bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipose-Derived Stromal/Stem Cell Culture: Effects of Different Concentrations of Human Platelet Lysate in Media
Authors: Ballesteros Olga R. , Brooks Patrick T. , Haastrup Eva K. , Fischer-Nielsen Anne , Munthe-Fog Lea , Svalgaard Jesper D.
Published: March 2021

Adipose-derived stromal/stem cells (ASCs) are being tested as a possible treatment for a wide range of diseases to exploit the immunomodulatory and regenerative potential demonstrated in vitro. Pooled human platelet lysate (pHPL) has replaced fetal bovine serum (FBS) as the preferred growth supplement because of its xeno-free origin and improved cell proliferation. Much has been done toward reducing the concentration of pHPL required when expanding ASCs. However, little is known on how increasing the concentration of pHPL affects ASC potency, which could lead to changes with possible beneficial applications. This study investigated the effect of 5, 10, or 20% pHPL in culture media on ASC proliferation and phenotypic marker expression, including chemokine receptors CXCR2, CXCR3, CXCR4, and VLA-4. Adipogenic and osteogenic properties, as well as immunosuppressive properties, including the ability to induce indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) and suppress T cell proliferation, were also examined. We observed a significant increase in cell yield (approximately 2-fold) and a corresponding reduction in population doubling time and cell volume when doubling the concentration of pHPL in the growth media. ASCs maintained expression of phenotypic surface markers CD73, CD90, and CD105 and were negative for CD45 and CD31. The ability to induce IDO1 and suppress T cell proliferation was observed as well. Adipogenesis and osteogenesis, however, seem to be increased at higher concentrations of pHPL (20% > 10% > 5%), while expression of chemokine receptors CXCR2 and CXCR3 was lower. In conclusion, increasing the pHPL concentration to 20% could be used to optimize culture conditions when producing cells for clinical treatments and may even be used to enhance beneficial ASC properties depending on the desired therapeutic effect.
The Association among Pyoderma Gangrenosum, Ulcerative Colitis, and Hidradenitis Suppurativa and the Syndromic Hidradenitis Suppurativa Network: A Case Report
Authors: Bettoli Vincenzo , Schettini Natale , Libanore Marco , Scuderi Valeria , Zedde Pierantonia , Forconi Riccardo , Pacetti Lucrezia , Ceccherini Isabella , Gattorno Marco , Poggioli Gilberto , Corazza Monica
Published: March 2021

Hidradenitis suppurativa (HS), together with other inflammatory diseases, is involved in a syndromic network where different combinations of signs and symptoms characterize the definition. The observation of the concurrent occurrence of HS, pyoderma gangrenosum (PG), and inflammatory bowel disease (IBD), in detail ulcerative colitis (UC), led the authors to describe a new association. The patient, a 36-year-old woman, who saw IBD as the first appearing condition, shortly followed by HS and PG, was referred because of a clinical situation quickly worsening. A severe aggravation of both GI symptoms and general systemic situation total led to total colectomy. Surprisingly, shortly after the radical surgical treatment of UC, the cutaneous manifestations of HS and PG with no specific treatment almost completely disappeared suggesting the existence of a common etiopathogenetic mechanism and possibly an inductor role of UC on the other disorders. The presentation of this case offers the opportunity to deal with the fact that the resolution of one of the associated conditions may lead to the clearance of one or more of the others. It confirms a pathogenetic link between them and the pivotal role of one of them, in this case colitis.
Soluble ST2 and Galectin-3 as Predictors of Chronic Kidney Disease Progression and Outcomes
Authors: Kim Ae Jin , Ro Han , Kim Hyunsook , Chang Jae Hyun , Lee Hyun Hee , Chung Wookyung , Jung Ji Yong
Published: March 2021

Background: Soluble suppression of tumorigenicity-2 (sST2) and galectin-3, novel biomarkers of heart failure and cardiovascular stress, predict cardiovascular events (CVEs) and mortality. However, their relationship with kidney function and adverse outcomes in CKD are uncertain. The purpose of this study was to determine the association between sST2 and galectin-3 with CKD progression and adverse clinical outcomes. Methods: We measured baseline sST2 and galectin-3 levels in the CKD patient cohort at our institution between October 2013 and December 2014. The primary outcome was CKD progression (kidney failure with replacement therapy or ≥50% reduction in estimated glomerular filtration rate from the baseline). The secondary outcome was the composite of CVEs and death. We used a Cox proportional hazards model to evaluate the associations between sST2 and galectin-3 levels, with kidney and clinical outcomes. Results: In total, 352 patients were enrolled in this study. At baseline, log sST2 and galectin-3 were directly associated with the serum creatinine (Cr) and urine protein-to-Cr ratio. Cox regression analysis showed that the baseline log sST2 level independently predicted CKD progression and composite outcome after adjustment for age, sex, smoking, diabetes mellitus, hypertension, cardiovascular disease, renin-angiotensin system blocker, calcium channel blocker, β-blocker, diuretics, antiplatelet agents, anemia, and hypoalbuminemia. The baseline log galectin-3 level was independently associated with CKD progression, but not with the composite outcome after adjustment for confounding variables. Conclusions: Elevated levels of sST2 and galectin-3 are significantly associated with CKD progression, but only sST2 is associated with adverse clinical outcomes.
Early Acute Kidney Injury in Preterm and Term Neonates: Incidence, Outcome, and Associated Clinical Features
Authors: Gallo Dario , de Bijl-Marcus Karen A. , Alderliesten Thomas , Lilien Marc , Groenendaal Floris
Published: March 2021

Background: Critically ill neonates are at high risk of kidney injury, mainly in the first days of life. Acute kidney injury (AKI) may be underdiagnosed due to lack of a uniform definition. In addition, long-term renal follow-up is limited. Objective: To describe incidence, etiology, and outcome of neonates developing AKI within the first week after birth in a cohort of NICU-admitted neonates between 2008 and 2018. Renal function at discharge in infants with early AKI was assessed. Methods and Subjects: AKI was defined as an absolute serum Cr (sCr) value above 1.5 mg/dL (132 μmol/L) after the first 24 h or as stage 2–3 of the NIDDK neonatal definition. Clinical data and outcomes were collected from medical records and retrospectively analyzed. Results: From January 2008 to December 2018, a total of 9,376 infants were admitted to the NICU of Wilhelmina Children’s Hospital/UMC Utrecht, of whom 139 were diagnosed with AKI during the first week after birth. In 72 term infants, the most common etiology was perinatal asphyxia (72.2%), followed by congenital kidney and urinary tract malformations (CAKUT) (8.3%), congenital heart disease (6.9%), and sepsis (2.8%). Associated conditions in 67 preterm infants were medical treatment of a hemodynamic significant PDA (27.2%), ­CAKUT (21%), and birth asphyxia (19.4%). Among preterm neonates and neonates with perinatal asphyxia, AKI was mainly diagnosed by the sCr >1.5 mg/dL criterion. Renal function at discharge improved in 76 neonates with AKI associated with acquired conditions. Neonates with stage 3 AKI showed increased sCr values at discharge. Half of these were caused by congenital kidney malformations and evolved into chronic kidney disease (CKD) later in life. Neurodevelopmental outcome (NDO) at 2 years was favorable in 93% of surviving neonates with detailed follow-up. Conclusion: During the first week after birth, AKI was seen in 1.5% of infants admitted to a level III NICU. Renal function at discharge had improved in most neonates with acquired AKI but not in infants diagnosed with stage 3 AKI. Long-term renal function needs further exploration, whereas NDO appears to be good.
Infection with Hepatitis B Virus May Increase the Serum Concentrations of Osteopontin
Authors: Liu Hua-Bing , Chen Qin-Yan , Wang Xue-Yan , Zhang Lu-Juan , Hu Li-Ping , Harrison Tim J. , Wang Chao , Fang Zhong-Liao
Published: March 2021

Background: Serum osteopontin (OPN) concentrations were found to be significantly increased in patients infected with hepatitis B virus (HBV) and patients with hepatocellular carcinoma (HCC). Objective: The aim of this study was to determine the association among HCC, OPN, and HBV. Methods: Two hundred and forty-one subjects were recruited and divided into 6 groups: healthy controls, asymptomatic HBsAg carriers, HBsAg (−) patients with other tumors, HBsAg (+) chronic liver disease patients, HBsAg (+) patients with HCC, and HBsAg (−) patients with HCC or liver cirrhosis (LC). Serum concentrations of OPN and HBsAg were measured and analyzed. Results: OPN concentrations in the HBsAg (+) HCC group were significantly higher than the healthy control group and the HBsAg (−) patients with other cancers (both p = 0.0001). The OPN concentrations of the HBsAg (−) patients with HCC or LC also did not differ significantly from those of the healthy control group (p = 0.075). There is a correlation between the titer of HBsAg and concentrations of OPN in all 3 HBsAg (+) groups (all p values <0.05). Conclusions: Infection with HBV may increase the serum concentrations of OPN. The association of OPN and HCC may be not attributable to tumor development per se but, rather, to HBV infection.
Clinical Factors Associated with the Risk of Intracranial Aneurysm Rupture in Autosomal Dominant Polycystic Kidney Disease
Authors: Lee Chan-Hyuk , Ahn Curie , Ryu Hyunjin , Kang Hyun-Seung , Jeong Seul-Ki , Jung Keun-Hwa
Published: March 2021

Background: The occurrence of intracranial aneurysms is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the healthy population. However, research concerning the factors related to the risk of intracranial aneurysm rupture in patients with ADPKD is still insufficient. Objectives: The aim of the study was to investigate the prevalence of intracranial aneurysms and aneurysmal subarachnoid hemorrhage (SAH) and to analyze the systemic factors associated with high-risk aneurysms in patients with ADPKD. Methods: We screened patients who underwent cerebral angiography between January 2007 and May 2017 in the ADPKD registry. Patients were examined for the presence of intracranial aneurysms and subsequently reclassified into 3 groups based on the risk of aneurysmal rupture: the aneurysm-negative (group 1), low-risk aneurysm (group 2), or high-risk aneurysm (group 3). Various systemic factors were compared, and independent factors associated with high-risk aneurysms were analyzed. Results: Among the 926 patients, 148 (16.0%) had intracranial aneurysms and 11 (1.2%) had previous aneurysmal SAH. Patients with intracranial aneurysms were further classified into group 2 (low-risk aneurysms, 15.5%) or group 3 (high-risk aneurysms, 84.5%). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01–1.05, p = 0.004), female sex (OR 3.13, 95% CI 1.94–5.0 6, p < 0.001), dolichoectasia (OR 8.57, 95% CI 1.53–48.17, p = 0.015), and mitral inflow deceleration time (DT) (OR 1.01, 95% CI 1.00–1.01, p = 0.046) were independently associated with high-risk aneurysms, whereas hypercholesterolemia (OR 0.46, 95% CI 0.29–0.72, p = 0.001) was negatively associated. Conclusion: In the present study among patients with ADPKD, the prevalence of intracranial aneurysms and aneurysmal SAH was 16 and 1.2%, respectively. Age, female sex, dolichoectasia, and mitral inflow DT were positively associated with high-risk aneurysms, whereas hypercholesterolemia was negatively associated. A subsequent large-scaled longitudinal study is needed to define the plausibility of the clinical parameters.
The Factor Structure of Items Assessing Subjective Memory: Between-Persons and Within-Persons across Time
Authors: Mogle Jacqueline , Hill Nikki L. , Bell Tyler Reed , Bhargava Sakshi , Bratlee-Whitaker Emily
Published: March 2021

Introduction: Current understanding of the psychometric properties of items intended to assess the multidimensional construct of subjective memory (SM) is limited, as longitudinal studies of aging commonly use single items or brief sets of items to assess SM. Investigating how SM items cluster within individuals over time would increase the understanding of how combining these items impacts their utility as an early indicator of cognitive change in the aging trajectory. To address this need, the current study examined the factor structure of a brief set of SM items in an existing longitudinal study focused on cognitive aging at both the within-person and between-person levels. Methods: Data were drawn from the Einstein Aging Study, a longitudinal cohort study of aging (N = 1,239, Mage = 77.51, SD = 5.03; 69.50% white; 24.27% black; 6.23% other). Community-dwelling older adults from an urban area of New York City were interviewed annually. At each wave, participants responded to 6 items intended to assess SM. Items assessed participants’ perceived memory decline as well as current memory ability. Multilevel exploratory factor analyses examined which factor solution best fit the data at between-person and within-person levels. Results: Factor structure of the SM items varied at the two levels. At the within-person level, two factors emerged, whereas at the between-person level, a single factor best represented the SM items. Items assessing perceived declines in memory functioning tended to have similar trajectories, while items assessing current memory ability were less related to change over time. Conclusion: Items appeared to assess two different dimensions of SM when examining within-person changes in SM across time; however, the item structure suggested no other items covaried systematically within persons over time. In contrast to the conceptualization of SM as a multidimensional construct, our findings suggest that when measuring SM between individuals, SM items tend to capture a single dimension underlying SM. This may be due to the long retrospection period of items assessing perceived memory ability. A single item assessing perceived memory decline in older adults without evidence of objective cognitive impairment may be sufficient to monitor memory change in clinical or research settings.
COVID-19 Barometer: Social Opinion – What Do the Portuguese Think in This Time of COVID-19?
Authors: Pedro Ana Rita , Gama Ana , Soares Patrícia , Moniz Marta , Laires Pedro A. , Dias Sónia
Published: March 2021

The COVID-19 pandemic brought new challenges to the global community, reinforcing the role of public health in society. The main measures to combat it had (and still have) a huge impact on the daily lives of citizens. This investigation aimed to identify and monitor the population’s perceptions about how it faced this period and the impact on health, well-being, and daily life. In this study, we describe the main trends observed throughout the COVID-19 pandemic in terms of mental health status, confidence in the capacity of the health services to respond to the pandemic, and the use of health services by participants. The online survey collected responses from 171,947 individuals ≥16 years of age in Portugal, over a period of 15 weeks that started on 21 March 2020. Participants could fill the questionnaire once or weekly, which enabled us to analyse trends and variations in responses. Overall, 81% of the respondents reported having felt agitated, anxious, or sad during the COVID-19 pandemic; 19% did not experience these feelings. During the confinement period, the proportion of participants feeling agitated, anxious, or sad every day/almost every day ranged between 20 and 30%, but since the deconfinement this proportion decreased. Around 30% reported having more difficulty getting to sleep or to sleep all night; 28.4% felt more agitated; 25.5% felt sadder, discouraged, or cried more easily; and 24.7% felt unable to do everything they had to do, women more frequently than men. Overall, 65.8% of the participants reported feeling confident or very confident in the health services’ capacity to respond to the challenges associated with the pandemic, and this confidence increased over time. Concerning the people who needed a consultation, 35.6% had one in person and 20.8% had one remotely, but almost 44% did not have one due to cancellation by the service (27.2%) or their own decision not to go (16.3%). At this unusual time in which we find ourselves and based on our findings, it is essential to continue monitoring how the population is facing the different phases of the pandemic until it officially ends. Analysing the effects of the pandemic from the point of view of citizens allows for anticipating critical trends and can contribute to preventative action.
Prestroke Statins Improve Prognosis of Atrial Fibrillation-Associated Stroke through Increasing Suppressor of Cytokine Signaling-3 Levels
Authors: Lu Taoli , Yang Xu , Cai Yanli , Xie Chenchen , Zhang Bei
Published: March 2021

Background: Cerebral infarction associated with atrial fibrillation (AF) has relatively higher mortality and morbidity rates than other types of stroke. Statins are being commonly prescribed to patients with stoke. However, the use of statins in AF-related stroke, especially prestroke, has not been well studied. This study aimed to investigate whether the use of prestroke statins could improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS) and its mechanism. Methods: This prospective study enrolled 453 AF-associated AIS patients from 4 medical centers and divided them into 2 groups based on the statin use before the stroke episode. All patients received comprehensive clinical examinations including 72-h Holter electrocardiogram monitoring and were followed up for 3 months. Plasma suppressor of cytokine signaling-3 (SOCS-3) and matrix metalloproteinase-9 (MMP-9) levels were measured by ELISA on admission and days 3 and 7 after enrollment. The endpoints were death, major disability (modified Rankin Scale score ≥3), and composite outcome (death/major disability) at 3 months after the AIS episode. Results: Plasma SOCS-3 levels were significantly increased and MMP-9 levels decreased in patients in the prestroke statin group on hospital admission and days 3 and 7 after enrollment (p < 0.001). Furthermore, our data suggested that baseline plasma SOCS-3 levels were associated with increased risk of 3-month mortality (adjusted odds ratio [OR], 1.012; 95% confidence interval [CI], 1.006–1.018; p < 0.001) and major disability (adjusted OR, 1.013; 95% CI, 1.007–1.02; p < 0.001). Similarly, baseline plasma MMP-9 levels were also associated with increased risk of 3-month mortality (adjusted OR, 1.037; 95% CI, 1.022–1.053; p < 0.001) and major disability (adjusted OR, 1.038; 95% CI, 1.022–1.55; p < 0.001). Conclusion: Our data suggested that the prestroke use of statins improved the clinical outcomes in AIS patients with AF by upregulating the level of SOCS-3 and reducing the plasma MMP-9 level.
Bibliometric Analysis of the 50 Most Cited Publications in Hidradenitis Suppurativa
Authors: Seivright Justine R. , Thompson Alyssa M. , Villa Natalie M. , Shi Vivian Y. , Hsiao Jennifer L.
Published: March 2021

Background: Hidradenitis suppurativa (HS) has historically been a neglected disease. However, research in this field has grown exponentially in the past decade. Methods: The top-cited HS articles from 1950 to 2020 were analyzed for authorship, study topic, study design, and senior author country of origin. Results: We found that nearly half of the top 50 cited articles were published in the last decade, with a recent increase in the number of highly cited randomized controlled trials. Medical treatment is the most cited topic, with more attention on biologics over time. The past decade has seen an increase in highly cited articles on HS comorbidities, pathogenesis, and clinical practice guidelines. There has been a predominance of highly cited HS research from Europe; highly cited studies from Africa, Asia, Australia, and South America are lacking. Conclusions: Recent advances in HS research have focused on investigating HS pathogenesis and drug development, highlighting disease comorbidities, and improving evidence-based care. Studies in pathogenesis have translated into a paradigm shift in medical treatment from antibiotics to incorporation of targeted therapies in recent years. Encouraging growth of HS research in countries outside of North America and Europe may help to optimize HS care globally.
Recent Advances in Allergen-Specific Immunotherapy as Treatment for Allergic Asthma: A Practical Overview
Authors: Tabar Ana I. , Delgado Julio , González-Mancebo Eloina , Arroabarren Esozia , Soto Retes Lorena , Domínguez-Ortega Javier ,   Spanish Allergy and Clinical Immunology Scientific Society (SEAIC)
Published: March 2021

The Global Initiative for Asthma Report updated in 2019 stated that potential benefits of allergen immunotherapy (AIT), compared to pharmacological and avoidance options, must be weighed against the risk of adverse effects and the inconvenience and cost of the prolonged course of therapy in asthma. Thus, with the aim of clarifying some aspects with regard to the possible use of AIT in allergic asthma treatment armamentarium, a group of expert allergists from the Spanish Allergy and Clinical Immunology Scientific Society (SEAIC), particularly from the Immunotherapy and Asthma Interest Groups developed a frequently asked questions in clinical practice. This document updates relevant topics on the use of AIT in asthma and could facilitate physician clinical decisions and improve health outcomes for individual patients.
Gamma Knife Radiosurgery of Distal Aneurysm: A Case Series
Authors: Liscak Roman , Vymazal Josef , Chytka Tomas
Published: March 2021

A series of 3 patients (35–60 years old) with bleeding distal aneurysm not associated with AVM who underwent radiosurgery by gamma knife are reported. One isocentre centralized over the aneurysm was used; peripheral dose 24–28.8 Gy was applied. Control angiography 20–36 months after gamma knife surgery (GKS) demonstrated obliteration of both the aneurysm and the feeding artery, without deterioration of the neurological symptoms. Our case series implies that GKS might serve as a safe mini-invasive technique in the treatment of selected distal aneurysms.
Capecitabine as Maintenance Therapy for High-Risk, Resected Colorectal Cancer
Authors: Auber Miklos L. , Wen Sijin , Hobbs Gerald , Higa Gerald M.
Published: March 2021

Introduction: In 2020, colorectal cancer will be the fourth most frequently diagnosed malignant neoplasm and the second leading cause of site-specific, cancer-related deaths in the USA. Notably, 80% of the new cases are, by staging criteria, potentially curable even those with completely resected stage 4 disease. If slightly more than half the losses can be attributed to metastatic disease at presentation, then the remaining portion of deaths may be linked to disease relapse after surgery and, if applicable, adjuvant chemotherapy. The inference that these therapies are not curative for a significant number of subjects poses a role for maintenance therapy. Objective: To assess event-free survival (EFS) of patients who received capecitabine as maintenance therapy following treatment according to current guidelines. Methods: Clinical outcomes data were collected for 35 subjects treated with capecitabine as maintenance therapy. Descriptive statistical analyses were conducted on collective data related to duration of maintenance therapy and disease or clinical status from surgery to initial event. Kaplan-Meier method and log-rank test were used to analyze EFS and overall survival. Results: Of the entire cohort, 26 subjects have no evidence of disease (NED), a median of 5.5 years from surgery. Kaplan-Meier analyses indicated a 5-year EFS rate of 74% (95% CI: 60–90%). Eighteen of these 26 patients received capecitabine ≥30 months. Eight of the 17 subjects treated with capecitabine therapy for <30 months developed progressive disease; the majority of the relapses occurred within 20 months of surgery. The difference between the two groups was statistically significant. Six subjects died, only two of who had metastatic disease at the time of death; the other four had NED at least 4 years from surgery. Five patients with resected stage 4 disease who received capecitabine as maintenance therapy were alive >5 years from surgery. Conclusion: The findings and analyses of this cohort of patients suggest that maintenance capecitabine therapy reduces the risk of disease progression and cancer-related death.
Hepatocellular Malignant Neoplasm, Not Otherwise Specified: A New Name in Liver Tumors: A Brief Narrative Review of Published Cases
Authors: Geramizadeh Bita , Foroughi Razieh , Shojazadeh Alireza
Published: March 2021

Background: Hepatocellular malignant neoplasm, not otherwise specified (HEM, NOS), is a rare liver tumor that is most commonly seen in adolescents. To the best of our knowledge, there has been no published review on this rare tumor in the English literature so far. Summary: In this review, we will discuss all reported details, including demographic findings, clinical presentations, molecular histogenesis, imaging, gross pathology and histopathology, immunohistochemical findings, treatment modalities, and outcome, of the published cases of HEM, NOS, in the liver. Key Message: Twenty-two cases of HEM, NOS, have been reported in the last 10 years in the English literature. This tumor produces a large liver mass and is characteristically seen in adolescents presenting with right upper quadrant pain. Histologically, HEM, NOS, is a nonbiliary hepatocytic tumor with a biphasic pattern, that is, a mixture of 2 components of hepatocellular carcinoma and hepatoblastoma (HBL). There is no characteristic immunohistochemical feature for this tumor. Imaging findings are also not specific. Treatment of this tumor needs extensive surgery or even liver transplantation. Most of the cases in the literature were treated with the primary diagnosis of HBL, so pathologists, onco-surgeons, and oncologists should get familiar with this tumor to provide better treatment options. More case series with more follow-ups are necessary for the definite determination of the outcome of this tumor as a unique entity.
Pathogenesis of Proteus mirabilis in Catheter-Associated Urinary Tract Infections
Authors: Yuan Fei , Huang Ziye , Yang Tongxin , Wang Guang , Li Pei , Yang Bowei , Li Jiongming
Published: March 2021

Proteus mirabilis (PM) is a Gram-negative rod-shaped bacterium and widely exists in the natural environment, and it is most noted for its swarming motility and urease activity. PM is the main pathogen causing complicated urinary tract infections (UTIs), especially catheter-associated urinary tract infections. Clinically, PM can form a crystalline biofilm on the outer surface and inner cavity of the urethral indwelling catheter owing to its ureolytic biomineralization. This leads to catheter encrustation and blockage and, in most cases, is accompanied by urine retention and ascending UTI, causing cystitis, pyelonephritis, and the development of bladder or kidney stones, or even fatal complications such as septicemia and endotoxic shock. In this review, we discuss how PM is mediated by a catheter into the urethra, bladder, and then rose to the kidney causing UTI and the main virulence factors associated with different stages of infection, including flagella, pili or adhesins, urease, hemolysin, metal intake, and immune escape, encompassing both historical perspectives and current advances.
Surveillance of Employees of Swiss Federal Asylum Centres for Latent Tuberculosis Infection
Authors: Zellweger Jean-Pierre , Zellweger-Landry Ariane , Egger Jean-Marie , Koller-Doser Annette , Schmidt Axel Jeremias
Published: March 2021

Background: Asylum seekers in Switzerland have to register in federal asylum centres (FACs) before formal permission to enter the country. Some of them may have active tuberculosis (TB), exposing fellow refugees and employees. Objectives: The aim of this study was to assess the risk of TB infection among employees of Swiss FACs. Methods: Between 2010 and 2018, a free interferon-gamma release assay (IGRA) was offered to all employees of 8 FACs, at employment and at yearly intervals. We defined latent TB infection as IGRA conversion from negative to positive. IGRA-positive employees were referred to a medical centre for further clinical follow-up. Results: 1,427 tests were performed among 737 employees (54.6% male). 403 (55%) persons were tested only once; 330 (44.5%) were tested several times; for 4 (0.5%) persons, the number of IGRA tests is unknown. Twenty employees (2.7%) had a positive IGRA at baseline, 2 (0.6%) converted from negative to positive during follow-up, resulting in an incidence of 22/10,000 person-years. We observed no case of active TB among employees. Conclusions: The prevalence of latent TB among employees to Swiss FACs and the risk of acquiring TB infection through work-related exposure are low. Yearly IGRA controls in the absence of documented TB exposure seem unnecessary.
Morbidity, Mortality, and Conversion to Neurodegenerative Diseases in Patients with REM Sleep Behavior Disorder and REM Sleep without Atonia
Authors: Asah Cresta , Frandsen Rune , Ibsen Rikke , Kjellberg Jakob , Jennum Poul
Published: March 2021

Introduction: The underlying pathophysiology of idiopathic REM sleep behavior disorder (iRBD) is not fully understood, although the condition is currently recognized as an early-stage alpha-synuclein disorder. We evaluated the morbidity, mortality, and rate of conversion to a neurodegenerative disorder in a national group of patients. Methods: All patients in Denmark with a diagnosis of RBD between 2006 and 2013 were identified from the Danish National Patient Registry (NPR) records. We excluded patients who had received a diagnosis of narcolepsy or any of the following neurodegenerative diseases before their diagnosis of RBD: Parkinson’s disease, multiple system atrophy, progressive supranuclear paralysis, Alzheimer’s, and Lewy body dementia. We used randomly chosen controls matched for age, gender, and municipality. Results: In total, 246 iRBD patients and 982 matched controls were analyzed. The mortality rate was the same in both groups. The morbidity rate was significantly higher in the years before and after an RBD diagnosis, due to a wide variety of disorders in the following major disease groups: mental/behavioral disorders; endocrine/metabolic diseases; diseases of the eye; diseases of the nervous, digestive, musculoskeletal, circulatory, and respiratory systems; abnormal findings not classified elsewhere; external causes; and factors influencing health status. The conversion rate from RBD to a neurodegenerative disease was 13% over the 8 years after a diagnosis of RBD. Conclusions: A diagnosis of RBD is associated with increased morbidity several years before and after a diagnosis is made. Patients have a higher risk of converting to a neurodegenerative disorder than matched controls. Mortality rates are unchanged.
The Time Series Behavior of Neutrophil-to-Lymphocyte Ratio in Thyroid Cancer Patients on Tyrosine Kinase Inhibitor Therapy
Authors: Tomoda Chisato , Sugino Kiminori , Kitagawa Wataru , Nagahama Mitsuji , Ito Koichi
Published: March 2021

Introduction: The neutrophil-to-lymphocyte ratio (NLR) reveals the balance of immune system is and associated with survival in various type of cancers. Tyrosine kinase inhibitors (TKI) improve patient survival with progressing thyroid cancer and are said to have less side effects, and are considered good palliation. Objective: This study evaluated the time series behavior of NLR in advanced thyroid carcinoma patients on TKI therapy and examined what percentage of patients received TKIs in the last month of life. Methods: We retrospectively reviewed medical records on 72 patients with advanced thyroid carcinoma treated with TKIs between May 2015 and October 2018. All patients had progressive disease and/or uncontrolled distant metastasis. Fifty-two patients had differentiated thyroid carcinoma (DTC), 19 patients had anaplastic carcinoma (ATC), and 1 had squamous cell carcinoma. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Median follow-up time in DTC and ATC patients was 12.3 months (range 0.9–40.4) and 2.7 months (range 0.6–14.3), respectively. Results: In DTC patients, median NLR at initial treatment, at initiation of TKI, and for 20 patients who died at the time of death was 2.25 (range, 0.89–9.78), 3.55 (range, 0.86–28.3), and 11.78 (range, 0.98–98.0), respectively. In ATC patients, median NLR at initial treatment, at initiation of TKI, and for 16 patients who died at the time of death was 2.96 (range, 1.12–9.0), 11.43 (range, 2.32–95.0), and 16.9 (range, 3.45–95.0), respectively. NLR >10 at TKI initiation was significantly associated with shorter overall survival compared with NLR <4 and NLR 4–10 (p < 0.0001) in DTC patients. Among 46 dead patients, 32 patients (68.1%) received TKIs treatment in the last month of life (85% DTC patients and 61.5% ATC patients). In receiver operating characteristic curve analysis, cutoffs for DTC and ATC were 11.43 (p = 0.0488, area under the ROC curve 0.941) and 31.67 (p = 0.0034, area under the ROC curve 0.831) in patients who survived ≤6 weeks and >6 weeks, respectively. Conclusion: A substantial percentage of patients received TKIs in the last month of life. The NLR increased according to tumor progression and predicted survival after TKI initiation. We might refer the patients with NLR >11.43 in DTC and those with NLR >31.67 in ATC to a hospice/palliative care program.
Gastric Balloon Implantation as Part of Morbid Adiposity Therapy Changes the Structure of the Stomach Wall
Authors: Patrzyk Maciej , Sonke Jenny , Glitsch Anne , Kessler Rebecca , Steveling Antje , Lünse Sebastian , Partecke Lars Ivo , Heidecke Claus-Dieter , Kessler Wolfram
Published: March 2021

Purpose: The implantation of a gastric balloon (also known as intragastric balloon) is an established and reversible endoscopic procedure for adiposity therapy. Structural changes of the stomach wall are expected to occur with gastric balloon implantation; however, until now these changes have rarely been investigated. Methods: We compared the histological structure of the stomach wall after gastric-sleeve resection in a group of patients following gastric balloon implantation and a group without previous gastric balloon implantation. Results: Following gastric balloon implantation, the tunica muscularis was found to be significantly thicker than without gastric balloon implantation. The enlarging of the tunica muscularis is not caused by hyperplasia of the leiomyocytes, but by hypertrophy of the leiomyocytes and an increase in collagen fibers (fibrosis). Conclusion: A longer-lasting hypertrophy of the tunica muscularis, particularly in the corpus, should be taken into account when surgical treatment follows gastric balloon implantation. The staple suture height should be adjusted to the altered tissue composition since reduced tissue elasticity must be expected due to fibrosis.
Selective Extirpation of Tattooed Lymph Node in Combination with Sentinel Lymph Node Biopsy in the Management of Node-Positive Breast Cancer Patients after Neoadjuvant Systemic Therapy
Authors: Dostalek Lukas , Cerny Andrej , Saskova Petra , Pavlista David
Published: March 2021

Introduction: Axillary dissection has little diagnostic and therapeutic benefit in node-positive breast cancer patients in whom axillary disease has been completely eradicated after neoadjuvant chemotherapy (ypN0). We sought to assess the efficacy of an algorithm used for the identification of the ypN0 patient consisting of intraoperative evaluation of sentinel and tattooed (initially positive) lymph nodes. Methods: Included were T1 and T2 breast cancer patients with 1–3 positive axillary lymph nodes marked with carbon who were referred for neoadjuvant chemotherapy followed by a surgery. Axillary dissection was performed only in the patients with residual axillary disease after neoadjuvant chemotherapy on ultrasound or with metastases described in the sentinel or tattooed lymph nodes either intraoperatively or in the final histology. Results: Out of 62 initially included node-positive patients, 15 (24%) were spared axillary dissection. The detection rate of tattooed lymph nodes after neoadjuvant chemotherapy was 81%. The ypN0 patients were identified with 91% sensitivity and 38% specificity using ultrasound and intraoperative assessment of both sentinel and tattooed lymph node according to the final histology. Discussion/Conclusion: Lymph node marking with carbon dye is a useful and cost-effective method, which can be successfully implemented in order to reduce the number of patients undergoing axillary dissection. Low specificity of the presented algorithm was caused mostly by the overestimation of residual axillary disease on ultrasound.
NEAT1 Is a Novel Oncogenic LncRNA and Correlated with miR-143 in Pediatric Oligodendrogliomas
Authors: Ak Aksoy Secil , Mutlu Melis , Balcin Rabia Nur , Taskapilioglu Mevlut Ozgur , Tekin Cagla , Kaya Seckin , Civan Muhammet Nafi , Kocaeli Hasan , Bekar Ahmet , Eser Ocak Pinar , Cecener Gulsah , Egeli Unal , Tolunay Sahsine , Tunca Berrin
Published: March 2021

Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression ­profiles of microRNA (miRNA) and long noncoding RNA ­(LncRNA) in POGs. Methods: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. Results: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). Discussion: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.
Osteopathic Treatment of Infants in Their First Year of Life: A Prospective Multicenter Observational Study (OSTINF Study)
Authors: Schwerla Florian , Daake Boris , Moeckel Eva , Resch Karl-Ludwig
Published: March 2021

Introduction: In Germany in recent years, a growing number of parents are seeking help from osteopaths for the perceived health complaints of their infants and children. However, reliable evidence for the effectiveness of osteopathic interventions for this group of patients is largely lacking. Objective: To observe and document changes in the symptoms of certain health disturbances, as perceived by parents, during the course of an osteopathic treatment of their baby, and associated side effects. Methods: A single-arm, prospective, multicenter, observational study was chosen as the study design. Parents who contacted an osteopathic practice with any of the following 5 health disturbances were invited to include their baby into the study: idiopathic infant asymmetry (IA), deformational plagiocephaly (DP), feeding disorders (FD), excessive crying (EC), and sleep disorders (SD). Osteopaths performed osteopathic treatment as usual for these conditions, and the parents were asked to rate the perceived severity of symptoms on standardized forms including numerical rating scales (NRS 0–10). In DP, the head circumference of the child’s skull was measured with a craniometer, and the cranial vault index (CVAI) was calculated. Results: 230 osteopaths agreed to participate, 151 osteopaths returned parental ratings. 1,136 infants were treated 2.8 ± 1.1 times (mean ± SD). IA was the most prevalent disturbance (48%), followed by EC (18%), FD (15%), DP (14%), and SD (4%). In IA, perceived asymmetry as rated on the NRS improved from 6.1 to 1.1, a mean improvement of 82%. In DP, the CVAI improved from 8.0 to 4.0%, a mean improvement of 51%. FD improved by 77%, EC by 70% (from 7.7 to 2.3 on the NRS) and SD by 56%. Adverse reactions with a timely association with osteopathic treatments were reported in 3.5% of all treatments, probably reflecting typical day-to-day variations in symptoms. In a total of 3,212 treatments, there was not a single serious adverse reaction affecting infant health. Conclusions: This is one of the largest studies worldwide to date on the osteopathic treatment of infants. Osteopathic treatment was associated with major positive changes in the severity of perceived health complaints as assessed by parents, which in most cases were resolved as a matter of concern, and was proved to be a safe treatment modality among a large number of therapists. Based on these results, confirmatory intervention studies can and should be planned and conducted.
Effects of Diet after Early Breast Cancer Treatment: A Systematic Review and Meta-Analysis of Clinical Trials
Authors: Träsel Henrique de Araújo Vianna , Falcetta Frederico Soares , de Almeida Fernando Kude , Falcetta Mariana Rangel Ribeiro , Ribeiro Rodrigo Antonini , Rosa Daniela Dornelles
Published: March 2021

Purpose: Randomized clinical trials (RCT) are inconclusive regarding the role of dietary interventions in anthropometric measurements and survival in breast cancer patients. Our aim was to conduct a systematic review and meta-analysis to assess the effects of diet on these outcomes in women treated for early-stage breast cancer. Methods: Embase, MEDLINE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched for RCT comparing dietary interventions (individualized dietary counseling, prescription of a specific diet, or others) with usual care in women that were treated for early breast cancer. Primary outcomes were overall survival (OS) and disease-free survival (DFS); secondary outcome was a change in body mass index (BMI). Results: We found 12 RCT eligible for analysis, 7 of which were included in the quantitative analysis. Two studies reported OS and DFS and 6 reported BMI data. The hazard ratio (HR) for OS and DFS was 0.91 (95% confidence interval [CI] 0.77–1.07, p = 0.25) and 0.92 (95% CI 0.79–1.08, p = 0.31) for the intervention and control groups, respectively. Intervention was associated with BMI reduction in subjects who received a specific diet instead of counseling or other types of intervention (–0.67; 95% CI –1.14 to –0.21). Conclusions: Despite increasing survival among breast cancer patients due to better oncological treatments, there is still a lack of prospective data regarding the effects of dietary interventions in this population. We found positive association between prescription of specific diets in terms of anthropometric measures; there were no differences in OS or DFS.
A Simple Surgical Technique for Pediatric Sinus Pericranii: Intraoperative Manual Compression of a Major Shunting Point
Authors: Fujimoto Yuki , Ishibashi Ryota , Maki Yoshinori , Kitagawa Masashi , Kinosada Masanori , Kurosaki Yoshitaka , Ikeda Hiroyuki , Chin Masaki
Published: March 2021

Introduction: Sinus pericranii is a vascular anomaly with extra- and intracranial venous connections. Sinus pericranii is categorized into 2 groups according to its contribution to the normal venous circulation. The accessory type sinus pericranii, which does not contribute to the normal major venous circulation, can be managed. Despite several proposed operative maneuvers, a standardized technique is yet to be established to control intraoperative bleeding. Case Presentation: A 2-week-old neonate underwent examination of a subcutaneous mass in the parieto-occipital region. The subcutaneous mass had a major venous connection to the superior sagittal sinus on ultrasonography. The subcutaneous mass was partially thrombolized on magnetic resonance imaging and was minimally enhanced on computed tomography venography. The subcutaneous mass seemed not to contribute to the normal venous circulation. Surgical removal of the subcutaneous mass was performed due to its increased size at the age of 1 year and 3 months. While subcutaneous mass was detached from the scalp, the major venous connection was manually compressed, and minor venous connections were easily detected. The intraoperative bleeding was controllable. The pathological diagnosis was sinus pericranii. The patient is now followed up in the outpatient clinic. No recurrence was seen 18 months after the surgery. Discussion/Conclusion: Intraoperative hemostasis is essential while sinus pericranii is detached from the cranium. Hemostatic agents such as bone wax or absorbable gelatin and heat coagulation seem to be useful. However, complicative hemorrhage concerning to the preceded technique has been also reported. As seen in our case, to detect minor shunting points between the sinus pericranii and the intracranial veins, the major venous connection was manually compressed. Intraoperative manual compression of a major venous connection of sinus pericranii can be an option to manage intraoperative bleeding.
P-Null Phenotype Due to a Rare Frame-Shift Mutation and with Allo-Anti-PP1Pk Causing a Severe Hemolytic Transfusion Reaction: A Case Report with Clinical Management
Authors: Kanani Ashish N. , Senjaliya Snehal B. , Rajapara Manisha M. , Aeschlimann Judith , Westhoff Connie M. , Joshi Sanmukh R.
Published: March 2021

Introduction:The identification of alloantibodies to high-frequency antigens (HFA) and subsequent transfusion management can be challenging and often poses a problem in finding the compatible blood for transfusion. The aim of this study was to investigate the specificity of the antibody to the HFA causing a hemolytic transfusion reaction (HTR) and procure the compatible blood unit for future transfusion. Case presentation:A 4-year-old female met with a head injury that led to intracranial bleeding and surgical intervention was required to remove blood clots. In the face of anemia, blood transfusion was planned. The pretransfusion tests on her blood sample revealed the presence of a pan-reactive alloantibody with hemolytic properties. She was transfused with 10 mL of the least incompatible red blood cells (RBCs) to which she reacted with signs of clinical hemolysis, i.e., chill, rigor, fever, and hemoglobinuria, on 3 different occasions. Despite her anemia, she was managed by medical intervention only. Her antibody reacted with all RBCs tested, except autologous and P-null (p phenotype) cells. Her RBCs did not react with anti-PP1Pk, which corroborated her phenotype as P-null. The genomic study revealed she was hemi- or homozygous or for a deletion of 26-bp in A4GALTexon 3, previously reported as causing the P-null phenotype and designated A4GALT*01N.019.Conclusion:This report documents a rare case of the P-null phenotype with an alloanti-PP1Pk causing a severe HTR to transfusion of the trial dose of the least incompatible blood. The case is the first example of this specific A4GALTmutation found in India.