bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial Risk Profiles and Colorectal Cancer Screening: A Latent Profile Analysis in a Colorectal Cancer Screening Intervention Setting
Authors: Shokar Navkiran K. , Dwivedi Alok , Molokwu Jennifer C.
Published: August 2023

Health behavior theories have identified predictors of colorectal cancer screening. This study aimed to determine the psychosocial profiles of a predominantly Hispanic population of primarily Mexican origin receiving a colorectal cancer screening intervention and whether a specific combination of psychosocial profiles modified the effect of colorectal cancer screening intervention on colorectal cancer screening uptake.

A total of 467 participants aged 50 to 75 years due for colorectal cancer screening received an educational intervention. Latent profile analysis (LPA) was performed on baseline psychosocial constructs to identify the homogenous clustering of individuals with similar psychosocial constructs. In addition, colorectal cancer screening rates and changes in psychosocial scores between the latent groups were compared.

Three psychosocial profiles, including a low benefit and high susceptibility group (LBHS), a high benefit and low susceptibility group (HBLS), and a high barrier and high susceptibility group (HBHS), were identified in this study. The HBLS group had the lowest susceptibility, with no improvement in benefits and barriers. This group had the lowest screening rate (80.85%) compared with 88.8% in LBHS and 86.3% in HBHS following the intervention. Finally, the intervention effect size on psychosocial score changes was smaller in HBLS than in other groups.

This subgroup analysis suggests that colorectal cancer educational interventions should be tailored to improve the benefits and barriers among individuals with high susceptibility scores.

Prevention Relevance:

This LPA analysis provides some direction for tailoring colorectal cancer educational interventions to improve the benefits and barriers among individuals with high susceptibility scores in hard-to-screen populations such as our border population.
MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer
Authors: Engstrom Lars D. , Aranda Ruth , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Trinh David , Hebbert Allan , Smith Christopher R. , Kulyk Svitlana , Lawson J. David , He Leo , Hover Laura D. , Fernandez-Banet Julio , Hallin Jill , Vanderpool Darin , Briere David M. , Blaj Alice , Marx Matthew A. , Rodon Jordi , Offin Michael , Arbour Kathryn C. , Johnson Melissa L. , Kwiatkowski David J. , Jänne Pasi A. , Haddox Candace L. , Papadopoulos Kyriakos P. , Henry Jason T. , Leventakos Konstantinos , Christensen James G. , Shazer Ronald , Olson Peter
Published: August 2023

Previous studies implicated protein arginine methyltransferase 5 (PRMT5) as a synthetic lethal target for MTAP-deleted (MTAP del) cancers; however, the pharmacologic characterization of small-molecule inhibitors that recapitulate the synthetic lethal phenotype has not been described. MRTX1719 selectively inhibited PRMT5 in the presence of MTA, which is elevated in MTAP del cancers, and inhibited PRMT5-dependent activity and cell viability with >70-fold selecti­vity in HCT116 MTAP del compared with HCT116 MTAP wild-type (WT) cells. MRTX1719 demonstrated dose-dependent antitumor activity and inhibition of PRMT5-dependent SDMA modification in MTAP del tumors. In contrast, MRTX1719 demonstrated minimal effects on SDMA and viability in MTAP WT tumor xenografts or hematopoietic cells. MRTX1719 demonstrated marked antitumor activity across a panel of xenograft models at well-tolerated doses. Early signs of clinical activity were observed including objective responses in patients with MTAP del melanoma, gallbladder adenocarcinoma, mesothelioma, non–small cell lung cancer, and malignant peripheral nerve sheath tumors from the phase I/II study.

Significance:

PRMT5 was identified as a synthetic lethal target for MTAP del cancers; however, previous PRMT5 inhibitors do not selectively target this genotype. The differentiated binding mode of MRTX1719 leverages the elevated MTA in MTAP del cancers and represents a promising therapy for the ∼10% of patients with cancer with this biomarker.

See related commentary by Mulvaney, p. 2310.

This article is featured in Selected Articles from This Issue, p. 2293
Circadian Activity Rhythms and Psychopathology in Major Depressive Episodes
Authors: Salvatore Paola , Indic Premananda , Khalsa Harimandir K. , Tohen Mauricio , Baldessarini Ross J. , Maggini Carlo
Published: August 2023

Background: Identifying suicidal risk based on clinical assessment is challenging. Suicidal ideation fluctuates, can be downplayed or denied, and seems stigmatizing if divulged. In contrast, vitality is foundational to subjectivity in being immediately conscious before reflection. Including its assessment may improve detection of suicidal risk compared to relying on suicidal ideation alone. We hypothesized that objective motility measures would be associated with vitality and enhance assessment of suicidal risk. Methods: We evaluated 83 adult-psychiatric outpatients with a DSM-5 bipolar (BD) or major depressive disorder (MDD): BD-I (n = 48), BD-II (20), and MDD (15) during a major depressive episode. They were actigraphically monitored continuously over 3 weekdays and self-rated their subjective states at regular intervals. We applied cosinor analysis to actigraphic data and analyzed associations of subjective psychopathology measures with circadian activity parameters. Results: Actigraphic circadian mesor, amplitude, day- and nighttime activity were lower with BD versus MDD. Self-rated vitality (wish-to-live) was significantly lower, self-rated suicidality (wish-to-die) was higher, and their difference was lower, with BD versus MDD. There were no other significant diagnostic differences in actigraphic sleep parameters or in self-rated depression, dysphoria, or anxiety. By linear regression, the difference between vitality and passive suicidal ideation was strongly positively correlated with mesor (p < 0.0001), daytime activity (p < 0.0001), and amplitude (p = 0.001). Conclusions: Higher circadian activity measures reflected enhanced levels of subjective vitality and were associated with lesser suicidal ideation. Current suicidal-risk assessment might usefully include monitoring of motility and vitality in addition to examining negative affects and suicidal thinking.
The Agreement of the Nomogram Tool and Ultrasound Biomicroscopy Images in Calculating Ultrasound Cycloplasty Probe Model in Chinese Patients
Authors: Zheng Shaoyang , Wang Dingqiao , Huang Zhihong , Wang Zhenyu , Liu Yuan , Chen Liming , Jin Ling , Tan Yuheng , Lin Mingkai , Zuo Chengguo
Published: August 2023

Purpose: The aim of the study was to compare and explore the agreement between the nomogram tool and ultrasound biomicroscopy (UBM) images method to calculate the ultrasound cycloplasty (UCP) probe model in Chinese glaucoma patients. Methods: Retrospective analysis of Chinese glaucoma patients who visited Zhongshan Ophthalmic Center in Guangzhou from January to December 2019 and were eligible for UCP surgery. Visual acuity, intraocular pressure (IOP), ocular axial length (AL), and horizontal corneal diameter (white to white [WTW]) were measured. UBM images with clear ciliary body imaging and AL and WTW data were sent to trained personnel for probe model measurements. The data calculated by both methods were analyzed using unweighted and weighted κ statistics. The level of agreement refers to Landis and Koch’s guideline for the strength of agreement indicated with weighted κ values. Results: 1,061 eyes of 642 patients were involved, with a mean age of 61.66 ± 11.66 years. Their best-corrected visual acuity converted to logarithm of minimal-angle-of-resolution (logMAR) scores of −0.18–3.00 with a mean value of 0.69 ± 0.77. IOP was 22.0–60.0 mm Hg with a mean of 27.97 ± 5.66 mm Hg. The mean AL and WTW were 22.88 ± 1.33 (19.15–32.14) mm and 11.52 ± 0.49 (10.00–12.90) mm, respectively. The agreement between the two methods was fair (weighted κ = 0.299), matching in 62.86% of eyes (weighted κ = 0.299, κ = 0.264). The agreement in primary open angle glaucoma, acute primary angle-closure glaucoma, chronic primary angle-closure glaucoma, and secondary glaucoma patients was 60.85% (weighted κ = 0.336, κ = 0.301), 65.06% (weighted κ = 0.146, κ = 0.127), 62.26% (weighted κ = 0.204, κ = 0.184), and 57.97% (weighted κ = 0.332, κ = 0.280) of eyes, respectively. Conclusion: The agreement between UBM images and the nomogram tool to calculate the UCP probe model of Chinese patients is at a fair level. The nomogram tool prefers to use larger probes. Improvements to the nomogram tool, such as including data from more ethnic groups and being able to calculate separately for different types of glaucoma, are needed to improve accuracy. The inclusion of parameters or images from more directions of the eye may help measure probe models more accurately for both the nomogram tool and the UBM image measurement.
Methylation of the Glucocorticoid Receptor Gene (NR3C1) in Adolescents with a History of Childhood Adversity Engaging in Non-Suicidal Self-Injury
Authors: Hammann Nicole , Kaess Michael , Rujescu Dan , Brunner Romuald , Hartmann Annette M. , Reichl Corinna
Published: August 2023

Introduction: Non-suicidal self-injury (NSSI) is a large phenomenon among adolescents, and adverse childhood experiences (ACEs) are a major risk factor in its development. Malfunctioning of the hypothalamus-pituitary-adrenal (HPA) axis has been repeatedly reported for ACE as well as for NSSI. The glucocorticoid receptor (GR) is essential for the correct functioning of the HPA axis, thus alterations in the expression of the GR through altered methylation of the GR gene (NR3C1) (and more specifically exon 1F) might contribute to the development of NSSI in individuals with a history of ACEs, as has been reported for different other mental disorders. Methods: In this case-control study, we compared the methylation levels of exon 1F of the GR gene (NR3C1-1F) in adolescents with engagement in NSSI (n = 67) and a healthy control group (HC; n = 47). We preserved buccal swabs and used a mass spectrometry-based method called EpiTYPER for analyzing mean methylation of NR3C1-1F. Results: Adolescents in the NSSI group reported significantly more ACEs. The mean methylation level was about 3% in both groups with no significant group differences. Furthermore, no significant relation was found between ACE and methylation of NR3C1-1F, neither in the overall sample nor in the NSSI or HC group. Conclusion: Our results are contradictory to previous research showing an increased methylation in individuals with ACE. Regarding relations between methylation of NR3C1-1F and mental disorders, previous studies reported inconsistent findings. Our study points to NSSI being either unrelated to methylation of NR3C1-1F or to yet not identified moderators on relations between methylation of NR3C1-1F and engagement in NSSI during adolescence.
Prevalence of Polycystic Ovarian Syndrome in Girls with a History of Idiopathic Central Precocious Puberty
Authors: Arcari Andrea Josefina , Freire Analía Verónica , Ballerini María Gabriela , Escobar María Eugenia , Díaz Marsiglia Yenifer María , Bergadá Ignacio , Ropelato María Gabriela , Gryngarten Mirta Graciela
Published: August 2023

Introduction: The prevalence of polycystic ovarian syndrome (PCOS) in adolescent girls is between 1 and 4.3%. It remains controversial whether women with a history of idiopathic central precocious puberty (ICPP) are at increased risk for PCOS. Our objective was to assess the prevalence of PCOS in adolescents with a history of ICPP compared with healthy adolescents and the prevalence of PCOS among ICPP girls who have received or not gonadotropin-releasing hormone analogue (GnRHa) treatment. Methods: We assessed post-menarcheal girls with a history of ICPP. Girls were evaluated at gynecological age ≥2.5 years. Data collected were age at menarche, menstrual cycle characteristics, BMI, clinical hyperandrogenism (HA), total and free testosterone levels. PCOS diagnosis was defined by criteria for adolescents. Subjects were also analyzed regarding whether or not they had received GnRHa treatment. Results: Ninety-four subjects were assessed, and 63 had been treated with GnRHa. Menstrual disorders were found in 29%, clinical HA in 36%, and biochemical HA in 23%. Twelve percent met the diagnostic criteria for PCOS. There was no difference in BMI or in the incidence of menstrual dysfunction or hyperandrogenemia between treated and untreated patients. A higher proportion of clinical HA was found in untreated patients when compared to treated girls. The relative risk (RR) of developing PCOS in ICPP girls was 2.5 compared to a population of healthy adolescents. This RR was not higher in patients who received treatment with GnRHa than in those who did not. Conclusion: Adolescent girls with a history of ICPP have an increased risk of PCOS. This risk seems not to be related to GnRHa treatment.
The Diagnostic Performance of Laboratory Tests of Neurosyphilis: A Systematic Review and Network Meta-Analysis
Authors: Ding Duyu , Gao Junhua , Zhang Wei , Xu Dongmei
Published: August 2023

Introduction: The gold standard for diagnosing neurosyphilis (NS) is currently unavailable; various laboratory parameters in cerebrospinal fluid (CSF) and blood can assist in the diagnosis. Methods: PubMed, Embase, and the Cochrane Library were searched. Studies utilizing laboratory tests to assist in the diagnosis of NS were included. The pooled indicators for diagnostic performance and their respective 95% confidence intervals (CIs) were calculated. We used the superiority index to test the superiority of a diagnostic test. Results: Eleven citations were included in the study. Albumin quotient, CSF-TPHA, CSF-EIA, CSF-LDH, CSF-WBC, CSF-CXCL13, FTA-ABS, CSF-PCR, RPR, CSF-TPPA, TRUST, and CSF-venereal diseases research laboratory (VDRL) were assessed in the studies included. The pooled estimates of sensitivity, specificity, AUC of SROC and their respective 95% CIs for CSF-TPPA and CSF-VDRL were 0.97 (0.17, 1.00), 0.84 (0.62, 0.95), 0.93 (0.91, 0.95) and 0.74 (0.59, 0.85), 0.99 (0.93, 1.00), 0.94 (0.91, 0.96), respectively. CSF-TPHA demonstrated the highest relative sensitivity. CSF-VDRL manifested the highest specificity. CSF-TPHA, TRUST, CSF-VDRL, CSF-EIA, and RPR ranked in the top five laboratory tests with superiority index. Conclusion: CSF-TPHA, TRUST, CSF-VDRL, CSF-EIA, and RPR indicate acceptable performance in detecting NS compared to other modalities. Comprehensive diagnostic strategies still play a significant role in the diagnosis of NS.
Does Prediction of Neonatal Mortality by the Observed/Expected Lung-To-Head Ratio Change during Pregnancy in Fetuses with Left Congenital Diaphragmatic Hernia?
Authors: Huntley Erin S. , Hernandez-Andrade Edgar , Fishel Bartal Michal , Papanna Ramesha , Bergh Eric P. , Lopez Suzanne , Soto Eleazar , Harting Matthew T. , Johnson Anthony
Published: August 2023

Introduction: The aim of this study was to evaluate prediction of neonatal mortality in fetuses with isolated left congenital diaphragmatic hernia (CDH) when the observed/expected lung-to-head ratio (O/E LHR) was estimated at two different gestational time points during pregnancy. Methods: Forty-four (44) fetuses with isolated left CDH were included. O/E LHR was estimated at the time of referral (first scan) and before delivery (last scan). The main outcome was neonatal death due to respiratory complications. Results: There were 10/44 (22.7%) perinatal deaths. The areas under (AU) the ROC curves were: first scan, 0.76, best O/E LHR cut-off 35.5% with 76% sensitivity and 70% specificity; last scan, AU-ROC 0.79, best O/E LHR cut-off 35.2%, with 79.0% sensitivity and 80% specificity. Considering an O/E LHR cut-off ≤35% to define high-risk fetuses at any examination, prediction for perinatal mortality showed: 80% sensitivity, 73.5% specificity, 47.1% positive and 92.6% negative predictive values, and 3.02 (95% CI 1.59–5.73) positive and 0.27 (95% CI 0.08–0.96) negative likelihood ratios. Prediction was similar in the two evaluations as 16/21 (76.2%) of fetuses considered at risk had an O/E LHR ≤35% in the two examinations; in the remaining 5 cases, two were identified only in the first and three only in the last scan. Conclusion: The O/E LHR is a good predictor of perinatal death in fetuses with left isolated CDH. Approximately 80% of fetuses at risk of perinatal death can be identified with an O/E LHR ≤35%, and 90% of them will have similar O/E LHR values at the first and at the last ultrasound examinations prior to delivery. In general, 88.6% of all CDH fetuses have a similar severity classification based on the O/E LHR at the first diagnostic ultrasound or at the ultrasound examination prior to delivery.
Pleuraerkrankungen: Multidisziplinäre Teams aus Pneumologen und Thoraxchirurgen führen zu besserer Diagnose und Therapie
Authors: Hekmat Khosro
Published: August 2023

Medical thoracoscopy/pleuroscopy has become, after bronchoscopy, the second most commonly utilized endoscopic procedure in interventional pulmonology. Due to their common origin, medical thoracoscopy/pleuroscopy and video-assisted thoracic surgery (VATS) are quite similar procedures technically. In contrast to the prevailing attitude that it should predominantly be performed by interventional pulmonologists, we believe that, like all hybrid-in-nature techniques, it should be implemented as part of a combined specialist care service/team. Herewith, we describe our attempt to establish a multidisciplinary pleural disease program during a difficult economic period or our country, comprising thoracic surgeons, pulmonologists and anesthesiologists, all of whom brought in their experience, expertise and resources to establish and develop the service resulting in a hybridization of the technique, with, as reported, quite favorable results.
The Epidemic Characteristics of Stroke Death from 2012 to 2021 in Chongqing, China
Authors: Ding Xianbin , Ding Rui , Chen Liling , Jiao Yan , Xu Jie , Zhang Guiting , Wang Qiuting , Xie Jiaxi , Gao Yang , Yang Xianxian
Published: August 2023

Introduction: Stroke has become a major disease that threatens the global population’s health and is a major public health problem that needs to be solved in China. Therefore, it is essential to analyze the trend of the mortality of stroke and its epidemic characteristic of stroke death. Methods: Death cases of stroke were reported to the national death registry system by the medical staff of all medical institutions, and the population data every year were obtained from District or County’s Statistic Bureau in Chongqing. They were analyzed to calculate the mortality, age-standardized mortality rate by Chinese standardization population (ASMRC), age-specific mortality, proportion, and annual percent of change (APC) according to the ICD-10 code. ASMRC was based on the standard population of the 6th census in China, 2010. The stroke mortality of each subgroup was compared using the χ2 test. Trend analysis was presented by APC. Results: The crude mortality of stroke increased from 96.29 per 100,000 in 2012 to 115.93 per 100,000 significantly, with the APC of 2.02% (t = 2.82, p = 0.022) in Chongqing. ASMRC of stroke was 56.47 per 100,000 in 2012 and 54.70 per 100,000 in 2021, and its trend change was stable (APC = −0.01, t = 0.07, p = 0.947). The crude mortality of stroke in males was higher than that in females every year (p < 0.05). The death proportion of intracerebral hemorrhage dwindled from 60.53% in 2012 to 49.88% in 2021, whereas the death proportion of ischemic stroke increased from 20.92% in 2012 to 39.96% in 2021. The average age of stroke death was delayed from 73.43 years old in 2012 to 76.52 years old in 2021 significantly (t = 18.12, p < 0.001). The percentage of stroke death at home increased from 75.23% in 2012 to 79.23% in 2021, while the percentage of stroke death at hospitals decreased from 17.89% in 2012 to 15.89% in 2021. Conclusion: The crude mortality of stroke surged, and intracerebral hemorrhage was the main death cause of all subtypes. The mortality of stroke in males and rural residents was higher than that in females and urban residents. Most stroke deaths occurred at home. Male and rural residents were crucial populations for stroke prevention and control. There should be improved medical resources in rural areas and enhanced capability of stroke diagnosis and treatment.
Measurement of Human Chorionic Gonadotrophin in Women with Gestational Trophoblastic Disease
Authors: McMahon Lesley M. , Joyce Caroline M. , Cuthill Lyndsey , Mitchell Hugh , Jabbar Imran , Sweep Fred ,   on behalf of the hCG working party of the EOTTD
Published: August 2023

Objectives: The objective of this study was to collect information on human chorionic gonadotrophin (hCG) laboratory testing and reporting in women with gestational trophoblastic disease (GTD), to assess the associated challenges, and to offer perspectives on hCG testing harmonisation. Design: Information was collected from laboratories by electronic survey (SurveyMonkey) using a questionnaire designed by members of the European Organisation for the Treatment of Trophoblastic Disease (EOTTD) hCG working party. Participants: The questionnaire was distributed by the EOTTD board to member laboratories and their associated scientists who work within the GTD field. Setting: The questionnaire was distributed and accessed via an online platform. Methods: The questionnaire consisted of 5 main sections. These included methods used for hCG testing, quality procedures, reporting of results, laboratory operational aspects, and non-GTD testing capability. In addition to reporting these survey results, examples of case scenarios which illustrate the difficulties faced by laboratories providing hCG measurement for GTD patient management were described. The benefits and challenges of using centralised versus non-centralised hCG testing were discussed alongside the utilisation of regression curves for management of GTD patients. Results: Information from the survey was collated and presented for each section and showed huge variability in responses across laboratories even for those using the same hCG testing platforms. An educational example was presented, highlighting the consequence of using inappropriate hCG assays on clinical patient management (Educational Example A), along with an example of biotin interference (Educational Example B) and an example of high-dose hook effect (Educational Example C), demonstrating the importance of knowing the limitations of hCG tests. The merits of centralised versus non-centralised hCG testing and use of hCG regression curves to aid patient management were discussed. Limitations: To ensure the survey was completed by laboratories providing hCG testing for GTD management, the questionnaire was distributed by the EOTTD board. It was assumed the EOTTD board held the correct laboratory contact, and that the questionnaire was completed by a scientist with in-depth knowledge of laboratory procedures. Conclusions: The hCG survey highlighted a lack of harmonisation of hCG testing across laboratories. Healthcare professionals involved in the management of women with GTD should be aware of this limitation. Further work is needed to ensure an appropriate, quality-assured laboratory service is available for hCG monitoring in women with GTD.
Redefining the Metabolic Syndrome in Africa: A Systematic Review between 2005 and 2022
Authors: Charles-Davies Mabel A. , Ajayi Olulope O.
Published: August 2023

Background: Metabolic syndrome (MS) is a global health challenge. Its prevalence is on the rise in the developing countries. A shift from the indigenous African diet rich in dietary fibre and micronutrients as well as sedentary lifestyle have been implicated in its aetiology. Currently, accurate definition and diagnosis of MS in Africa constitute a challenge as none of the different definitions recognized African-specific cut-off points for the different MS components. Summary: PubMed and Google databases were searched for studies between 2005 and 2022 that met the eligibility criteria of the study using expressions such as MS in Africans and components of MS in Africans. Key Messages: Observations from this review showed that the current criteria for MS diagnosis are not definite for Africans. This review article, therefore, discusses the necessity to develop African-specific criteria for MS diagnosis, which will enhance its proper diagnosis and management in Africans.
Post-Transplant Diabetes Mellitus in Renal Transplant Recipients, Single-Centre Data: Incidence, Risk Factors, and Effect on Graft Function and Mortality
Authors: Kumar Dileep , Gulzar Kashif , Alalawi Fakhriya J. , Seddik Ayman Aly , Alnour Hind , Ahmed Maseer , Najad Sima , Yousif Hussein , Railey Mohamed Hussain , Alhadari Amna Khalifa
Published: August 2023

Background: De novo post-transplant diabetes mellitus (PTDM) is a frequent complication among renal transplant recipients; it confers a high risk for graft failure and patient mortality. This single-centre study aimed to determine the incidence and risk factors of PTDM and its effects on graft outcome and mortality. Methods: In a single-centre longitudinal cohort analysis of 383 non-diabetic renal transplant follow-up recipients, outcomes were analysed through a detailed chart review. We hypothesized that different donor and recipient characters such as age, gender, and HLA mismatch would affect PTDM development in renal transplant recipients. PTDM is defined on basis of fasting plasma sugar (≥7 mmol/L or ≥126 mg/dL), random plasma sugar (≥11.1 mmol/L or ≥200 mg/dL), and glycated haemoglobin (HBA1C: >6.5% or 48 mmol/mol). We assessed PTDM incidence, risk factors, and its effect on patient mortality and graft outcome using Cox regression. Results: The mean age at the time of transplantation was 35.70 (±14.27) years, and 50.91% were male. PTDM incidence in the study period was 23.30%. Independent risk factors include older age at the time of transplantation, cyclosporine immunosuppression, cytomegalovirus, and hepatitis C virus infection. PTDM is not associated with graft dysfunction, whereas it significantly carries high mortality. Conclusion: PTDM is common among renal transplant recipients. Older age at the time of transplantation, cyclosporine immunosuppression, cytomegalovirus, and hepatitis C virus are risk factors. PTDM carries high mortality but is not associated with graft failure.
Nephrogenic Calciphylaxis Arising after Bariatric Surgery: A Case Series
Authors: Xia Joyce , Tan Alice J. , Biglione Bianca , Cucka Bethany , Ko Lauren , Nguyen Emily D. , Khoury Charbel C. , Robinson Malcolm K. , Nigwekar Sagar U. , Kroshinsky Daniela
Published: August 2023

Nephrogenic calciphylaxis is associated with multiple risk factors including long-term dialysis dependence, hyperphosphatemia, hypercalcemia, parathyroid hormone derangements, vitamin K deficiency, obesity, diabetes mellitus, warfarin use, and female sex. Bariatric surgery is known to cause altered absorption, leading to mineral and hormonal abnormalities in addition to nutritional deficiency. Prior case reports on calciphylaxis development following bariatric surgery have been published, though are limited in number. We report a case series of five bariatric patients from a single institution who developed nephrogenic calciphylaxis between 2012 and 2018. These patients had a history of bariatric surgery, and at the time of calciphylaxis diagnosis, demonstrated laboratory abnormalities associated with surgery including hypercalcemia (n = 3), hyperparathyroidism (n = 2), hypoalbuminemia (n = 5), and vitamin D deficiency (n = 5), in addition to other medication exposures such as vitamin D supplementation (n = 2), calcium supplementation (n = 4), warfarin (n = 2), and intravenous iron (n = 1). Despite the multifactorial etiology of calciphylaxis and the many risk factors present in the subjects of this case series, we submit that bariatric surgery represents an additional potential risk factor for calciphylaxis directly stemming from the adverse impact of malabsorption and overuse of therapeutic supplementation. We draw attention to this phenomenon to encourage early consideration of calciphylaxis in the differential for painful skin lesions arising after bariatric surgery as swift intervention is essential for these high-risk patients.
The Management of Acardiac Twinning: Twin Reverse Arterial Perfusion Sequence – An International Survey
Authors: Molina-Giraldo Saulo , Torres-Valencia Natalia , Johnson Anthony , Lewi Liesbeth , Ryan Greg , Sepúlveda Waldo
Published: August 2023

Introduction: The optimal approach and therapy method for the acardiac twin with a reverse arterial perfusion sequence has not yet been established. The aim of this study was to determine the clinical practice patterns among international fetal therapy units in their management of these cases. Methods: A survey was sent to fetal centers across the world via email between December 2020 and December 2021. Results: Responses were obtained from 77% contacted centers. The most frequent ultrasound variables used in the evaluation of twin reverse arterial perfusion sequence include echocardiographic assessment of the pump twin and umbilical artery Doppler waveforms in the acardiac and pump twins, in 90% and 80% of the centers, respectively. Most centers in Europe and Latin America propose an in utero intervention in all cases. Most centers in Europe and Latin America prefer interstitial laser ablation, whereas radiofrequency ablation (RFA) is preferred in North America. The earliest gestational age for an intervention is on mean 13 weeks in Europe, which is earlier than the other geographic areas (p = 0.001). Conclusions: Most centers agreed that antenatal evaluation should include echocardiography along with the UA Doppler waveform measurements, and the most frequently used interventions were interstitial laser ablation or RFA at a median between 14 and 26 weeks.
Mukoviszidose-Modulatortherapie kann zystische Bronchiektasen rückgängig machen
Authors: Middleton Peter G. , Simmonds Nicholas J.
Published: August 2023

Bronchiektasen werden oft als progressiv und irreversibel angesehen, sodass Fälle von Rückbildung oder Umkehr ein wichtiger Schritt zum Verständnis der zugrunde liegenden pathophysiologischen Mechanismen sind. Mukoviszidose (cystic fibrosis, CF), die durch pathogene Varianten des Gens CFTR (cystic fibrosis transmembrane conductance regulator) verursacht wird, ist eine Erfolgsgeschichte der personalisierten Medizin. Die jüngste Entwicklung von CFTR-Modulatortherapien hat die Behandlung revolutioniert. Innerhalb weniger Wochen wurde eine dramatische Verbesserung der Lungenfunktion, der Sputumproduktion, der Tagesform und der Lebensqualität beobachtet. Die Auswirkungen einer Langzeitbehandlung mit Elexacaftor + Tezacaftor + Ivacaftor (ETI) auf strukturelle Anomalien sind derzeit jedoch nicht bekannt. In dieser Fallserie werden 3 erwachsene Mukoviszidosepatienten beschrieben, bei denen sich die zylindrischen, varikösen und vor allem zystischen Veränderungen der Bronchiektasen nach längerer ETI-Behandlung zunehmend besserten. Dies wirft die interessante Frage nach der Reversibilität der Bronchiektasie sowie nach den Mechanismen auf, die an der Aufrechterhaltung und Progression der Bronchiektasie bei CF beteiligt sind.
Sex Steroid Hormone Receptor Content of Medial Preoptic Efferents to the Ventral Tegmental Area Is Sexually Dimorphic: Implications for Sex Differences in Mesolimbic Reward Processing
Authors: Martz Julia R. , Vasquez Adriana , Dominguez Juan M.
Published: August 2023

Introduction: The medial preoptic area (mPOA) is an important regulator of natural and drug-induced reward. However, despite the mPOA being implicated in sexually dimorphic reward responses, sex differences in medial preoptic efferents to the ventral tegmental area (VTA) have not been fully investigated. Methods: Two cohorts of male and female rats received unilateral injections of the tract-tracer Fluoro-Gold (FLG) into the VTA. Immunohistochemical staining was used to quantify co-labeled FLG-positive neurons with γ-aminobutyric acid (GABA), estrogen receptor α (ERα), and androgen receptors (AR). Results: Results revealed a pattern of VTA innervation that was comparable between males and females; more efferents emerged from the rostrocentral portions of the mPOA than caudal portions. Results also indicated that males and females had the same percentage of GABAergic mPOA-VTA projections. Differences emerged when investigating the hormone receptor profile of projections to the VTA, where females had a greater percentage of efferents expressing ERα and males had a greater percentage of efferents expressing AR, in the central portion of the mPOA. Lastly, FLG-positive cells were colocalized with GABA and ERα in cohort 1 and GABA and AR in cohort 2. The majority of AR-expressing cells colocalized with GABAergic efferents to the VTA, but only a portion of ERα-expressing cells colocalized with GABAergic efferents to the VTA. Conclusion: Results indicate that sex differences are present in the sex-steroid hormone receptor content of mPOA-VTA projections, particularly among efferents arising from the central region of the mPOA. These sexually dimorphic connections may influence a wide range of sex differences in reward responses.
Komplementäre Therapien: Bewertung der Lebensqualität bei Patienten mit Lungenkarzinom unter Bestrahlung und Therapie mit Viscum album
Authors: Voiß Petra
Published: August 2023

Background: Lung cancer (LC) is associated with high mortality and poor quality of life (QoL). The disease as well as oncological treatments such as radiation and chemotherapy with adverse effects can impair the QoL of patients. Add-on treatment with extracts of Viscum album L. (white-berry European mistletoe, VA) has been shown to be feasible and safe and to improve the QoL of cancer patients. The aim of this study was to analyze the changes in QoL of LC patients being treated with radiation according to oncological guidelines and add-on VA treatment in a real-world setting. Methods: A real-world data study was conducted using registry data. Self-reported QoL was assessed by the evaluation of the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30). Adjusted multivariate linear regression analyses were performed to analyze factors associated with changes in QoL at 12 months. Results: A total of 112 primary LC patients (all stages, 92% non-small-cell lung cancer, median age 70 (ICR: 63–75)), answered the questionnaires at first diagnosis and 12 months later. Assessment of 12 months changes in QoL revealed significant improvement of 27 points for pain (p = 0.006) and 17 points for nausea/vomiting (p = 0.005) in patients who received combined radiation and VA. In addition, significant improvements of 15 to 21 points for role (p = 0.03), physical (p = 0.02), cognitive (p = 0.04), and social functioning (p = 0.04) were observed in guideline treated patients receiving no radiation but add-on VA.
Novel Therapeutics: Can Hydrogels Work to Treat Kidney Disease?
Authors: Soranno Danielle E. , Rodell Christopher B.
Published: August 2023

Background: Hydrogels are water-swollen networks that can be made from a variety of natural and synthetic polymers. Numerous chemistries can be utilized to formulate hydrogels that are injectable, enabling facile in situ delivery of therapeutics such as cytokines or cells. Summary: Cells delivered via injectable hydrogels survive injection better than cells injected in saline or media suspension. Several materials have been used to investigate the use of injectable hydrogels to treat animal models of kidney disease. Species studied to date include mice and rats. This review summarizes the various materials, encapsulated therapeutic payloads, and preclinical models of kidney disease employed to investigate hydrogel injection. Transcutaneous measurements of glomerular filtration rate have demonstrated that delivery of hydrogels under the kidney capsule does not impair kidney function. Key Messages: Studies to date have shown the safety and efficacy of hydrogel therapies to treat kidney disease, and numerous studies have demonstrated that hydrogel therapy alone reduces inflammation and fibrosis.
Fine-Needle Aspiration of Sarcomas Metastatic to Lymph Nodes: A Cytomorphologic Study over a 10-Year Period
Authors: Saoud Carla , Lam Hansen , Ali Syed Z.
Published: August 2023

Introduction: Metastasis of sarcomas to lymph nodes is an uncommon event in its natural history. We aimed to present our experience with fine-needle aspiration (FNA) of metastatic sarcomas to lymph nodes over a 10-year period. Material and Methods: The cytopathology archives were searched for FNA of lymph nodes involved by metastatic sarcomas. Available clinicopathologic data were recorded. All slides were retrieved and reviewed. Results: Thirty-three lymph nodes, from 30 patients, with metastatic soft tissue sarcomas were identified. The lymph node metastases occurred in 16 males and 14 females (median age, 56 years). The size of the lymph nodes ranged from 1.2 to 7.5 cm (median size, 2.9 cm). The inguinal lymph nodes were the most commonly involved nodes, followed by thoracic and cervical neck nodes. The most common metastatic soft tissue sarcoma encountered was Kaposi sarcoma (n = 7, 23.3%), followed by angiosarcoma (n = 6, 20%) and rhabdomyosarcoma (n = 6, 20%). The most common site of primary soft tissue sarcoma was the head and neck (n = 8, 26.6%), followed by lower extremity (n = 7, 23.3%). The initial diagnosis of sarcoma was established in 6 cases. Seventen patients had metachronous involvement of lymph nodes, while the remaining patients had synchronous involvement. Seventen patients died of disease, and the survival after lymph node metastasis ranged from 1 to 43 months. Conclusion: FNA is an accurate and effective method in the diagnosis of metastatic sarcoma to lymph nodes. Knowledge of clinical findings and primary tumor diagnosis along with careful assessment of the cytomorphology is extremely helpful for an accurate diagnosis of metastases.
Sex Differences in the Neural Song Circuit and Its Relationship to Song Acoustic Complexity in House Wrens (Troglodytes aedon)
Authors: Krieg Cara A. , Wade Juli
Published: August 2023

The song circuit in passerine birds is an outstanding model system for understanding the relationship between brain morphology and behavior, in part due to varying degrees of sex differences in structure and function across species. House wrens (Troglodytes aedon) offer a unique opportunity to advance our understanding of this relationship. Intermediate sex differences in song rate and complexity exist in this species compared to other passerines, and, among individual females, song complexity varies dramatically. Acoustic complexity in wild house wrens was quantified using a new machine learning approach. Volume, cell number, cell density, and neuron soma size were then measured for three song circuit regions, Area X, HVC (used as a proper name), and the robust nucleus of the arcopallium (RA), and one control region, the nucleus rotundus (Rt). For each song control area, males had a larger volume with more cells, larger somas, and lower cell density. Male songs had greater acoustic complexity than female songs, but these distributions overlapped. In females, increased acoustic complexity was correlated with larger volumes of and more cells in Area X and RA, as well as larger soma size in RA. In males, song complexity was unrelated to morphology, although our methods may underestimate male song complexity. This is the first study to identify song control regions in house wrens and one of few examining individual variation in both sexes. Parallels between morphology and the striking variability in female song in this species provide a new model for understanding relationships between neural structure and function.
Risk of Chronic Kidney Disease in Hospitalized Patients with Hidradenitis Suppurativa
Authors: Almuhanna Nouf , Tobe Sheldon W. , Alhusayen Raed
Published: August 2023

Background: Hidradenitis suppurativa (HS) is associated with several comorbidities such as diabetes mellitus and cardiovascular diseases. These comorbidities are also risk factors for chronic kidney disease (CKD), yet little is known about the risk of CKD in HS patients. Objectives: The objective was to study the prevalence of CKD in HS patients. Methods: Cross-sectional population-based study using the United States National Inpatient Sample database between January 1, 2002 and December 31, 2012 was performed. Results: We identified 23,767 hospital admissions for HS patients and 95,068 admissions for age- and gender-matched controls. The prevalence of CKD in HS patients was 6.3% (1,497/23,767) compared to non-HS controls which was 4.3% (4,052/95,068). The association of CKD was strongest in HS patients, who were ≥60 years old, 16.9% (475/2,811), male 7.3% (695/9,556), obese 7.8% (407/5,209), diabetic 12.5% (890/7,105), hyperlipidemic 13.3% (416/3,126), and had cardiovascular diseases 12.5% (631/5,045). The crude odds ratio of CKD in HS patients was 1.5 (95% CI: 1.420–1.605) compared to non-HS patients. The association remained significant after adjusting for important covariates with adjusted odds ratio of CKD in HS patients of 1.1 (95% CI: 1.014–1.176) compared to non-HS patients. Conclusions: Our findings show that there is a possible association of HS with CKD. Any signs of CKD should be assessed by a nephrologist as early diagnosis can hopefully prevent further progression.
From Nose to Lumbar Spinal Cord – Reduced Sperm Numbers Occur by Olfactory Bulbectomy-Related Onuf’s Nucleus Degeneration: New Experimental Evidence for Kallmann Syndrome
Authors: Yolas Coskun , Kanat Ayhan , Zeynal Mete , Sahin Mehmet H. , Karadag Mehmet K. , Keles Osman N. , Akca Nezih , Dil Eyup , Aydin Mehmet D. , Gundogdu Omer Lutfi
Published: August 2023

Introduction: Olfaction and its relation to human health is an area of growing interest. Although olfaction disorders have been considered a part of Kallmann syndrome, the role of olfactory dysfunction on spermatogenesis has not been studied yet. We studied if olfactory bulbectomy (OBX) causes dysfunction in spermatogenesis as a result of Onuf’s nucleus damage. Methods: Twenty-eight male rats were divided into three groups: six as the control (G-1; n = 6), six as the only frontal burr hole applied animals SHAM (G-2; n = 6), and 16 as the study group (G-3; n = 16) in which OBX was performed. The animals were followed for 2 months. After the decapitation of the animals, olfactory bulb (OB) volumes (mm3), the neuron density of the Onuf’s nucleus (n/mm3), and sperm density (n/mm3) were estimated stereologically and analyzed. Results: OB volumes (mm3), degenerated neuron density of Onuf’s nucleus (n/mm3), and sperm numbers of control, SHAM, and study groups were estimated as: 4 ± 0.5; 6 ± 2 and 103.245 ± 10.841 in G-1; 3.5 ± 0.7; 14 ± 4 and 96.891 ± 9.569 in G-2; and 1.3 ± 0.3; 91 ± 17 and 73.561 ± 6.324 in G-3. The statistical results of degenerated neuron density of Onuf’s nucleus and sperm numbers between groups are p < 0.005 for G-1/G-2; p < 0.0005 for G-2/G-3; and p < 0.00001 for G-1/G-3. Discussion: This study first time indicates that Onuf’s nucleus degeneration secondary to OBX seems to be responsible for reduced sperm numbers.
Finerenone in Patients with Chronic Kidney Disease and Type 2 Diabetes: The FIDELIO-DKD Subgroup from China
Authors: Zhang Haitao , Xie Jingyuan , Hao Chuanming , Li Xuemei , Zhu Dalong , Zheng Hongguang , Xu Xudong , Mo Zhaohui , Lu Weiping , Lu Yibing , Wu Chaoqing , Tong Nanwei , Wang Li , Liu Zhihong
Published: August 2023

Background: This prespecified subgroup analysis of the FIDELIO-DKD trial aimed to evaluate the efficacy and safety of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in China. Methods: 372 participants were recruited from 67 centers in China and randomized 1:1 to oral finerenone or placebo with standard therapy for T2DM. The primary composite outcome included kidney failure, sustained decrease of estimated glomerular filtration rate ≥40% from baseline over at least 4 weeks, or renal death. The key secondary composite outcome included death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results: After a median follow-up of 30 months, the finerenone group showed a relative risk reduction (RRR) of 41% (hazard ratio [HR] = 0.59, 95% confidence interval [CI], 0.39–0.88; p = 0.009) for the primary composite outcome compared with placebo, consistent across its components with treatment benefits with finerenone. Based on an absolute between-group difference of 12.2% after 30 months, the number of patients who needed to be treated with finerenone to prevent one primary outcome event was eight (95% CI: 4–84). For the key secondary composite outcome, the finerenone group showed a RRR of 25% (HR = 0.75, 95% CI, 0.38–1.48; p = 0.408). Adverse events were similar between the two groups. The effects of finerenone on blood pressure were modest. No gynecomastia events were reported in the study. Hyperkalemia leading to discontinuation occurred in eight (4.3%) and two (1.1%) participants in the finerenone and control groups, respectively. The incidence of acute kidney injury was comparable between the two groups (1.6% vs. 1.6%). Conclusions: Finerenone resulted in lower risks of CKD progression than placebo and a balanced safety profile in Chinese patients with CKD and T2DM.
Protective Effect of Vaccinium myrtillus Extract on X-Ray Irradiation-Induced Retinal Toxicity via eNOS and 8-OHdG expression
Authors: Fındık Hüseyin , Aslan Mehmet Gökhan , Okutucu Murat , Yılmaz Adnan , Tümkaya Levent , Mercantepe Tolga , Akyıldız Kerimali , Uzun Feyzahan
Published: August 2023

Every year, hundreds of thousands of cancer patients receive radiotherapy treatment. Oxidative stress is observed in healthy tissues due to irradiation exposure. The present study is the first to address the effects of Vaccinium myrtillus (whortleberry, WB) against the effects of X-ray irradiation on retinal tissue. Twenty-four Sprague-Dawley rats were randomly allocated into 4 groups: (1) control group: rats without any treatment, (2) X-ray irradiation group: 8 Gray (Gy) RT for 2 days, (3) 100 mg WB extract + X-ray irradiation group: 8 Gy irradiation for 2 days and followed by intraperitoneal (IP) WB extract (100 mg/kg) supplementation for 10 days, (4) 200 mg WB extract + X-ray irradiation group: 8 Gy irradiation for 2 days and followed by IP WB extract (200 mg/kg) supplementation for 10 days. Eyes were enucleated on the 10th day after RT for histopathological, immunohistochemical (8-hydroxy-2′-deoxyguanosine [8-OHdG], endothelial nitric oxide synthase [eNOS]), and biochemical analyses (glutathione peroxidase [GSH], and malondialdehyde [MDA]). The GSH levels significantly decreased and MDA levels and 8-OHdG staining increased after X-ray irradiation compared to the control group. Combined X-ray irradiation + WB treatment significantly increased GSH levels and significantly decreased MDA production and 8-OHdG staining. However, eNOS staining was not affected in any of the groups. Besides, X-ray irradiation significantly increased cell losses and edematous areas. The WB significantly reversed the cellular damage in ganglion cells, inner nuclear, and outer nuclear layers in quantitative analyses. The X-ray irradiation caused significant retinal impairment, and additional WB therapy provided protective effects against radiation-induced retinopathy. These results may suggest WB extract as an adjuvant therapy to reverse retinal impairments after X-ray irradiation.