bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Utility of Galactose-Deficient Immunoglobulin A1 Immunostaining in the Differentiation of Lupus Nephritis and Immunoglobulin A Nephropathy
Authors: Bu Lihong , Ye Bo , Kouri Anne M. , Kim Youngki
Published: March 2021

Background: Renal biopsy plays an important role in the establishment of the diagnosis and the management of patients with lupus nephritis. Immunoglobulin A (IgA) nephropathy rarely has been reported in kidney biopsy of lupus patients. Lupus nephritis and IgA nephropathy can be readily diagnosed on renal biopsy when the classic patterns are present. However, atypical patterns can become a diagnostic challenge. Galactose-deficient IgA1 (Gd-IgA1) is a key element in the pathogenesis of primary IgA nephropathy. Glomerular Gd-IgA1 deposits, detected by immunofluorescent staining of KM-55 (a Gd-IgA1-specific monoclonal antibody), are consistently identified in the mesangium of IgA nephropathy but are significantly less or absent in lupus nephritis accompanied by significant IgA deposition. Case Presentation: Here we report the case of an 11-year-old girl who was recently diagnosed with systemic lupus erythematosus (SLE) and was found to have hematuria and proteinuria. Renal biopsy showed focal mesangial hypercellularity with IgA dominant, “full house” like pattern of mesangial deposition. The biopsy findings present a diagnostic dilemma with the differential diagnosis of IgA nephropathy versus lupus nephritis with atypical immunofluorescence, and IgA nephropathy is favored, in the absence of strong straining of C1q or C3, extraglomerular deposits, tissue antinuclear antibodies, and endothelial tubuloreticular inclusions. However, no detectable glomerular KM-55 staining was seen in the kidney biopsy. Conclusions: We demonstrate the unique diagnostic utility of immunostaining for KM-55 in a challenging kidney biopsy of an SLE patient with features suggestive of IgA nephropathy. The absence of KM-55 staining excludes IgA nephropathy, supporting a diagnosis of lupus nephritis with atypical immunofluorescence in this patient with SLE.
Nonscarring Alopecia and Hypopigmented Lesions May Be Unusual Signs of Secondary Syphilis
Authors: Ciupińska Magdalena , Skibińska Justyna , Sikora Mariusz , Blicharz Leszek , Kotowska Maja , Rudnicka Lidia
Published: March 2021

Noncicatricial patchy alopecia of the scalp and focal areas of skin hypopigmentation imply a diagnosis of alopecia areata and vitiligo. We present a case of a 22-year-old patient in whom these symptoms were associated with positive spirochete reactions, which allowed making a diagnosis of syphilitic alopecia coexisting with leukoderma syphiliticum. Skin lesions and hair loss resolved after the treatment with benzathine benzylpenicillin. Trichoscopy in syphilitic alopecia is nonspecific, but the absence of features typical for alopecia areata such as exclamation mark hairs may be important on an early stage of the clinical workup.
Validation of the Opioid Overdose Knowledge (OOKS) and Attitudes (OOAS) Scales in French, Spanish, and German Languages, among a Sample of Opioid Users
Authors: Laconi Stéphanie , Palma-Alvarez Raul Felipe , Stöver Heino , Padberg Christina , Jamin Daniela , Meroueh Fadi , Chappuy Mathieu , Roncero Carlos , Rolland Benjamin
Published: March 2021

Introduction: Improving the knowledge and attitudes of people facing an opioid overdose is one of the key prevention measures for reducing overdose occurrence and severity. In this respect, the Opioid Overdose Knowledge Scale (OOKS) and Opioid Overdose Attitudes Scale (OOAS) have been developed and validated in English to assess and improve knowledge and attitudes of opioid users and their families and care providers, in case of an overdose. Here, the OOKS and OOAS scales have been translated into French, Spanish, and German, and the different versions of the 2 scales have been assessed regarding their psychometric properties. Methods: The translation procedure of the scales was based on the international recommendations, including a back translation by a native English speaker. Subsequently, 80 (Spain: 29, France: 27, Germany: 24) former or current heroin users, aged from 20 to 61 years (M = 39.4 ± 9.23), completed the OOKS and OOAS versions of their native language, in test-retest, without specific between-assessment training. Internal consistency was assessed using Cronbach’s α, while test-retest reliability was assessed using intraclass correlation coefficient (ICC). The correlation between the OOKS and OOAS scores of a same language was assessed using Spearman’s (ρ) coefficient. Results: Internal consistency of the OOKS was found to be good to very good, with Cronbach’s α ranging from 0.62 to 0.87. Test-retest reliability was also very good, with ICCs ranging from 0.71 to 0.82. However, results were less reliable for the OOAS, as internal consistency was questionable to acceptable, with Cronbach’s α ranging from 0.12 to 0.63, while test-retest ICCs were very good for the French (0.91) and Spanish (0.99) versions and barely acceptable for the German version (0.41). No significant correlation was found between the OOKS and OOAS scores, irrespective of the version concerned. Conclusion: While satisfactory results were found for the 3 versions of the OOKS, results on the OOAS were relatively inconsistent, suggesting a possible gap between knowledge and attitudes on overdose among opioid users.
Novel Use of a Modified Triangular Prismatic Double-J Stent for 2- to 3-cm Renal Stones after One-Stage Retrograde Intrarenal Surgery
Authors: Wang Rui , Hu Yude , Xie Haijie , Xie Linguo , Yang Yu , Liu Chunyu
Published: March 2021

Objectives: To initially evaluate the outcomes of the modified triangular prismatic double-J (DJ) stent in the management of 2- to 3-cm renal stones after one-stage retrograde intrarenal surgery (RIRS). Methods: Patients with 2- to 3-cm renal stones who underwent one-stage RIRS with indwelling DJ stents were retrospectively evaluated. Eighty-eight patients who were placed the triangular prismatic DJ stents and 64 patients who received standard DJ stents were randomly included. The clinical characteristics and intraoperative and postoperative outcomes of the 2 groups were compared and analyzed. Results: The 2 groups had similar baseline characteristics. The urinary symptom score and pain score did not differ between groups (p > 0.05). The residual fragments of the 2 groups were similar 1 day after operation (p = 0.134). There was no significant difference in residual fragments in the lower calyx between groups at the time of stent removal (p = 0.834). The patients in the modified group had better spontaneous passage of residual fragments in the nonlower calyx than those in the standard group during the 2 weeks with the stents (p = 0.005). Fewer patients in the modified group had residual fragments (>4 mm) in the nonlower calyx (p = 0.026) and ureter (p = 0.010) than the patients with standard stents at the time of stent removal. Conclusion: The indwelling triangular prismatic DJ stent is a safe and efficient treatment method. Patients with these stents had better spontaneous residual fragment passage than those with the standard DJ stents.
Pareidolias and Creativity in Patients with Mental Disorders
Authors: Mavrogiorgou Paraskevi , Peitzmeier Nils , Enzi Björn , Flasbeck Vera , Juckel Georg
Published: March 2021

Objective: Pareidolias are ilusionary misjudgments and are seen as the result of deliberately or unconsciously caused misinterpretations by the human brain, which tends to complete diffuse and apparently incomplete perceptual images. The psychopathological value of pareidolia in the context of neuropsychiatric diseases has, however, been little researched so far. Methods: In this pilot study, a total of 25 patients (mean age 43.3 years, SD 16.2) with an affective disorder or schizophrenic disease (ICD-10: F3.X or F2.X) and 25 healthy volunteers (mean age 46.1 years, SD 15.4) were compared for sociodemographic factors and psychometric findings, as well as pareidolias and creativity. Results: We found that the patients identified significantly fewer pareidolias than healthy controls (p = 0.002) and that patients with schizophrenia, in particular, had a significantly lower hit rate (p = 0.005). Across the whole group, there were clear positive correlations between pareidolia and high creativity, as well as personality traits such as impulsiveness/spontaneity, extraversion, and conscientiousness. Conclusions: Unexpectedly, having less nosology-specific features than individual specific properties such as creativity and extraversion, and especially openness and verbal intelligence, in patients with affective disorder or schizophrenia promotes the recognition of pareidolia as a specific form of illusionary misperception.
Stronger Effect of Azilsartan on Reduction of Proteinuria Compared to Candesartan in Patients with CKD: A Randomized Crossover Trial
Authors: Suehiro Takaichi , Tsuruya Kazuhiko , Yoshida Hisako , Tsujikawa Hiroaki , Yamada Shunsuke , Tanaka Shigeru , Tsuchimoto Akihiro , Eriguchi Masahiro , Fujisaki Kiichiro , Torisu Kumiko , Nakano Toshiaki , Kitazono Takanari
Published: March 2021

Introduction: Angiotensin receptor blockers (ARBs) are preferably used in hypertensive patients with CKD. Azilsartan is a strong antihypertensive ARB, but its antiproteinuric effects are not well understood. We compared the antiproteinuric effect of azilsartan and candesartan in CKD patients in an open-label, randomized, crossover trial. Methods: A total of 111 patients were treated with 20 mg of azilsartan daily for 2 months as a run-in period. After the run-in period, patients were randomized into 2 arms and received either 20 mg of azilsartan or 8 mg of candesartan daily for 3 months in a crossover trial. The primary outcome was the percent change in urinary protein-to-Cr ratio (UPCR). Results: Ninety-five patients completed the trial. The mean age was 64.3 years. The estimated glomerular filtration rate (eGFR) and UPCR were 41.5 mL/min/1.73 m2 and 1.8 g/gCr, respectively. The baseline systolic and diastolic blood pressures were 131.4 and 71.0 mm Hg, respectively. The mean percent change in the UPCR was −3.8% in the azilsartan group and 30.8% in the candesartan group at the 1st endpoint (p = 0.0004), and 6.1% in the azilsartan group and 25.8% in the candesartan group at the 2nd (final) endpoint (p = 0.029). The incidence of adverse events, including eGFR levels and serum potassium levels, was not significantly different between the groups. Conclusion: A 20 mg azilsartan dose had potent antiproteinuric effects compared with an 8 mg candesartan dose, without an increase in adverse events. Azilsartan may provide renal protection in addition to antihypertensive effects in CKD patients.
Maternal Myometrium Metabolomic Profiles in Labor: Preliminary Results
Authors: Qian Xueya , Wang Lele , Lin Baohua , Luo Yihong , Chen Yunshan , Liu Huishu
Published: March 2021

Introduction: Parturition involves multiple complex metabolic processes that supply essential metabolites to facilitate fetal delivery. Little is known about the dynamic metabolic responses during labor. Objective: To profile the changes of myometrial metabolites between nonlabor and labor. Methods: The study involved 30 women in nonlabor and 30 in labor who underwent cesarean section. The characteristics of myometrial metabolite changes during parturition were explored through untargeted metabolomic analysis. Data were analyzed by multivariate and univariate statistical analysis. Results: Partial least squares-discriminant analysis plots significantly differentiated between the groups. In total, 392 metabolites were significantly distinct between the groups, among which lipid molecules were predominant. A 75% increase in fatty acids, 67% increase in fatty acid carnitines, 66% increase in glycerophospholipids, 83% increase in mono- and diacylglycerols, and 67% decrease in triacyclglycerols were observed in the patients during labor. Most glucose, amino acid, and steroid hormone metabolism also slightly increased in labor. Conclusions: An increase in lipolysis, fatty acid oxidation, amino acid catabolism, and steroid hormone metabolism was observed during parturition. The change of lipolysis and fatty acid oxidation is the most significant.
Bone-Anchored and Closed Skin Bonebridge Implant in Adults: Hearing Performances and Quality of Life
Authors: Garcier Martin , Lavedrine Angela , Gagneux Claude , Eluecque Thierry , Bozorg Grayeli Alexis
Published: March 2021

Introduction: Bonebridge® is a novel active bone-anchored hearing implant. The purpose of this study was to evaluate the ease of implantation, the hearing performances, and the patient-reported benefit. Materials and Methods: This is a prospective cross-sectional study of 24 consecutive adult patients implanted for a mixed hearing loss (13 chronic otitis media (COM) and 11 other aetiologies). Twenty-one implants were placed in the retrosigmoid position and 3 in the mastoid. Audiometry, Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, as well as 5 implant-specific questions (analogue visual scale [AVS] 0–10 score), was administered. Results: Surgery lasted 73 ± 29.7 min on average. No major complication occurred. All patients were users at the last follow-up visit (median: 9-month range: 3–25). The average prosthetic gain was similar in COM and other aetiologies (43 ± 4.8 dB and 50 ± 7.2, respectively, not significant, Wilcoxon test). Bone-conduction thresholds were not deteriorated by surgery (Kruskal-Wallis test, not significant). APHAB scores improved in all categories except aversiveness (global score 45 ± 7.0% in COM and 32 ± 10.2% in others, not significant, and Wilcoxon test). Local pain (AVS: 3.23 ± 3.2, n = 16) and manipulation difficulties (3.1 ± 3.69) were low. The device was considered aesthetic (8.3 ± 2.49). Perfectible autonomy (5.0 ± 2.8) and difficulties wearing the implant during sport or at work (5.1 ± 3.47) were the weakest points. Conclusions: BoneBridge® implant provides reproducible results for the rehabilitation of mixed hearing losses and unilateral hearing loss.
To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease
Authors: Juskewitch Justin E. , Tauscher Craig D. , Moldenhauer Sheila K. , Schieber Jennifer E. , Jacob Eapen K. , DiGuardo Margaret A.
Published: March 2021

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.
IgG4 Expression in Patients with Eosinophilic Otitis Media
Authors: Takahashi Masahiro , Oka Aiko , Kariya Shin , Gion Yuka , Sato Yasuharu , Iwasaki Satoshi , Oyamada Shogo , Matsubara Atsushi , Okano Mitsuhiro
Published: March 2021

Objective: Eosinophilic otitis media (EOM) is an intractable middle ear disease recognized by an eosinophil enriched middle ear effusion and mucosa. Although precise pathogenesis of EOM remains unclear, it is characterized by type 2 inflammation. Since IgG4 is an IgG subclass induced by type 2 cytokines such as IL-4 and IL-13, we sought to characterize and compare local IgG4 expression in patients with and without EOM. Methods: Twelve patients with bilateral profound hearing loss, 9 of which underwent a cochlear implant surgery, were enrolled in this study (6 with EOM and 6 without EOM). The surgical specimens were harvested during surgery and were subjected to IgG4 immunostaining. Result: The middle ear mucosa showed the presence of a large number of IgG4-positive cells in patients with EOM, which was significantly higher than that in patients without EOM. Conclusion: Local IgG4 expression was observed in patients with EOM in comparison to those without EOM, suggesting that IgG4 contributes to EOM pathogenesis.
Using Disposable Membrane Cell Collector to Enrich Lung Adenocarcinoma Cells in Bloody Pleural Effusion for Anaplastic Lymphoma Kinase Fusion Gene Detection
Authors: Guo Xiao , Zhao Jingxia , Du Yun , Liu Ying , Ma Yang , Wang Rui , Ji Xiaokun , Wu Juan , Dong Lvli
Published: March 2021

Purpose: For anaplastic lymphoma kinase (ALK) gene detection, the centrifugal sedimentation method (CSM) and cell block method (CBM) are commonly used to process samples of bloody pleural effusions (BPEs). However, in practice, the impurity content in the processed samples often affects the results and even leads to the detection failure. The purpose of this study was to establish a cell enrichment method (CEM) by using a disposable membrane cell collector to remove blood and inflammatory cells and enrich lung adenocarcinoma cells in BPE for more efficient RNA extraction and ALK gene detection. Materials and Methods: CEM proposed in this study and the traditional CSM and CBM were used to treat BPE samples collected from 37 lung adenocarcinoma patients. A DeNovix DS-11 ultraviolet spectrophotometer was used to measure the concentration and purity of extracted RNA. Amplification refractory mutation systems (ARMS) and ABI 7500 fluorescence qPCR were used to detect ALK gene. Through statistical analysis, the CEM was compared with the CSM and CBM in RNA concentration, purity, and ALK gene detection results. Results: The concentration of RNA extracted by using the CEM was significantly higher than that extracted by using the CBM and CSM (p < 0.001). The purity of RNA extracted by using the CEM was significantly higher than that by the other 2 methods (p = 0.011, p = 0.005). ALK gene testing with PCR was successful in all the samples using the CEM, but 2 cases by the CSM and 1 case by the CBM failed. Conclusions: Using the disposable membrane cell collector to process BPE of lung adenocarcinoma patients for RNA extraction and ALK gene detection is more effective and successful compared with the traditional methods, and it is suggested to be further applied and popularized in clinical practice.
A History of Asthma Increases the Risk of Bullous Pemphigoid: Insights from a Large Population-Based Study
Authors: Kridin Khalaf , Ludwig Ralf J. , Tzur Bitan Dana , Cohen Arnon D.
Published: March 2021

Background: Bullous pemphigoid (BP) and asthma both share a pathogenic role of eosinophils and immunoglobulin E (IgE) and favorable response for corticosteroids and omalizumab. However, the association between these conditions is yet to be investigated. We sought to estimate the risk of having BP among patients previously diagnosed with asthma and to characterize patients with coexistent BP and asthma. Methods: Utilizing the dataset of Clalit Health Services, a population-based case-control study was conducted comparing BP patients (n = 3,924) with age-, sex-, and ethnicity-matched control subjects (n = 19,280) regarding the presence of asthma. Logistic regression models were utilized for univariate and multivariate analyses. Results: The prevalence of preceding asthma was higher in patients with BP than in control subjects (11.1 vs. 7.9%, respectively; p < 0.001). A history of asthma was associated with a 50% increase in the risk of BP (OR 1.45; 95% CI 1.30–1.62). The association was not altered greatly after adjusting for demographics (adjusted OR 1.43; 95% CI 1.28–1.61) as well as for demographics and comorbidities (adjusted OR 1.40; 95% CI 1.25–1.57). The average (SD) latency between the diagnosis of asthma and the development of BP was 12.5 (14.7) years. When compared with other patients with BP, those with a dual diagnosis of BP and asthma were older, had higher BMI, and were more frequently managed by corticosteroids and immunosuppressive and immunomodulatory adjuvants. Conclusions: Asthma confers a predisposition to the development of BP. Awareness of this association may be of help for physicians managing patients with BP and asthma. Further research is required to elucidate the mechanism underlying this observation.
Elevated Serum Trimethylamine N-Oxide Levels Are Associated with Mortality in Male Patients on Peritoneal Dialysis
Authors: Fu Dongying , Shen Jiani , Li Wei , Wang Yating , Zhong Zhong , Ye Hongjian , Huang Naya , Fan Li , Yang Xiao , Yu Xuqing , Zhou Yi , Mao Haiping
Published: March 2021

Background: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. Methods: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. Results: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8–61.0) μM. During a median follow-up of 63.7 months (IQR, 43.9–87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01–1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07–1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02–1.94; p = 0.038) in men but not in women. Conclusions: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.
Combination of HAI-FUDR and Systemic Gemcitabine and Cisplatin in Unresectable Cholangiocarcinoma: A Dose Finding Single Center Study
Authors: Pietge Heike , Sánchez-Velázquez Patricia , Akhoundova Dilara , Siebenhüner Alexander , Winder Thomas , Bachmann Helga , Nguyen-Kim Thi Dan Linh , Breitenstein Stefan , Knuth Alexander , Petrowsky Henrik , Pestalozzi Bernhard , Clavien Pierre-Alain , Samaras Panagiotis
Published: March 2021

Background: Unresectable cholangiocarcinoma has a poor prognosis and treatment options are limited. Combined systemic and intrahepatic chemotherapy may improve local control and enable downsizing. The aim of this study was to determine the maximum tolerated dose (MTD) of intravenous gemcitabine combined with intravenous cisplatin and hepatic arterial infusion (HAI) with floxuridine (FUDR) in patients with unresectable intrahepatic or hilar cholangiocarcinoma. Methods: Twelve patients were treated within a 3 + 3 dose escalation algorithm with 600, 800, or 1,000 mg/m2 gemcitabine and predefined doses of cisplatin 25 mg/m2 on days 1 and 8, q21, for 4 cycles, and FUDR 0.2 mg/kg on days 1–14 as continuous HAI, q28, for 3 cycles. Safety and toxicity as well as resectability rates after 3 months and preliminary survival data are reported. Results: The determined MTD for gemcitabine was 800 mg/m2. Dose limiting toxicities were neutropenic fever and biliary tract infections. In total, 27% of the patients showed partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, the 3-year overall survival rate was 33%, median overall survival 23.9 months (range 1–49), and median progression-free survival 10.1 months (range 2–40). Conclusions: Intravenous gemcitabine/cisplatin plus HAI-FUDR is feasible and appears effective for disease control. Larger prospective studies evaluating this triplet combination are warranted.
Corneocytes: Relationship between Structural and Biomechanical Properties
Authors: Évora Ana S. , Adams Michael J. , Johnson Simon A. , Zhang Zhibing
Published: March 2021

Background: Skin is the interface between an organism and the external environment, and hence the stratum corneum (SC) is the first to withstand mechanical insults that, in certain conditions, may lead to integrity loss and the development of pressure ulcers. The SC comprises corneocytes, which are vital elements to its barrier function. These cells are differentiated dead keratinocytes, without organelles, composed of a cornified envelope and a keratin-filled interior, and connected by corneodesmosomes (CDs). Summary: The current review focusses on the relationship between the morphological, structural, and topographical features of corneocytes and their mechanical properties, to understand how they assist the SC in maintaining skin integrity and in responding to mechanical insults. Key Messages: Corneocytes create distinct regions in the SC: the inner SC is characterized by immature cells with a fragile cornified envelope and a uniform distribution of CDs; the upper SC has resilient cornified envelopes and a honeycomb distribution of CDs, with a greater surface area and a smaller thickness than cells from the inner layer. The literature indicates that this upward maturation process is one of the most important steps in the mechanical resistance and barrier function of the SC. The morphology of these cells is dependent on the body site: the surface area in non-exposed skin is about 1,000–1,200 μm2, while for exposed skin, for example, the cheek and forehead, is about 700–800 μm2. Corneocytes are stiff cells compared to other cellular types, for example, the Young’s modulus of muscle and fibroblast cells is typically a few kPa, while that of corneocytes is reported to be about hundreds of MPa. Moreover, these skin cells have 2 distinct mechanical regions: the cornified envelope (100–250 MPa) and the keratin matrix (250–500 MPa).
Multiple Sclerosis and Incidence of Urinary and Fecal Incontinence in Almost 9,000 Patients Followed Up for up to 10 Years in Germany
Authors: Jacob Louis , Tanislav Christian , Kostev Karel
Published: March 2021

Background: There is a lack of large studies on urinary (UI) and fecal incontinence (FI) following multiple sclerosis (MS) diagnosis. Thus, our goal was to investigate the association between MS and the incidence of UI and FI in patients followed up for up to 10 years in Germany. Methods: This study included patients who received an initial documentation of MS diagnosis in general practices in Germany during 2005–2018 (index date). Patients without MS were matched (1:1) to those with MS using propensity scores based on sex, age, index year, follow-up time (in years), general practice, and the Charlson Comorbidity Index score (index date: a randomly selected visit date). Results: This retrospective study included 4,461 patients with MS and 4,461 patients without MS (69.9% women; mean [SD] age 44.2 [12.7] years). Within 10 years of index date, a higher proportion of patients with MS were diagnosed with UI (11.7 vs. 3.2%) and FI (2.3 vs. 0.5%; p values <0.001) than those without MS. MS was further found to be associated with both UI (hazard ratio [HR] = 3.85) and FI (HR = 5.38; p values <0.001) in the Cox regressions. Conclusions: UI and FI are frequent complications of MS, and the presence of these complications should be regularly assessed in primary care practices.
The Comparison of Sarcopenia Diagnostic Criteria using AWGS 2019 with the Other Five Criteria in West China
Authors: Liu Xiaolei , Hou Lisha , Zhao Wanyu , Xia Xin , Hu Fengjuan , Zhang Gongchang , Hao Qiukui , Zhou Lixing , Liu Yixin , Ge Meiling , Zhang Yan , Yue Jirong , Dong Birong
Published: March 2021

Introduction: The aim of this study was to investigate the prevalence and associated factors of sarcopenia defined by different criteria in community-dwelling adults of west China using the baseline data of West-China Health and Aging Trend (WCHAT) study. Methods: Adults aged 50 years or older in communities of Yunnan, Guizhou, Sichuan, and Xinjiang provinces were enrolled in this study. We applied 6 ­diagnostic criteria (AWGS 2019, AWGS 2014, EWGSOP1, ­EWGSOP2, IWGS, and FNIH) to define sarcopenia. Muscle mass was measured based on bioimpedance analysis. Handgrip strength and walking speed were recorded, respectively. Different variables like anthropometry measures, lifestyles, chronic disease, and blood test were collected. Results: We included 4,500 participants. The prevalence of sarcopenia was 22.8, 19.3, 57.1, 11.8, 24.1, and 18.1% according to the AWGS 2019, AWGS 2014, EWGSOP 1, EWGSOP 2, IWGS, and FNIH criteria, respectively. We found that serum albumin level was independently associated with sarcopenia using AWGS 2019 and IWGS. And vitamin D level was independently associated with sarcopenia using AWGS 2014, ­EWGSOP2, and FNIH. While age, depressive status, BMI, hemoglobin, vitamin D, and insulin level were all significantly associated with sarcopenia using AWGS 2014, but all of these factors were not significant using AWGS 2019. Conclusions: Sarcopenia was highly prevalent in west China regardless of the diagnostic criteria. Serum albumin and vitamin D level were mostly associated with sarcopenia defined by different criteria. While most risk factors associated with the AWGS 2014-defined sarcopenia exhibited no consistent pattern with AWGS 2019, the validity of the AWGS 2019 consensus needs to be confirmed in further prospective studies.
Assessing Pragmatic Language Skills in Adults with Major Depressive Disorder: An Exploratory Study
Authors: Zurlo Maria Clelia , Ruggiero Maura
Published: March 2021

Introduction: There is increasing evidence that major depressive disorder (MDD) is associated with significant pragmatic language impairments. However, there is a lack of studies that use standardized tools and simultaneously investigate all pragmatic language skills among MDD patients. The aim of this study was to propose a more thorough investigation of all pragmatic language skills in patients with MDD. Methods: Twenty adults (aged 22–65) with a DSM-5 diagnosis of MDD were assessed using BLED Santa Lucia (Batteria sul Linguaggio dell’Emisfero Destro Santa Lucia), a battery designed to evaluate pragmatic language skills (comprehension of inferences, of picture and written metaphors, of indirect requests, of humoristic expressions, and of prosody). The performance of the MDD participants on all BLED Santa Lucia subscales was compared to 20 healthy control subjects (aged 20–60) matched for gender, age, years of education, and employment status. Results: MDD patients performed poorer than controls in comprehension of inferences (p < 0.01), picture metaphors (p < 0.001), written metaphors (p < 0.001), indirect requests (p < 0.01), humoristic expression (p < 0.05), and prosody (p < 0.05). Conclusions: All pragmatic language skills can be significantly impaired in MDD patients. A valid assessment of all pragmatic language skills can allow, for each patient, the definition of a specific profile of risk and protective factors before and during psychotherapy.
Applications of Computational Pathology in Head and Neck Cytopathology
Authors: Lollie Trang K. , Krane Jeffrey F.
Published: March 2021

Background: The application of computational technology to head and neck cytology material has been explored experimentally in several areas with a variety of potential applications. Summary: This review summarizes the application of these techniques to the diagnosis of thyroid, salivary gland, and other head and neck fine-needle aspiration specimens. Current limitations and potential future applications in diagnosis are discussed along with the possibilities for therapeutic applications of computational methodology. Key Message: Particularly promising applications include resolving diagnostic uncertainty in indeterminate thyroid aspirates and assessing the tumor microenvironment in response to immunotherapy for squamous cell carcinoma.
The Accuracy of the Surgical Peritoneal Cancer Index in Patients with Peritoneal Metastases of Colorectal Cancer
Authors: de Boer Nadine L. , Brandt-Kerkhof Alexandra R.M. , Madsen Eva V.E. , Doukas Michael , Verhoef Cornelis , Burger Jacobus W.A.
Published: March 2021

Introduction: The peritoneal cancer index (PCI) is one of the most important prognostic factors in patients with peritoneal metastases from colorectal cancer undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The PCI is determined during laparotomy by 2 experienced surgeons and plays a major role in the decision to proceed with CRS-HIPEC. The primary objective of this study was to determine the accuracy of the surgical PCI (sPCI) by comparing it with the PCI confirmed by the pathologist (pPCI). Methods: All consecutive patients who underwent CRS-HIPEC for colorectal peritoneal metastases between February 2015 and June 2018 were identified. Relevant patient- and tumor-related characteristics were collected. Results: In total, 119 patients were included, 60 males (50.4%). The median age was 64 (IQR 55–71). The median sPCI (sPCI = 11, IQR 6–16) was significantly higher than the median pPCI (pPCI = 8, IQR 3–13, p < 0.001). The total pPCI was lower than the total sPCI in 80 patients (67.2%). In 21 patients (17.6%), the sPCI was overestimated with ≥5 points. Small lesions are more likely to be negative. In patients that underwent resection of their primary tumor prior to CRS-HIPEC, the difference between the sPCI and pPCI was significantly larger (p < 0.05). Conclusions: Surgical calculation of the PCI often results in overestimation. Far-reaching consequences are tied to the macroscopic evaluation of the sPCI, but this evaluation seems not very reliable.
Higher Prevalence of Concurrent Thrombocytopenia in Patients Receiving Continuous Renal Replacement Therapy in the Cardiac Intensive Care Unit
Authors: Griffin Jan M. , Tariq Anam , Menez Steven , Kyeso Yousuf , Chedid Alice , Ramakrishnan Viswanathan , Schulman Steve P. , Sperati C. John , Choi Michael J. , McEvoy J. William , McMahon Blaithin A.
Published: March 2021

Introduction: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). Objective: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. Methods: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. Results: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32–3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. Conclusion: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.
Development of Testis Cords and the Formation of Efferent Ducts in Xenopus laevis: Differences and Similarities with Other Vertebrates
Authors: Li Yuanyuan , Li Jinbo , Cai Man , Qin Zhanfen
Published: March 2021

The knowledge of testis development in amphibians relative to amniotes remains limited. Here, we used Xenopus laevis to investigate the process of testis cord development. Morphological observations revealed the presence of segmental gonomeres consisting of medullary knots in male gonads at stages 52–53, with no distinct gonomeres in female gonads. Further observations showed that cell proliferation occurs at specific sites along the anterior-posterior axis of the future testis at stage 50, which contributes to the formation of medullary knots. At stage 53, adjacent gonomeres become close to each other, resulting in fusion; then (pre-)Sertoli cells aggregate and form primitive testis cords, which ultimately become testis cords when germ cells are present inside. The process of testis cord formation in X. laevis appears to be more complex than in amniotes. Strikingly, steroidogenic cells appear earlier than (pre-)Sertoli cells in differentiating testes of X. laevis, which differs from earlier differentiation of (pre-)Sertoli cells in amniotes. Importantly, we found that the mesonephros is connected to the testis gonomere at a specific site at early larval stages and that these connections become efferent ducts after metamorphosis, which challenges the previous concept that the mesonephric side and the gonadal side initially develop in isolation and then connect to each other in amphibians and amniotes.
UAE Resident Users’ Perceptions of Healthcare Applications from Dubai Health Authority: Preliminary Insights
Authors: AlSuwaidi Shamsa , Moonesar Immanuel Azaad
Published: March 2021

Background: Innovations in healthcare are a way to sustain and improve health outcomes, usually done in a cost-effective way. Thus, the Dubai Health Authority (DHA) is keen on launching the best innovations in all areas such as health apps, telecommunications, electronic patient health records, and others. Objectives: DHA apps users within the United Arab Emirates (UAE) were studied to determine the extent they were satisfied with the available medical health apps; there are limited studies on users’ perceptions on health innovations in the UAE. Method and Results: The quantitative methodology included data collection from a sample of 396 apps users. The technology acceptance model (TAM) provided an appropriate framework for this research, independent variables included gender, nationality, education, and age, and the dependent variables included the users’ perceptions related to usefulness, ease of use, and usability as well as satisfaction. The results of the study revealed a statistically significant difference based on the abovementioned independent variables. Conclusion: The research adds value for policymakers when considering and evaluating the current health apps available in the DHA; the research findings could positively influence public policies for the development of health innovations across the UAE region. Future research should aim to include other factors that may have an influence on the adoption of technology and uncover further reasons that motivate or discourage users.
Improving the Dutch Newborn Screening for Central Congenital Hypothyroidism by Using 95% Reference Intervals for Thyroxine-Binding Globulin
Authors: Stroek Kevin , Heijboer Annemieke C. , van Veen-Sijne Marja , Bosch Annet M. , van der Ploeg Catharina P.B. , Zwaveling-Soonawala Nitash , de Jonge Robert , van Trotsenburg A.S. Paul , Boelen Anita
Published: March 2021

Introduction: Newborn screening (NBS) for congenital hypothyroidism (CH) in the Netherlands consists of thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG) measurements to detect thyroidal CH and central CH (CH-C). CH-C is detected by T4 or a calculated T4/TBG ratio, which serves as an indirect measure of free T4. TSH and TBG are only measured in the lowest 20 and 5% of daily T4 values, respectively. A recent evaluation of the Dutch NBS for CH showed that the T4 and T4/TBG ratio contribute to the detection of CH-C but also lead to a low positive predictive value (PPV). Dried blood spot (DBS) reference intervals (RIs) are currently unknown and may contribute to improvement of our NBS algorithm. Materials and Methods: RIs of T4, TSH, TBG, and the T4/TBG ratio were determined according to Clinical & Laboratory Standards Institute guidelines in heel puncture cards from routine NBS in both sexes and at the common NBS sampling ages. Scatter plots were used to compare the healthy reference population to previously published data of CH-C patients and false positives. Results: Analyses of 1,670 heel puncture cards showed small differences between subgroups and led to the formulation of total sample DBS RIs for T4 (56–118 nmol/L), TSH (<2.6 mIU/L), TBG (116–271 nmol/L), and the T4/TBG ratio (>20). 46% of false-positive referrals based on T4 alone had a TBG below the RI, indicating preventable referral due to partial TBG deficiency. One case of CH-C also had partial TBG deficiency (TBG 59 and T4 12 nmol/L blood). Discussion/Conclusion: Established DBS RIs provided possibilities to improve the PPV of the Dutch CH NBS algorithm. We conclude that by taking partial TBG deficiency into account, approximately half of T4 false-positive referrals may be prevented while maintaining NBS sensitivity at the current level.
Machine Learning for Prediction and Risk Stratification of Lupus Nephritis Renal Flare
Authors: Chen Yinghua , Huang Siwan , Chen Tiange , Liang Dandan , Yang Jing , Zeng Caihong , Li Xiang , Xie Guotong , Liu ZhiHong
Published: March 2021

Background: Renal flare of lupus nephritis (LN) is strongly associated with poor kidney outcomes, and predicting renal flare and stratifying its risk are important for clinical decision-making and individualized management to reduce LN flare. Methods: We randomly divided 1,694 patients with biopsy-proven LN, who had achieved remission after treatment, into a derivation cohort (n = 1,186) and an internal validation cohort (n = 508), at a ratio of 7:3. The risk of renal flare 5 years after remission was predicted using an eXtreme Gradient Boosting (XGBoost) method model, developed from 59 variables, including demographic, clinical, immunological, pathological, and therapeutic characteristics. A simplified risk score prediction model (SRSPM) was developed from important variables selected by XGBoost model using stepwise Cox regression for practical convenience. Results: The 5-year relapse rates were 39.5% and 38.2% in the derivation and internal validation cohorts, respectively. Both the XGBoost model and the SRSPM had good predictive performance, with a C-index of 0.819 (95% confidence interval [CI]: 0.774–0.857) and 0.746 (95% CI: 0.697–0.795), respectively, in the validation cohort. The SRSPM comprised 6 variables, including partial remission and endocapillary hypercellularity at baseline, age, serum Alb, anti-dsDNA, and serum complement C3 at the point of remission. Using Kaplan-Meier analysis, the SRSPM identified significant risk stratification for renal flares (p < 0.001). Conclusions: Renal flare of LN can be readily predicted using the XGBoost model and the SRSPM, and the SRSPM can also stratify flare risk. Both models are useful for clinical decision-making and individualized management in LN.
Appendicular Muscle Mass, Thigh Intermuscular Fat Infiltration, and Risk of Fall in Postmenopausal Osteoporotic Elder Women
Authors: Vitale Jacopo Antonino , Messina Carmelo , Albano Domenico , Fascio Edoardo , Galbusera Fabio , Corbetta Sabrina , Sconfienza Luca Maria , Banfi Giuseppe
Published: March 2021

Background: The association between the quantity and composition of skeletal muscle and the decline in physical function in elderly is poorly understood. Therefore, the primary aim of this cross-over study was to investigate the association between thigh intermuscular adipose tissue (IMAT) infiltration, appendicular muscle mass, and risk of fall in postmenopausal osteoporotic elder women. Second, we examined the differences in muscle mass, IMAT, and risk of fall in the same sample of older subjects after being classified as sarcopenic or nonsarcopenic on the basis of the dual-energy X-ray absorptiometry (DXA)-based Appendicular Skeletal Muscle Mass Index (ASMMI). Methods: Twenty-nine subjects (age: 72.4 ± 6.8; BMI: 23.0 ± 3.3; and T-score: −2.7 ± 0.2) completed the following clinical evaluations: (1) whole-body DXA to assess the ASMMI; (2) magnetic resonance to determine the cross-sectional muscle area (CSA) and IMAT of thigh muscles, expressed both in absolute (IMATabs) and relative (IMATrel) values; and (3) risk of fall assessment through the OAK system (Khymeia, Noventa Padovana, Italy). The existence of a correlation between the risk of fall (OAK scores, an automated version of the Brief-BESTest) and the clinical parameters (ASMMI, CSA, IMATrel, and IMATabs) was tested by the Pearson’s correlation index while data homogeneity between sarcopenic and nonsarcopenic subjects was tested through unpaired Student t tests or with the Mann-Whitney rank test. Effect sizes (ES) were used to determine the magnitude of the effect for all significant outcomes. Results: Eleven subjects were classified as sarcopenic and 18 as nonsarcopenic based on their ASMMI (cutoff value: 5.5 kg/m2). A positive correlation between OAK and CSA was observed (r2 = 0.19; p = 0.033), whereas a negative correlation between OAK and IMATrel was detected (r2 = 0.27; p = 0.009). No correlations were observed between OAK and ASMMI and between ASMMI and IMATrel. Sarcopenic subjects showed significantly lower weight (p = 0.002; ES = 1.30, large), BMI (p = 0.0003; ES = 1.82, large), CSA (p = 0.010; ES = 1.17, moderate), and IMATabs (p = 0.022; ES = 1.63, large) than nonsarcopenic individuals, whereas OAK scores and IMATrel were similar between groups. Discussion/Conclusion: Increased IMAT and lower CSA in the thigh muscles are associated with higher risk of fall while ASMMI, a value of appendicular muscle mass, was not associated with physical performance in older adults.