bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalized Medicine for the Management of RDS in Preterm Neonates
Authors: De Luca Daniele , Autilio Chiara , Pezza Lucilla , Shankar-Aguilera Shivani , Tingay David G. , Carnielli Virgilio P.
Published: March 2021

Continuous positive airway pressure and surfactant represent the first- and second-line treatment for respiratory distress syndrome in preterm neonates, as European and American guidelines, since 2013 and 2014, respectively, started to recommend surfactant replacement only when continuous positive airway pressure fails. These recommendations, however, are not personalized to the individual physiopathology. Simple clinical algorithms may have improved the diffusion of neonatal care, but complex medical issues can hardly be addressed with simple solutions. The treatment of respiratory distress syndrome is a complex matter and can be only optimized with personalization. We performed a review of tools to individualize the management of respiratory distress syndrome based on physiopathology and actual patients’ need, according to precision medicine principles. Advanced oxygenation metrics, lung ultrasound, electrical impedance tomography, and both quantitative and qualitative surfactant assays were examined. When these techniques were investigated with diagnostic accuracy studies, reliability measures have been meta-analysed. Amongst all these tools, quantitative lung ultrasound seems the more developed for the widespread use and has a higher diagnostic accuracy (meta-analytical AUC = 0.952 [95% CI: 0.951–0.953]). Surfactant adsorption (AUC = 0.840 [95% CI: 0.824–0.856]) and stable microbubble test (AUC = 0.800 [95% CI: 0.788–0.812]) also have good reliability, but need further industrial development. We advocate for a more accurate characterization and a personalized approach of respiratory distress syndrome. With the above-described currently available tools, it should be possible to personalize the treatment of respiratory distress syndrome according to physiopathol­ogy.
Dalteparin in Newborn Thrombosis, Time for a New Starting Dose
Authors: Steenman Frouwke , Vijlbrief Daniel C. , Huisman Albert , Bierings Marc
Published: March 2021

Background: Neonatal thrombosis is a frequently encountered complication in a neonatal intensive care unit. Dalteparin can be used to treat thrombosis in newborn infants. Objectives: In this study, we evaluate the current recommended starting dose of 129 ± 43 U/kg/24 h, hypothesizing that this dose is too low to reach therapeutic anti-Xa levels. Methods: From 2008 until 2017, all infants treated with dalteparin in the University Medical Centre Utrecht were included in this study. In this retrospective cohort study, the correlation between dose and anti-Xa level was observed. Results: Sixty-six infants were included. The most common thrombus types were catheter-related (29 patients, 44%) and venous sinus thrombosis (28 patients, 43%). The mean dalteparin dose needed for the first adequate anti-Xa level (0.5–1.0 IU/mL) was 297.6 U/kg/12 h. Two infants developed a first bleeding episode under dalteparin therapy; they both had anti-Xa levels in the therapeutic range. Conclusion: The increase of the starting dose of dalteparin will lead to earlier therapeutic levels of anti-Xa in the studied population and appears to be safe. However, this needs to be evaluated in further study.
Neonatal Jaundice in Preterm Infants with Bilirubin Encephalopathy
Authors: Okumura Akihisa , Ichimura Shintaro , Hayakawa Masahiro , Arai Hiroshi , Maruo Yoshihiro , Kusaka Takashi , Kunikata Tetsuya , Kumada Satoko , Morioka Ichiro
Published: March 2021

Introduction: The aim of this study is to clarify bilirubin parameters and its treatment in preterm infants with bilirubin encephalopathy (pBE). Methods: We asked the responders to an earlier nationwide Japanese survey on pBE to provide additional information. pBE was diagnosed based on the criteria used in the nationwide survey. We collected data on serum total bilirubin (TB), direct bilirubin (DB), albumin, and unbound bilirubin (UB) levels during the first 8 weeks of life, and on phototherapy and exchange transfusion treatments. Results: We obtained clinical data from 75 patients with pBE from 58 hospitals (response rate of 59%), who were born between 2002 and 2016. The average peak TB level was 12.6 mg/dL (215 μmol/L), and the average age at peak attainment was 19.7 days after birth. Albumin level was <2.5 g/dL in 44 patients, and the peak DB level was ≥2 mg/dL (34.2 μmol/L) in 20 patients. The average peak bilirubin/albumin (B/A) (mg/g) ratio was 3.8 (molar ratio of 0.475), and the average age at peak attainment was 18.6 days. The average peak UB level was 0.67 μg/dL (11.5 nmol/L). The median duration of phototherapy was 6 days, and the median day of the last session was 12. The peak TB level occurred after the last day of phototherapy in 30 of the 61 patients available for comparison. Conclusions: Most patients with pBE lacked marked elevations in serum TB levels and the B/A ratio, the peaks of which were sometimes delayed to >4 weeks after birth.
Can Deep Brain Stimulation Withdrawal Syndromes Be Avoided by Removing Infected Implanted Pulse Generator and Cables with Contralateral Replacement in the Same Session?
Authors: Helmers Ann-Kristin , Kubelt Carolin , Paschen Steffen , Lübbing Isabel , Cohrs Gesa , Synowitz Michael
Published: March 2021

Objective: Infections are feared complications following deep brain stimulation in 1.9 to 17.6% of cases. These infections can necessitate the removal of implants, which carries the risk of life-threatening withdrawal syndromes, especially in patients suffering from Parkinson’s disease. In this report, we describe our procedure of removing an infected implanted pulse generator (IPG) and cables with contralateral replacement in the same session. Methods: We retrospectively analysed all patients with transpositions of an IPG and cables between 2017 and 2020 in a single-centre, university hospital setting. Medical records of all patients undergoing this particular surgical procedure were systematically reviewed. The shortest follow-up time was 12 months. Results: Between 2017 and 2020, we had 6 patients with a high risk of withdrawal syndrome in whom an infected IPG with cables was removed and replaced on the opposite side in the same session. There were postoperative complications in 2 patients: in one, the generator had to be re-affixed, and in the second, a skin transplant was required over one electrode because of skin necrosis. No case of invasive infection was seen, and the stimulation therapy was not interrupted. Conclusion: One-session removal of an IPG and cables with contralateral replacement seems to be an effective therapy for patients at high risk of withdrawal syndrome.
Effects of Obesity on Airway and Systemic Inflammation in Asthmatic Children
Authors: Vezir Emine , Civelek Ersoy , Dibek Misirlioglu Emine , Toyran Muge , Capanoglu Murat , Karakus Esra , Kahraman Tamer , Ozguner Meltem , Demirel Fatma , Gursel Ihsan , Kocabas Can Naci
Published: March 2021

Background: Obese asthma is a complex syndrome with certain phenotypes that differ in children and adults. There is no clear evidence regarding the presence of additive or synergistic pathological interaction between obesity and asthma in children. Objectives: Our aim was to demonstrate the interaction of obesity and asthma in children in terms of airway and systemic inflammation by a controlled observational study. Methods: Four groups were formed: asthma obese (AO), asthma nonobese (ANO), non-AO (NAO), nonasthma nonobese (NANO). Spirometry test, fractional exhaled nitric oxide (FeNO) test, skin prick test, serum inflammatory biomarkers (C-reactive protein, C3, C4, adiponectin, leptin, resistin, periostin, YKL-40, Type 1, and Type 2 cytokines) were conducted and evaluated in all participants. Sputum inflammatory cells (sputum eosinophils and neutrophils) were evaluated in patients who could produce induced sputum and obesity-asthma interactions were determined. Results: A total of 153 participants aged 6–18 years were included in the study, including the AO group (n = 46), the ANO group (n = 45), the NAO group (n = 30), and the NANO group (n = 32). IL-4 (p < 0.001), IL-5 (p < 0.001), IL-13 (p < 0.001), resistin (p < 0.001), and YKL-40 (p < 0.001) levels were higher in patients with asthma independent of obesity. The lowest adiponectin level was found in the AO group and obesity-asthma interaction was detected (p < 0.001). Sputum eosinophilia (p < 0.01), sputum neutrophilia (p < 0.01), and FeNO levels (p = 0.07) were higher in asthmatic patients independent of obesity. In the group with paucigranulocytic inflammation, resistin and YKL-40 levels were significantly lower than in the group without paucigranulocytic inflammation (p < 0.01). Conclusion: No interaction was found between obesity and asthma in terms of airway inflammation. Interaction between obesity and asthma was shown in terms of adiponectin level and resistin/adiponectin and leptin/adiponectin ratios. It was found that serum YKL-40 and resistin levels could be associated with airway inflammation.
Drip-and-Ship Model for Thrombectomy in Stroke Patients with Large-Vessel Occlusion
Authors: Huang Zhichao , Zhai Guojie , You Shoujiang , Ou Zhijie , Mao Xueyu , Cao Yongjun , Xiao Guodong , Liu Chun-Feng
Published: March 2021

Background: Previous studies have demonstrated the efficacy of the “drip-and-ship” model in acute ischemic stroke (AIS) patients treated with intravenous (IV) thrombolysis. We investigated and report the outcomes of the safety and efficacy of the “drip-and-ship” model in AIS patients with acute large-vessel occlusion (LVO) in the anterior circulation who underwent endovascular treatment. Methods: A total of 92 AIS patients with LVO who underwent endovascular treatment enrolled from April 2017 to July 2018 at a single academic comprehensive stroke center (CSC) were included. Patients were divided into 2 groups: a front-door group (directly admitted to the CSC) and a drip-and-ship group (transferred to the CSC from other hospital). Logistic regression model was used to evaluate the functional outcome, mortality, and symptomatic intracranial hemorrhage (sICH) at 90 days. Results: After adjusting for age, gender, occlusion site, National Institutes of Health Stroke Scale (NIHSS) score, and other potential covariates, we did not see difference in modified Rankin Scale (mRS) score between the 2 groups at 90 days. The rate of excellent functional outcome (defined as mRS 0–1) in the drip-and-ship group is lower than the front-door group (p = 0.017); however, functional outcomes (defined as mRS 0–2) have no difference (p = 0.117). There was no significant difference in sICH (p = 0.909) and mortality (p = 0.319) between the 2 groups. Conclusions: The “drip-and-ship” model has the potential to be a feasible model for patients with LVO in the anterior circulation to undergo endovascular treatment. Further large-scale prospective studies are warranted to confirm these findings.
Comprehensive Analysis of microRNA Profiles in Organoids Derived from Human Colorectal Adenoma and Cancer
Authors: Nagai Hiroshi , Kuroha Masatake , Handa Tomoyuki , Karasawa Hideaki , Ohnuma Shinobu , Naito Takeo , Moroi Rintaro , Kanazawa Yoshitake , Shiga Hisashi , Hamada Shin , Kakuta Yoichi , Naitoh Takeshi , Kinouchi Yoshitaka , Shimosegawa Tooru , Masamune Atsushi
Published: March 2021

Introduction: Exosomes are membrane-enclosed nanovesicles, which are increasingly being recognized as important cell communication components for their role in transmitting microRNAs (miRNAs). No previous study has addressed the exosomal miRNA profile in colorectal adenomas (CRAs) because the long-term culture of CRA is challenging. This study aimed to identify the miRNA signature in organoid exosomes derived from human CRA and colorectal cancer (CRC) samples. Methods: Organoid cultures were developed from resected colorectal tissues of patients with CRA or CRC undergoing surgery or endoscopic mucosal resection. Exosomes were prepared from the conditioned medium of the organoids. miRNAs were prepared from the exosomes and their source organoids. The miRNA expression profiles were compared using microarray analysis. The impact of alteration of miRNA expression on cell proliferation was examined using miRNA mimics or inhibitors in HT-29 human CRC cells. Results: We established 6 organoid lines from CRC and 8 organoid lines from CRA. Exosomal miRNA signatures were different between the organoids derived from CRA and CRC. Both exosomal and cellular miR-1246 expressions were upregulated in CRC-derived organoids compared to their expression in CRA-derived organoids. Alteration of miR-1246 expression by the miR-1246 mimic or inhibitor increased or decreased cell proliferation in HT-29 cells, respectively. Conclusions: We report for the first time the miRNA profiles of exosomes in CRA- and CRC-derived organoids. The upregulation of miR-1246 might play a role in increased cell proliferation in the process of CRA-carcinoma transition.
Triple Therapy with Tamsulosin, Dutasteride, and Imidafenacin for Benign Prostatic Hyperplasia in Patients with Overactive Bladder Symptoms Refractory to Tamsulosin: Subgroup Analyses of the DIrecT Study
Authors: Yamanishi Tomonori , Asakura Hirotaka , Seki Narihito , Tokunaga Shoji
Published: March 2021

Aim: To verify if the efficacy of the triple therapy with tamsulosin, dutasteride, and imidafenacin (TDI) is influenced by any background characteristics in patients with overactive bladder (OAB). Methods: A subanalysis of data from the DIrecT study was conducted. Superiority of TDI over tamsulosin and dutasteride in terms of efficacy based on the Overactive Bladder Symptom Score (OABSS), total International Prostate Symptom Score (IPSS), IPSS quality of life index, and postvoid residual (PVR) was evaluated in binary subgroups. Results: In the treatment groups, there was a significant interaction of total OABSS with testosterone level (≥4.8 vs. <4.8 ng/mL, p = 0.043) and PVR (≥20 vs. <20 mL, p = 0.018). For the total IPSS, no significant interaction was found except for the IPSS QOL index. For the IPSS QOL index, a significant interaction was found with testosterone level (≥4.8 vs. <4.8 ng/mL, p < 0.0001) as well as with total IPSS and total OABSS. For the PVR, no significant interaction was found except with total OABSS. Conclusions: Triple therapy with TDI is suggested to be a therapeutic option for benign prostatic hyperplasia in patients with residual OAB symptoms refractory to tamsulosin and in patients with various background characteristics regardless of severity of OAB symptoms. Trial Registry No. UMIN 000011980.
Physical Function and Clinical Outcomes in Hemodialysis Patients: China Dialysis Outcomes and Practice Patterns Study
Authors: Niu Qingyu , Zhao Xinju , Gan Liangying , Liang Xinling , Ni Zhaohui , Chen Xiaonong , Chen Yuqing , Hou Fan Fan , Zuo Li
Published: March 2021

Background: Hemodialysis (HD) patients usually have impaired physical function compared with the general population. Self-reported physical function is a simple method to implement in daily dialysis care. This study aimed to examine the association of self-reported physical function with clinical outcomes of HD patients. Methods: The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective cohort study. Data on 1,427 HD patients in China DOPPS5 were analyzed. Self-reported physical function was characterized by 2 items of “moderate activities limited level” and “climbing stairs limited level.” Demographic data, comorbidities, hospitalization, and death records were collected from patients’ records. Associations between physical function and outcomes were analyzed using COX regression models. Results: Compared to “limited a lot” in moderate activities, “limited a little” and “not limited at all” groups were associated with lower all-cause mortality after adjusted for covariates (HR: 0.652, 95% CI: 0.435–0.977, and HR: 0.472, 95% CI: 0.241–0.927, respectively). And, not limited in moderate activities was associated with lower risk of hospitalization than the “limited a lot” group after adjusted for covariates (HR: 0.747, 95% CI: 0.570–0.978). Meanwhile, compared to “limited a lot” in climbing stairs, “limited a little” and “not limited at all” groups were associated with lower all-cause mortality (HR: 0.574, 95% CI: 0.380–0.865 and HR: 0.472, 95% CI: 0.293–0.762, respectively) but not hospitalization after fully adjusted. Conclusion: Higher limited levels in self-reported physical function were associated with higher risk of all-cause mortality and hospitalization in HD patients.
Leaks after Left Atrial Appendage Closure: Ignored or Neglected?
Authors: Jang Sun-Joo , Wong S. Chiu , Mosadegh Bobak
Published: March 2021

Left atrial appendage (LAA) closure has recently been approved as an alternative management for stroke prevention in patients with chronic atrial fibrillation who have difficulties with long-term oral anticoagulation. The various shapes and sizes of LAA and orientation of the atrial ostium may contribute to the incomplete LAA closure from circular design devices and orientation of the non-steerable delivery catheter. Incomplete closure of LAA leads to a high-velocity blood flow through the peri-device gap, resulting in peri-device leak (PDL). Residual leaks are frequently diagnosed after LAA closure procedures, regardless of closure methods. There is a controversy in the clinical significance of the leaks, particularly about its association with thromboembolic events. PDL <5 mm was not associated with any increase of risk for thromboembolism. Current literatures with small study population have not been sufficient to clarify the role of the leaks after LAA closure. Nevertheless, management of severe leaks has been a challenging concern for cardiologists. Leaks after epicardial LAA closures are at the neck of the incompletely closed LAA and have shown to increase the risk of thromboembolism. Percutaneous closure of the leaks after LAA closure has been attempted with good safety and success, but long-term safety and efficacy remains unclear. Further large long-term studies which aim to assess the role of leaks or PDLs in predicting thromboembolic events and management strategies are warranted.
Serum Individual Nonesterified Fatty Acids and Risk of Heart Failure in Older Adults
Authors: Djousse Luc , Biggs Mary L. , Matthan Nirupa R. , Ix Joachim H. , Fitzpatrick Annette L. , King Irena , Lemaitre Rozenn N. , McKnight Barbara , Kizer Jorge R. , Lichtenstein Alice H. , Mukamal Kenneth J. , Siscovick David S.
Published: March 2021

Background: Heart failure (HF) is highly prevalent among older adults and is associated with high costs. Although serum total nonesterified fatty acids (NEFAs) have been positively associated with HF risk, the contribution of each individual NEFA to HF risk has not been examined. Objective: The aim of this study was to examine the association of individual fasting NEFAs with HF risk in older adults. Methods: In this prospective cohort study of older adults, we measured 35 individual NEFAs in 2,140 participants of the Cardiovascular Health Study using gas chromatography. HF was ascertained using review of medical records by an endpoint committee. Results: The mean age was 77.7 ± 4.4 years, and 38.8% were male. During a median follow-up of 9.7 (maximum 19.0) years, 655 new cases of HF occurred. In a multivariable Cox regression model controlling for demographic and anthropometric variables, field center, education, serum albumin, glomerular filtration rate, physical activity, alcohol consumption, smoking, hormone replacement therapy, unintentional weight loss, and all other measured NEFAs, we observed inverse associations (HR [95% CI] per standard deviation) of nonesterified pentadecanoic (15:0) (0.73 [0.57–0.94]), γ-linolenic acid (GLA) (0.87 [0.75–1.00]), and docosahexaenoic acid (DHA) (0.73 [0.61–0.88]) acids with HF, and positive associations of nonesterified stearic (18:0) (1.30 [1.04–1.63]) and nervonic (24:1n-9) (1.17 [1.06–1.29]) acids with HF. Conclusion: Our data are consistent with a higher risk of HF with nonesterified stearic and nervonic acids and a lower risk with nonesterified 15:0, GLA, and DHA in older adults. If confirmed in other studies, specific NEFAs may provide new targets for HF prevention.
Two Cases of Possible Familial Chronic Myeloid Leukemia in a Family with Extensive History of Cancer
Authors: Aitken Marisa J.L. , Benton Christopher B. , Issa Ghayas C. , Sasaki Koji , Yilmaz Musa , Short Nicholas J.
Published: March 2021

CML is defined by the presence of an oncogenic fusion protein caused by a reciprocal translocation between chromosomes 9q and 22q. While our molecular understanding of CML pathogenesis has revolutionized drug development for this disease, we have yet to identify many predisposing factors for CML. Familial occurrence of CML has been rarely reported. Here, we describe 2 cases of CML in a 24-year-old woman and in her 73-year-old maternal great aunt. We describe genetic variants in these patients and report on their environmental exposures that may have contributed to CML pathogenesis. The possible familial association of these 2 cases of CML warrants further investigation into more definitive etiologies of this disease.
Community- and Hospital-Acquired Acute Kidney Injury in COVID-19: Different Phenotypes and Dismal Prognosis
Authors: Martínez-Rueda Armando J. , Álvarez Rigoberto D. , Méndez-Pérez R. Angélica , Fernández-Camargo Dheni A. , Gaytan-Arocha Jorge E. , Berman-Parks Nathan , Flores-Camargo Areli , Comunidad-Bonilla Roque A. , Mejia-Vilet Juan M. , Arvizu-Hernandez Mauricio , Ramirez-Sandoval Juan C. , Correa-Rotter Ricardo , Vega-Vega Olynka
Published: March 2021

Introduction: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). It is unknown if hospital-acquired AKI (HA-AKI) and community-acquired AKI (CA-AKI) convey a distinct prognosis. Methods: The study aim was to evaluate the incidence and risk factors associated with both CA-AKI and HA-AKI. Consecutive patients hospitalized at a reference center for COVID-19 were included in this prospective cohort study. Results: We registered 349 (30%) AKI episodes in 1,170 hospitalized patients, 224 (19%) corresponded to CA-AKI, and 125 (11%) to HA-AKI. Compared to patients with HA-AKI, subjects with CA-AKI were older (61 years [IQR 49–70] vs. 50 years [IQR 43–61]), had more comorbidities (hypertension [44 vs. 26%], CKD [10 vs. 3%]), higher Charlson Comorbidity Index (2 points [IQR 1–4] vs. 1 point [IQR 0–2]), and presented to the emergency department with more severe disease. Mortality rates were not different between CA-AKI and HA-AKI (119 [53%] vs. 63 [50%], p = 0.66). In multivariate analysis, CA-AKI was strongly associated to a history of CKD (OR 4.17, 95% CI 1.53–11.3), hypertension (OR 1.55, 95% CI 1.01–2.36), Charlson Comorbidity Index (OR 1.16, 95% CI 1.02–1.32), and SOFA score (OR 2.19, 95% CI 1.87–2.57). HA-AKI was associated with the requirement for mechanical ventilation (OR 68.2, 95% CI 37.1–126), elevated troponin I (OR 1.95, 95% CI 1.01–3.83), and glucose levels at admission (OR 1.05, 95% CI 1.02–1.08). Discussion/Conclusions: CA-AKI and HA-AKI portend an adverse prognosis in CO­VID-19. Nevertheless, CA-AKI was associated with a higher comorbidity burden (including CKD and hypertension), while HA-AKI occurred in younger patients by the time severe multiorgan disease developed.
Perioperative Predictive Markers for Recurrence of Esophageal Cancer after Esophagectomy
Authors: Fujiwara Yoshinori , Higashida Masaharu , Kubota Hisako , Okamoto Yuko , Mineta Shumei , Endo Shunji , Ueno Tomio
Published: March 2021

Introduction: We studied whether perioperative nutritional, immunological factors or postoperative inflammatory responses predicted esophageal cancer (EC) progression and prognosis in patients who received esophagectomies. Methods: We evaluated preoperative prognostic nutritional index (PNI), BMI, neutrophil-to-lymphocyte ratio (NLR), intraoperative blood loss, postoperative C-reactive protein (CRP) max, recurrence-free survival (RFS), and overall survival (OS) in 111 patients with pStage I–IV squamous cell EC who received esophagectomies. Optimal cutoff values for each continuous parameter were determined by receiver operating characteristic curves and Youden indices. Univariate and multivariate Cox analyses were used to derive independent prognostic factors. Propensity score matching using inverse probability of treatment weighting was used in groups divided by Youden indices, as appropriate. Results: Cutoff values of continuous variables were NLR: 2.27, PNI: 44.2, blood loss: 159 mL, and CRPmax: 21.7 mg/dL. In multivariate analyses, PNI, CRPmax, and intraoperative blood loss were independent prognostic factors for OS and RFS. Among patients with stage II–IV disease, low PNI was associated with shorter RFS. Postoperative respiratory complications were associated with both higher CRP and shorter RFS. Discussion/Conclusions: Low preoperative PNI and high postoperative inflammatory response were associated with postoperative EC progression after esophagectomy. Preoperative nutritional interventions or suppression of postoperative inflammatory response, including respiratory complications, may improve patient prognosis.
The Association of the Brief Dementia Risk Index and Incident Dementia among Finnish 70-Year-Olds: A 5-Year Follow-Up Study
Authors: Vire Jenni , Salminen Marika , Viikari Paula , Vahlberg Tero , Arve Seija , Viitanen Matti , Viikari Laura
Published: March 2021

Background: An accurate identification of older individuals at increased risk of developing dementia is very important. Various dementia risk prediction models have been developed, but not all models are applicable among older population. Objectives: To examine the association of the Brief Dementia Risk Index (BDRI) and incidence of dementia among community-dwelling Finnish older adults. Methods: Participants were community-dwelling nondemented 70-year-olds examined in 2011 (n = 943). Cox regression model with death as a competing risk was used to analyze the association of BDRI and incident dementia (ICD-10 codes F00-03 and G30) during the 5-year follow-up (n = 883). Results: The rate of dementia incidence was 4.9% during the follow-up. Having at least moderate risk according to BDRI significantly predicted incident dementia (hazard ratio 3.18, 95% confidence interval: 1.71–5.92, p < 0.001), also after adjustment with education level (2.93, 1.52–5.64, p = 0.001). No interaction between gender and BDRI was found. Conclusion: BDRI could be an applicable tool for identification of older individuals at increased risk of developing dementia in clinical settings.
Cytologic Features of Lipogranulomatous Reaction in an Axillary Sentinel Lymph Node
Authors: Jimenez-Heffernan Jose Antonio , Valdivia-Mazeyra Mariel , Muñoz-Hernández Patricia , López-Elzaurdia Consuelo
Published: March 2021

Introduction: Multinucleated giant cells (MGC) are a rare finding when evaluating axillary sentinel lymph nodes. Some are described as foreign body-type MGC accompanied by foamy macrophages. They have been rarely reported in nodes from patients in which a previous breast biopsy was performed. The tissue damage induced by biopsy results in secondary changes including fat necrosis and hemorrhage that can migrate to axillary nodes. In this report, we illustrate a lipogranulomatous reaction in cytologic samples obtained during a sentinel lymph node examination of a woman previously biopsied because of breast carcinoma. We have found no previous cytologic descriptions and consider it an interesting finding that should be known to avoid diagnostic misinterpretations. Case: A 51-year-old woman underwent mastectomy of the right breast with a sentinel lymph node biopsy at our medical center. One month before, a control mammography revealed suspicious microcalcifications and a vacuum-assisted breast biopsy resulted in a diagnosis of high-grade intraductal carcinoma with comedonecrosis. Surgery with a sentinel lymph node biopsy was performed. The sentinel node was processed as an intraoperative consultation. Frozen sections and air-dried Diff-Quik stained samples were obtained. They showed abundant lymphocytes with MGC and tumoral cells. MGC showed ample cytoplasm with evident vacuoles of variable size. Occasional hemosiderin-laden macrophages were also present. The complete histologic analysis and immunohistochemical studies revealed no malignant cells. Histologic analysis showed, in subcapsular location, occasional MGC phagocyting lipid droplets. Hemosiderin-laden macrophages were a common finding. Conclusion: Lipogranulomas may appear at axillary sentinel lymph nodes because of fat necrosis induced by previous breast biopsy. The most important consideration is not confounding MGC with epithelial cell clusters. This can occur with not well-processed samples, especially if unmounted.
Respiratory Muscle Weakness as a Risk Factor for Pneumonia in Older People
Authors: Okazaki Tatsuma , Suzukamo Yoshimi , Miyatake Midori , Komatsu Riyo , Yaekashiwa Masahiro , Nihei Mayumi , Izumi Shinichi , Ebihara Takae
Published: March 2021

Introduction: The respiratory muscle strength regulates the effectiveness of coughing, which clears the airways and protects people from pneumonia. Sarcopenia is an aging-related loss of muscle mass and function, the worsening of which is associated with malnutrition. The loss of respiratory and swallowing muscle strength occurs with aging, but its effect on pneumonia is unclear. This study aimed to determine the risks of respiratory muscle weakness on the onset and relapse of pneumonia in older people in conjunction with other muscle-related factors such as malnutrition. Methods: We conducted a longitudinal study with 47 pneumonia inpatients and 35 non-pneumonia controls aged 70 years and older. We evaluated the strength of respiratory and swallowing muscles, muscle mass, and malnutrition (assessed by serum albumin levels and somatic fat) during admission and confirmed pneumonia relapse within 6 months. The maximal inspiratory and expiratory pressures determined the respiratory muscle strength. Swallowing muscle strength was evaluated by tongue pressure. Bioelectrical impedance analysis was used to evaluate the muscle and fat mass. Results: The respiratory muscle strength, body trunk muscle mass, serum albumin level, somatic fat mass, and tongue pressure were significantly lower in pneumonia patients than in controls. Risk factors for the onset of pneumonia were low inspiratory respiratory muscle strength (odds ratio [OR], 6.85; 95% confidence interval [CI], 1.56–30.11), low body trunk muscle mass divided by height2 (OR, 6.86; 95% CI, 1.49–31.65), and low serum albumin level (OR, 5.46; 95% CI, 1.51–19.79). For the relapse of pneumonia, low somatic fat mass divided by height2 was a risk factor (OR, 20.10; 95% CI, 2.10–192.42). Discussion/Conclusions: Respiratory muscle weakness, lower body trunk muscle mass, and malnutrition were risk factors for the onset of pneumonia in older people. For the relapse of pneumonia, malnutrition was a risk factor.
Adolescent Gynecomastia due to Minimal Androgen Resistance Syndrome: A Case Report and Literature Review
Authors: Fiorini Aureliano , Sepich Margherita , Pontrelli Margherita , Sangriso Giorgio , Cosci o Di Coscio Mirna , Lauletta Marcella , Baldinotti Fulvia , Peroni Diego , Ambrosio Maria Rosaria , Bertelloni Silvano
Published: March 2021

A 14-year-old boy with a 46,XY karyotype and persistent breast-3-stage gynecomastia is reported. The reproductive axis was investigated by standard laboratory methods and the androgen receptor (AR) gene was sequenced. Also, a literature review of phenotypes associated with the AR genetic variant p.Pro392Ser was performed. The boy presented with height in the upper normal range (+1.9 SDS) and normal body mass index (−0,3 SDS); pubertal development was PH5/G4 (mean testicular volume 15 mL; 0 SDS). Laboratory findings were normal for age and sex, except aromatization index (0.09; reference range 0.03–0.07). Analysis of the AR gene showed the single nucleotide variant c.1174C>T (p.Pro392Ser) in exon 1, leading to the diagnosis of minimal androgen insensitivity syndrome (AIS). This genetic variant is reported in other 8 patients with AIS and is associated with variable clinical phenotypes ranging from complete to partial and minimal AIS. To the best of our knowledge, this is the first adolescent in whom the p.Pro392Ser mutation is associated with isolated persistent gynecomastia. The underlying reason of phenotypic variability due to this AR mutation remains unknown. Persistent gynecomastia due to minimal AIS has been reported in few additional males with variable AR mutations. Since fertility troubles may occur in adult men with minimal AIS, early diagnosis can allow optimizing the clinical management.
Laparoscopic Repositioning of Gonads from the Labia Majora or Inguinal Canal into the Abdominal Cavity in Pediatric Complete Androgen Insensitivity Syndrome Patients with Inguinal Hernia
Authors: Lee Sung Ryul
Published: March 2021

Androgen insensitivity syndrome (AIS) is a congenital condition characterized by a 46,XY karyotype but with a female phenotype caused by mutations in the androgen receptor gene located on the X chromosome. In patients with complete AIS (CAIS), preservation of the gonad is recommended until puberty, and gonadectomy can be regarded subsequently. The location of the gonads should be considered, because positions in the labia majora or inguinal canals can cause discomfort. Here, the laparoscopic reposition of gonads into the abdominal cavity in pediatric patients with CAIS is reported. From 2013 to 2019, laparoscopic inguinal hernia repair was performed in 2,061 pediatric patients with inguinal hernias aged <10 years and with female external genitalia. Among them, 11 had CAIS. Gonads located in the labia majora or inguinal canal were repositioned into the abdominal cavity. The mean age was 18.9 months (range 1–110 months). The gonads were located in the inguinal canal in 7 patients, in the labia majora in 3, and in the abdominal cavity in 1. Laparoscopic repositioning of such gonads into the abdominal cavity is feasible in pediatric patients with an inguinal hernia and CAIS.
Intrachromosomal Amplification of Chromosome 21 in Childhood Acute Lymphoblastic Leukemia: Study of 3 Cases
Authors: Mroczkowska Aleksandra , Lejman Monika
Published: March 2021

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. The presence or absence of a characteristic genetic abnormality usually observed in childhood ALL plays a very important role in determining the prognosis and stratification for treatment. Intrachromosomal amplification of chromosome 21 (iAMP21) is an uncommon high-risk chromosomal abnormality than can occur only in 2% of childhood B-cell precursor lymphoblastic leukemia. Molecular genetic analysis and the fluorescence in situ hybridization (FISH) technique are the basic methods used to detect the presence of the most common genetic abnormalities, the presence or absence of which has an impact on the patient’s classification into the appropriate risk group. This work presents 3 BCP-ALL iAMP21-positive patients who were detected during routine genetic diagnostics using the FISH method and microarray test. iAMP21 is associated with a poor prognosis and high risk for relapse. Children with B-cell precursor lymphoblastic leukemia with this genetic entity are associated with a delayed treatment response. The FISH method and single-nucleotide polymorphism array provides a useful method to detect characteristic genetic changes.
Bronchoscopic Thermal Vapour Ablation for Localized Cancer Lesions of the Lung: A Clinical Feasibility Treat-and-Resect Study
Authors: Steinfort Daniel P. , Christie Michael , Antippa Phillip , Rangamuwa Kanishka , Padera Robert , Müller Michael Rolf , Irving Louis B. , Valipour Arschang
Published: March 2021

Background: Bronchoscopic thermal vapour ablation (BTVA) is an established and approved modality for minimally invasive lung volume reduction in severe emphysema. Preclinical data suggest potential for BTVA in minimally invasive ablation of lung cancer lesions. Objectives: The objective of this study is to establish the safety, feasibility, and ablative efficacy of BTVA for minimally invasive ablation of lung cancers. Methods: Single arm treat-and-resect clinical feasibility study of patients with biopsy-confirmed lung cancer. A novel BTVA for lung cancer (BTVA-C) system for minimally invasive treatment of peripheral pulmonary tumours was used to deliver 330 Cal thermal vapour energy via bronchoscopy to target lesion. Patients underwent planned lobectomy to complete oncologic care. Pre-surgical CT chest and post-resection histologic analysis were performed to evaluate ablative efficacy. Results: Six patients underwent BTVA-C, and 5 progressed to planned lobectomy. Median procedure duration was 12 min. No major procedure-related complications occurred. All 5 resected lesions were part-solid lung adenocarcinomas with median solid component size 1.32±0.36 cm. Large uniform ablation zones were seen in 4 patients where thermal dose exceeded 3 Cal/mL, with complete/near-complete necrosis of target lesions seen in 2 patients. Tumour positioned within ablation zones demonstrated necrosis in >99% of cross-sectional area examined. Conclusion: BTVA of lung tumours is feasible and well tolerated, with preliminary evidence suggesting high potential for effective ablation of tumours. Thermal injury is well demarcated, and uniform tissue necrosis is observed within ablation zones receiving sufficient thermal dose per volume of lung. Treatment of smaller volumes and ensuring adequate thermal dose may be important for ablative efficacy.
A COVID-19 Risk Reduction Assessment for a Health-Care Employee from an Ethnic Background: A Case Study in the United Kingdom
Authors: Chetty Laran
Published: March 2021

Concerns in the United Kingdom (UK) that Black, Asian and Minority Ethnic (BAME) populations have disproportionately higher rates of coronavirus disease 2019 (COVID-19) than white populations have led to ethnicity being identified as a risk factor within the latest guidance from Public Health England. The purpose of this case report was to determine whether the risk reduction assessment would aid the line manager support a BAME health-care employee who was concerned that his ethnicity put him at greater risk of contracting COVID-19. This report described the case, protocol, and outcome of undertaking a risk reduction assessment. It is concluded that the risk reduction assessment may assist line managers implement appropriate adjustments for BAME employees in order to alleviate their concerns and mitigate the risks of COVID-19.
Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer
Authors: Kang Hyo-Gyoung , Park Ji Eun , Lee Shin Yup , Choi Jin Eun , Do Sook Kyung , Hong Mi Jeong , Lee Jang Hyuck , Jeong Ji Yun , Do Young Woo , Lee Eung Bae , Shin Kyung Min , Lee Won Ki , Choi Sun Ha , Lee Yong Hoon , Seo Hye won , Yoo Seung Soo , Lee Jaehee , Cha Seung Ick , Kim Chang Ho , Cho Sukki , Jheon Sanghoon , Park Jae Yong
Published: March 2021

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
Tissue Sodium Concentration within White Matter Correlates with the Extent of Small Vessel Disease
Authors: Adlung Anne , Samartzi Melina , Schad Lothar R. , Neumaier-Probst Eva , Fatar Marc , A. Mohamed Sherif
Published: March 2021

Introduction: Sodium MRI (23Na MRI) derived biomarkers such as tissue sodium concentration (TSC) provide valuable information on cell function and brain tissue viability and has become a reliable tool for the assessment of brain tumors and ischemic stroke beyond pathoanatomical morphology. Patients with major stroke often suffer from different degrees of underlying white matter lesions (WMLs) attributed to chronic small vessel disease. This study aimed to evaluate the WM TSC in patients with an acute ischemic stroke and to correlate the TSC with the extent of small vessel disease. Furthermore, the reliability of relative TSC (rTSC) compared to absolute TSC in these patients was analyzed. Methodology: We prospectively examined 62 patients with acute ischemic stroke (73 ± 13 years) between November 2016 and August 2019 from which 18 patients were excluded and thus 44 patients were evaluated. A 3D 23Na MRI was acquired in addition to a T2-TIRM and a diffusion-weighted image. Coregistration and segmentation were performed with SPM 12 based on the T2-TIRM image. The extension of WM T2 hyperintense lesions in each patient was classified using the Fazekas scale of WMLs. The absolute TSC in the WM region was correlated to the Fazekas grades. The stroke region was manually segmented on the coregistered absolute diffusion coefficient image and absolute, and rTSC was calculated in the stroke region and compared to nonischemic WM region. Statistical significance was evaluated using the Student t-test. Results: For patients with Fazekas grade I (n = 25, age: 68.5 ± 15.1 years), mean TSC in WM was 55.57 ± 7.43 mM, and it was not statistically significant different from patients with Fazekas grade II (n = 7, age: 77.9 ± 6.4 years) with a mean TSC in WM of 53.9 ± 6.4 mM, p = 0.58. For patients with Fazekas grade III (n = 9, age: 81.4 ± 7.9 years), mean TSC in WM was 68.7 ± 10.5 mM, which is statistically significantly higher than the TSC in patients with Fazekas grade I and II (p < 0.001 and p = 0.05, respectively). There was a positive correlation between the TSC in WM and the Fazekas grade with r = 0.48 p < 0.001. The rTSC in the stroke region was statistically significant difference between low (0 and I) and high (2 and 3) Fazekas grades (p = 0.0353) whereas there was no statistically significant difference in absolute TSC in the stroke region between low (0 and I) and high (2 and 3) Fazekas grades. Conclusion: The significant difference in absolute TSC in WM in patients with severe small vessel disease; Fazekas grade 3 can lead to inaccuracies using rTSC quantification for evaluation of acute ischemic stroke using 23 Na MRI. The study, therefore, emphasizes the importance of absolute tissue sodium quantification.
Impact of Mediterranean Diet prior to Stroke on the Prognosis of Patients Undergoing Endovascular Treatment
Authors: García-Cabo Carmen , Castañón-Apilánez Maria , Benavente-Fernández Lorena , Jimenez Jose Maria , Arenillas Juan , Castellanos Mar , Rodrigo-Stevens Gabriela , Tejada-Meza Herbert , Pérez Cristina , Martínez-Zabaleta Maite , Rodriguez-Castro Emilio , Sánchez Joaquín , Julian-Villaverde Francisco , Pinedo Ana , Palacio Enrique , López-Cancio Elena ,   on behalf of the NORDICTUS investigators
Published: March 2021

Introduction: Mediterranean diet (MeDiet) has been associated with lower risk of stroke. Additionally, animal models suggested that some components of MeDiet are associated with better outcomes after ischemic stroke (IS). We aimed to evaluate the association between global adherence to the MeDiet and the consumption of particular components of the MeDiet with stroke outcomes. Material and Methods: Multicenter observational study of consecutive IS patients treated with endovascular therapy. Inclusion criteria were large anterior circulation vessel occlusion and pre-stroke modified Rankin scale (mRS) <2. Adherence to MeDiet prior to stroke was evaluated using MEDAS 14-item scale. We evaluated the total score and also individual components of the scale. Clinical, radiological, and prognostic variables were collected. Good functional prognosis was considered as mRS ≤2 and complete recanalization as thrombolysis in cerebral infarction 3. Results: From January 1 to October 30, 2018, 239 patients were included (mean age 71 years, 48% women, median baseline NIHSS 16). Median MEDAS scale was 8 points (7–10). Patients with a higher adherence to MeDiet had significantly lower total and LDL-cholesterol levels. Total adherence score was not associated with stroke outcomes. In multivariate analyses, consumption of olive oil as the principal source of fat was independently associated with good functional outcome at 3 months, OR 3.2 (1.1–10.1) and daily consumption of wine was independently associated with complete recanalization, OR 2.0 (1.1–3.8). Conclusions: Our study suggests that some components of MeDiet, such as olive oil and wine consumption, are related to better prognosis after stroke. More studies are needed to confirm these findings.