. SCC was associated with interhemispheric cysts and pericallosal lipomas in 3 and 6 cases, respectively. Aneuploidy was found in 2 cases. Normal psychomotor development, mild developmental disorders, and global developmental delay were found in 70, 15, and 15% of our cases, respectively. Conclusions: SCC should be investigated to look for pericallosal lipoma and typical versus atypical indirect features of corpus callosum agenesis (CCA). Prenatal counselling should be guided by imaging as well as clinical and genetic context. Outcome of patients with SCC was similar to the one presenting with complete CCA.
Synchronous Melanoma and Pancreas Malignancies Leading to a Discovery of a CDKN2A Mutation in a Patient with No Known Family History
Authors: O’Reilly Mary , Keane Fergus , Mc Dermott Ray
Published: March 2021

We report a case of a 60-year-old male with metachronous primary malignancies, pancreatic cancer and malignant melanoma which recurred simultaneously. Both cancers were challenging to diagnose and throughout the case at different times, the presence of two active malignancies obscured the clinical picture. A bleeding gastric lesion found in the stomach 6 months after a distal pancreatectomy for pancreatic adenocarcinoma revealed metastatic melanoma, presumed secondary from a melanoma excised from the patient’s back 2 years previously. During surgery intended to resect the gastric lesion, peritoneal nodularity was identified, with histology confirming metastatic pancreas cancer. This case highlights two main points of interest. Firstly it emphasises the role for consideration of a genetic predisposition in young patients with more than one primary malignancy. The man in this case was not informed of his family history as he was adopted. If he had knowledge of previous family history, he may have been able to provide information to expedite arrival at the diagnosis of a CDKN2A mutation (melanoma-pancreatic carcinoma syndrome). In addition, this case also raises the issue of the challenges we face when treating synchronous primary malignancies. The two malignancies here behaved equally aggressively and posed obstacles for treatment as there is no mutual method of carcinogenesis that could be targeted with treatment; therefore, treatment modalities had to be chosen to treat each malignancy separately. To date, studies evaluating the role for targeted therapy in the setting of CDKN2A mutations have not conclusively provided meaningful benefits to patients.
Inappropriate Secretion of Antidiuretic Hormone after Pancreatoduodenectomy for Pancreatic Head Cancer: A Case Report and Literature Review
Authors: Karakuchi Nozomi , Ohmori Ichiro , Inoue Masashi , Toyota Kazuhiro , Takahashi Tadateru
Published: March 2021

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a disease that leads to dilute hyponatremia through excessive secretion of antidiuretic hormone. SIADH has various causes, including ectopic ADH-producing tumors, drug properties, and can be idiopathic. But there have been very few reports of cases in which SIADH has developed after surgery for malignant tumors. In addition, few cases have been reported where this disease has developed after surgery for pancreatic cancer, because the symptoms of hyponatremia are non-specific. These symptoms are particularly gastrointestinal symptoms; therefore, it is difficult to differentiate them, even if SIADH has developed after gastrointestinal surgery. The patient in our case was an 80-year-old woman. She had persistent epigastralgia and left back pain. Imaging studies revealed a tumor in the head of the pancreas, which was diagnosed as pancreatic head cancer. We performed subtotal stomach-preserving pancreatoduodenectomy. After the operation, she complained of appetite loss and general fatigue. Her serum sodium levels decreased to 109 mEq/L on postoperative day 11. She was diagnosed with SIADH using the SIADH diagnostic criteria listed by the Japanese Ministry of Health, Labor and Welfare. We treated the patient with sodium supplementation for hyponatremia, and her symptoms ameliorated. After the event, she did not relapse with hyponatremia. This case is significant in that we performed differential diagnosis after major gastrointestinal surgery for pancreatic cancer and diagnosed SIADH at an early stage.
Retrorectal Mucinous Adenocarcinoma Arising from a Tailgut Cyst: A Case Report
Authors: Baverez Manon , Thibaudeau Emilie , Libois Vincent , Kerdraon Olivier , Senellart Hélène , Raoul Jean-Luc
Published: March 2021

We report the case of a 57-year-old woman who presented with local invasion of the anal canal by mucinous adenocarcinoma, the malignant transformation of a long-term preexisting retrorectal tailgut cyst. This progression is infrequent and justifies preemptive surgical treatment of retrorectal cysts.
Febuxostat Attenuates the Progression of Periodontitis in Rats
Authors: Nessa Naseratun , Kobara Miyuki , Toba Hiroe , Adachi Tetsuya , Yamamoto Toshiro , Kanamura Narisato , Pezzotti Giuseppe , Nakata Tetsuo
Published: March 2021

Introduction: Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects. Objective: The present study investigated the effects of febuxostat on periodontitis in a rat model. Methods: Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined. Results: In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-α, IL-1β, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations. Conclusion: Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.
Effects of COVID-19 Pandemic on the Treatment of Pancreatic Cancer: A Perspective from Central Europe
Authors: Pergolini Ilaria , Demir I. Ekin , Stöss Christian , Emmanuel Klaus , Rosenberg Robert , Friess Helmut , Novotny Alexander
Published: March 2021

Background: This survey aimed to register changes determined by the COVID-19 pandemic on pancreatic surgery in a specific geographic area (Germany, Austria, and Switzerland) to evaluate the impact of the pandemic and obtain interesting cues for the future. Methods: An online survey was designed using Google Forms focusing on the local impact of the pandemic on pancreatic surgery. The survey was conducted at 2 different time points, during and after the lockdown. Results: Twenty-five respondents (25/56) completed the survey. Many aspects of oncological care have been affected with restrictions and delays: staging, tumor board, treatment selection, postoperative course, adjuvant treatments, outpatient care, and follow-up. Overall, 60% of respondents have prioritized pancreatic cancer patients according to stage, age, and comorbidities, and 40% opted not to operate high-risk patients. However, for 96% of participants, the standards of care were guaranteed. Discussion/Conclusions: The first wave of the COVID-19 pandemic had an important impact on pancreatic cancer surgery in central Europe. Guidelines for prompt interventions and prevention of the spread of viral infections in the surgical environment are needed to avoid a deterioration of care in cancer patients in the event of a second wave or a new pandemic. High-volume centers for pancreatic surgery should be preferred and their activity maintained. Virtual conferences have proven to be efficient during this pandemic and should be implemented in the near future.
Spontaneous Pneumothorax as a Complication in Concomitant Diabetic Ketoacidosis and Pulmonary Tuberculosis: A Case Report
Authors: Adlar Filbert Riady , Anthony Willy
Published: March 2021

Secondary spontaneous pneumothorax (SSP) can occur as a complication of several underlying diseases such as pulmonary tuberculosis (TB) or, rarely, diabetic ketoacidosis (DKA). As diabetes mellitus (DM) is significantly prevalent in tuberculosis patients, it is possible to have both TB and DKA concurrently. However, there has not been any documentation of SSP as a complication in concomitant DKA and pulmonary TB. In this report, we described a 30-year-old female who presented to the emergency department with a chief complaint of shortness of breath that had intensified since a day before. She was diagnosed with pulmonary TB 1 week before and had started on her anti-tuberculosis drugs regimen. Prior history of DM was not known. Physical examination showed a slight decrease in consciousness, tachycardia, tachypnea, Kussmaul breathing, decreased lung sounds in the right hemithorax and hyperresonant on percussion. Laboratory results showed leukocytosis and hyperglycemia, ketones were positive on urinalysis and arterial blood gas analysis indicated metabolic acidosis. Chest X-ray revealed pneumothorax in the right hemithorax. She was diagnosed with pneumothorax of the right hemithorax, DKA, sepsis and pulmonary TB. Treatment involved prompt placement of chest tube drainage, fluid rehydration, intravenous insulin, antibiotic, sodium bicarbonate and anti-tuberculosis drugs. Her condition improved after 9 days of uneventful hospitalization. We discussed how concomitant presence of both DKA and pulmonary TB can increase the likelihood of developing secondary spontaneous pneumothorax.
Expanded Hemodialysis and Its Effects on Hospitalizations and Medication Usage: A Cohort Study
Authors: Sanabria Rafael M. , Hutchison Colin A. , Vesga Jasmin I. , Ariza Juan G. , Sanchez Ricardo , Suarez Adriana M.
Published: March 2021

Introduction: Expanded hemodialysis (HDx) effectively removes large middle molecular uremic toxins (>25 kDa) while still retaining albumin, potentially reducing their adverse effects. We compare the clinical laboratory parameters, hospitalization rates, and medication use in a cohort of patients switched from high-flux HD to HDx. Methods: This is a multicenter, observational cohort study of 81 adult patients, across 3 clinics, with end-stage kidney disease (ESKD) on chronic hemodialysis (HD). Patients received high-flux HD for at least 1 year and then switched to HDx and were followed up for 1 year. Patients were excluded if they discontinued therapy, changed provider, underwent kidney transplant, recovered kidney function, or changed to peritoneal dialysis, another dialyzer, or renal clinic. Results: Twelve months after switching to HDx, the rate of hospitalization events per patient-year decreased from 0.77 (95% CI: 0.60–0.98, 61 events) to 0.71 (95% CI: 0.55–0.92, 57 events) (p = 0.6987). The hospital day rate per patient-year was significantly reduced from 5.94 days in the year prior to switching compared with 4.41 days after switching (p = 0.0001). The mean dose of erythropoiesis-stimulating agent (SC epoetin-α) and intravenous iron also significantly decreased (p = 0.0361 and p = 0.0003, respectively). Conclusion: Switching to HDx was associated with reductions in hospital day rate and medication use, suggesting HDx has the potential to reduce the burden of ESKD on patients and healthcare systems.
Abrupt Aggravation of Encapsulated Seroma after Breast Reconstruction with Extended Latissimus Dorsi Muscle Flap
Authors: Tanaka Kiyomi , Oura Shoji , Yasuda Koji , Makimoto Shinichiro
Published: March 2021

A 57-year-old woman underwent salvage nipple-preserving mastectomy with immediate breast reconstruction using extended latissimus dorsi muscle flap for her in-breast recurrence. The patient had been well with a presumed encapsulated seroma in her back for 8 years and 3 months but suddenly developed a protrusion of the persistent seroma. The patient requested us to improve the cosmetic deterioration of the visible large protrusion. In the operation, the operative target was converted from the newly protruded portion to the whole persistent seroma due to the leakage of presumed contaminated fluid. The posterior wall of the long-lasting seroma sticked rigidly to the ribs, forcing us not to resect the whole capsule but to resect the anterior and lateral walls with scraping the posterior wall with a curet. Pathological study showed a dense fibrous capsule, amorphous eosinophilic material, cholesterin crystals, and massive histiocyte infiltration. Postoperative course was uneventful, but wound healing was not observed over 3 weeks after operation. Minocycline 100 mg diluted in 20 mL saline was injected into the seroma cavity after full aspiration of the seroma fluid, causing immediate irritable sensation around the seroma cavity and complete disappearance of the seroma cavity in 3 weeks after the minocycline injection. Pathogenesis of this extremely rare complication remains uncertain, but long-lasting seroma formation should be avoided not to cause this type of late-phase complication. Minocycline injection into the seroma cavity is a feasible method to accelerate the wound healing.
Glioma with Leptomeningeal Spread Mimics Chronic Meningoencephalitis in a Young Adult
Authors: Becker Ann-Kristin , Frank Marta Leonora , Friese Michael , Röther Joachim
Published: March 2021

The most malignant type of intrinsic brain tumor is glioblastoma (WHO grade IV). Primary leptomeningeal spread is rare and leads to a variety of differential considerations, as there is no typical clinical or imaging pattern. Here we present a rare and uncommon case of a primary leptomeningeal glioblastoma in combination with a low-grade glioma in a 21-year-old male, initially presenting with only headache and lower back pain. The presented case illustrates the challenging differential considerations and the severe course of leptomeningeal glioblastomas.
Ovarian Dysgerminoma in Pregnant Women with Viable Fetus: A Rare Case Report
Authors: Youssef Reda , Ahmed Gamal Sayed , Alhyassat Samir , Badr Sanaa , Sabry Ahmed , Kohla Samah
Published: March 2021

Dysgerminoma is an uncommon malignant tumor arising from the germ cells of the ovary. Its association with pregnancy is extremely rare, with a reported incidence of about 0.2–1 per 100,000 pregnancies. Women in the reproductive age group are more commonly affected. It can be extremely rare to conceive naturally, without assisted reproductive interventions, in cases with ovarian dysgerminoma. If a pregnancy does occur with a concurrent dysgerminoma, it is even more unusual to carry the pregnancy to viability or childbirth without fetal or maternal compromise. We report a case of right ovarian dysgerminoma in a young female with a viable intrauterine pregnancy at 10 weeks, which is rarely diagnosed and managed at this gestational age. Numerous factors played a role in her favorable outcome, including early suspicion by ultrasound and presenting history, surgery, histopathological assessment, imaging, and involvement of the multidisciplinary oncology team. Ovarian neoplasms may rapidly increase in size within a short period with little or no symptoms. This poses a diagnostic challenge for obstetricians and oncologists. Hence, we aimed to evaluate the role of imaging in pregnancy using ultrasound as an imaging modality for both early detection of ovarian neoplasms and for follow-up. In conclusion, patients with ovarian dysgerminoma in pregnancy can have favorable outcomes. Treatment should be individualized on a case-to-case basis, depending on many factors; cancer stage, previous reproductive history, the impact of imaging in staging or follow-up of tumor on the fetus, fetal gestational age, and whether termination of the pregnancy can improve survival or morbidity for the mother.
Contingent Tunes of Neurochemical Ensembles in the Norm and Pathology: Can We See the Patterns?
Authors: Trofimova Irina
Published: March 2021

Background/Aims: Progress in the development of DSM/ICD taxonomies has revealed limitations of both label-based and dimensionality approaches. These approaches fail to address the contingent, nonlinear, context-dependent, and transient nature of those biomarkers linked to specific symptoms of psychopathology or to specific biobehavioural traits of healthy people (temperament). The present review aims to highlight the benefits of a functional constructivism approach in the analysis of neurochemical biomarkers underlying temperament and psychopathology. Method: A review was performed. Results: Eight systems are identified, and 7 neurochemical ensembles are described in detail. None of these systems is represented by a single neurotransmitter; all of them work in ensembles with each other. The functionality and relationships of these systems are presented here in association with their roles in action construction, with brief examples of psychopathology. The review introduces formal symbols for these systems to facilitate their more compact analysis in the future. Conclusion: This analysis demonstrates the possibility of constructivism-based unifying taxonomies of temperament (in the framework of the neurochemical model functional ensemble of temperament) and classifications of psychiatric disorders. Such taxonomies would present the biobehavioural individual differences as consistent behavioural patterns generated within a formally structured space of parameters related to the generation of behaviour.
Topical Applications of a Heparinoid-Containing Product Attenuate Glucocorticoid-Induced Alterations in Epidermal Permeability Barrier in Mice
Authors: Wen Si , Wu Jiangmei , Ye Li , Yang Bin , Hu Lizhi , Man Mao-Qiang
Published: March 2021

Introduction: Either systemic or topical glucocorticoids (GCs) can cause significant adverse effects on cutaneous structure and function. Although some products and ingredients can improve GC-induced abnormalities in epidermal permeability barrier, the efficacy is moderate. Prior studies in normal mice showed that topical applications of a heparinoid-containing product, Hirudoid® cream, improve epidermal barrier function by upregulation of epidermal proliferation, expression of mRNA for epidermal differentiation, and lipid production. Objective: The objective of this study was to assess whether topical applications of this product could prevent GC-induced changes in epidermal function in murine skin. Materials and Methods: One group of C57BL/6J mice was treated topically with 0.05% clobetasol propionate twice daily for 6 days, while another group was treated topically with Hirudoid® cream 30 min after each application of clobetasol propionate. Untreated mice served as normal controls. Transepidermal water loss (TEWL) rates, stratum corneum hydration, and skin surface pH were measured using respective probes connected to an MPA5 physiology monitor. qPCR was used to measure the expression levels of mRNA for keratinocyte differentiation-related proteins and lipid synthetic enzymes. Results: Co-applications of Hirudoid® cream with GC minimally, but significantly, increased skin thickness in comparison to GC treatment alone (p < 0.05), in parallel with increased expression levels of mRNA for PCNA in both the dermis and the epidermis. Moreover, Hirudoid® cream largely prevented GC-induced elevation in basal TEWL (p < 0.001) and delay in barrier recovery (p < 0.05), accompanied by upregulation in the expression levels of mRNA for epidermal involucrin, HMGCoA, and SPT1. However, both stratum corneum hydration and skin surface pH were comparable in the skin treated with GC alone versus GC + Hirudoid® cream. Conclusion: Topical heparinoid-containing product can partially prevent GC-induced alterations in some epidermal functions.
Hepatic Epithelioid Hemangioendothelioma Presenting Synchronously with Hepatocellular Carcinoma
Authors: Kanno Hiroki , Sato Toshihiro , Midorikawa Ryuta , Kojima Satoki , Fukutomi Shogo , Goto Yuichi , Nomura Yoriko , Yoshitomi Munehiro , Kawahara Ryuichi , Sakai Hisamune , Hisaka Toru , Akagi Yoshito , Okuda Koji
Published: March 2021

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant tumor with unknown pathogenesis. Herein, we report a case of a hepatic EHE presenting synchronously with a hepatocellular carcinoma (HCC). To the best of our knowledge, this is the second case report of synchronous hepatic EHE and HCC. An 84-year-old man presented with back pain. During examination, a tumor in liver segment 3 was coincidentally detected. Tumor marker (carbohydrate antigen 19-9, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II) levels were elevated. Contrast-enhanced computed tomography revealed perinodular enhancement in the arterial and portal phases. Another tumor was detected in liver segment 2, which was homogeneously enhanced in the arterial phase, followed by washout in the portal and late phases. Based on these imaging findings, we diagnosed the tumor in segment 3 as a solitary cholangiocellular carcinoma and the tumor in segment 2 as a solitary HCC. Lateral sectionectomy of the liver was performed. Microscopically, spindle-shaped and epithelioid cells were present in the tumor in segment 3. On immunohistochemistry, the tumor cells were positive for CD31 and CD34, focally positive for D2-40, and negative for AE1/AE3. Therefore, the tumor in segment 3 was ultimately diagnosed as an EHE and the tumor in segment 2 as a well-differentiated HCC. Preoperative diagnosis of EHE is difficult owing to the lack of specific findings. Intratumoral calcification, halo sign, and lollipop sign are occasionally found in EHE and are useful imaging findings for diagnosis. Clinical behavior is unpredictable, ranging from indolent growth to rapid progression. Clinical or pathological predictors of the course of EHE are urgently required.
Study Protocol for the Use of Conventional Open Haemorrhoidectomy versus Laser Haemorrhoidoplasty in the Treatment of Symptomatic Haemorrhoids: A Randomized Controlled Trial
Authors: Koh Frederick H. , Foo Fung Joon , Ho Leonard , Sivarajah Sharmini S. , Tan Winson J. , Chew Min-Hoe
Published: March 2021

Background: Haemorrhoids result in a variety of symptoms that cause significant patient anxiety. Treatment has long been associated with post-operative complications, which cause significant symptoms and may result in readmissions. The open conventional haemorrhoidectomy (COH) is still regarded as the gold standard treatment for non-circumferential grade II–IV haemorrhoids. Laser haemorrhoidoplasty (LAH) has recently been studied and the initial results appear promising. This study aims to compare these 2 techniques in the treatment of symptomatic haemorrhoids. We hypothesize that LAH has significantly less pain and bleeding and better quality of life (QoL) scores 1, 3 and 12 months post-operatively. Methods: A prospective, randomized, double-blind, single-centre clinical trial will be conducted. All patients aged between 21 and 90 years who present with symptomatic grade II–IV haemorrhoids will be recruited. Exclusion criteria include those who have had previous operations for haemorrhoids and those with an increased risk of bleeding. Data collected will include patient demographics, pre- and intra-operative characteristics of the haemorrhoids, operative details and post-operative pain Visual Analogue Scale (VAS) score, complications, readmissions, and haemorrhoid-specific QoL surveys. Primary outcome will be median post-operative pain VAS score on post-operative days (POD) 1–10. Secondary outcomes include operative duration, bleeding on the first 10 days post-operatively, readmissions, procedure-related complications (fistulation, incontinence, stenosis), QoL scores, and recurrence of symptoms up to 12 months. Discussion: Results from this trial may demonstrate the superiority of LAH over COH in terms of post-operative pain and recovery. This would likely increase the adoption of LAH for the treatment of symptomatic haemorrhoids. Trial Registration: This trial was registered on 1/4/2020 at ClinicalTrials.gov. URL: https://www.clinicaltrials.gov/ct2/show/NCT04329364?term=NCT04329364&draw=2&rank=1.