bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences and correlations of biochemical index levels in patients with bipolar disorder and major depressive disorder during a stable period
Authors: Tan Yukang , Zhang Chunguo , Tang Chaohua , Li Zhijian , Chen Wensheng , Jing Huan , Liang Wenting , Li Xiaoling , Xie Guojun , Liang Jiaquan , Guo Huagui
Published: June 2023

The differences and correlation of biochemical indexes between bipolar disorder (BPD) and major depressive disorder (MDD) in stable stage were analyzed and discussed. Patients diagnosed with BPD and MDD in the Third People’s Hospital of Foshan from January 2019 to December 2021 were selected as the research subjects, with 200 cases in each. Fasting serum was collected from patients and then detected regarding TC, TG, high-density lipoprotein, low-density lipoprotein (LDL), aspartate aminotransferase, lactic dehydrogenase, creatine kinase, creatine kinase-MB, urea, creatinine, uric acid, alanine aminotransferase, glucose (GLU), hemoglobin A1c, prolactin, high-sensitivity C-reactive protein, homocysteine. The results showed that the mean age and serum LDL, GLU, and HbAc1 levels of the MDD group were significantly higher than those of the BPD group (P < .05), while there was no significant difference in other indexes (P > .05). The prevalence of BPD was significantly negatively correlated with patient age (r = −0.164, P = .020), LDL (r = −0.150, P = .034), GLU (r = −0.140, P = .048), and HbAc1 (r = −0.215, P = .002) (P < .05). There were no significant differences in serum Hcy and high-sensitivity C-reactive protein levels between the BPD and MDD groups. The age, fasting blood glucose, glycosylated hemoglobin, and LDL of BPD patients were negatively correlated with their incidence.
Safety and efficacy of pediatric sedation protocol for diagnostic examination in a pediatric emergency room: A retrospective study
Authors: Kim Da Hyun , Chun Min Kyo , Lee Jeong-Yong , Lee Jong Seung , Ryu Jeong-Min , Choi Seung Jun , Park Jun Sung
Published: June 2023

Pediatric patients undergoing diagnostic tests in the pediatric emergency room are frequently sedated. Although efforts are made to prevent adverse events, no sedation protocol has specified the optimal regimen, dosage, and interval of medication to prevent adverse events. This study analyzed the safety and efficacy of sequential pediatric sedation protocols for pediatric patients undergoing diagnostic tests in the pediatric emergency room of a single tertiary medical center. The medical records of patients aged < 18 years who visited the pediatric emergency room of Seoul Asan Medical Center between January and December 2019 for diagnostic testing were retrospectively reviewed. Sedation protocols consisted of 50 mg/kg and 25 mg/kg chloral hydrate, 0.1 mg/kg and 0.1 mg/kg midazolam, and 1 mg/kg and 0.5 to 1 mg/kg ketamine, administered sequentially at intervals of 30, 20, 10, 10, and 10 minutes, respectively. Patients were assessed prior to sedation, and adverse events were investigated. Of the 289 included patients, 20 (6.9%) experienced adverse events, none serious, and nine (3.1%) failed to reach the depth of sedation required to complete the test. The regimen (P = .622) and dosage (P = .777) of the sedatives were unrelated to the occurrence of adverse events when sedation was performed according to protocol. The sedation protocol used in these patients, consisting of sequential administration of minimum dosages, achieved a sufficient depth of sedation with relatively few adverse events, indicating that this protocol can be used safely and effectively for painless sedation in pediatric patients undergoing diagnostic testing.
Ichthyosis: presentation and management
Authors: Butala Sneha , Mazereeuw-Hautier Juliette , Paller Amy S.
Published: June 2023

Purpose of review

This review focuses on the presentation and management of ichthyoses and highlights recent advances in treatment that hold promise for better targeted therapy.

Recent findings

The ichthyoses are a group of rare genetic diseases with a wide phenotypic spectrum, characterized most often by generalized hyperkeratosis and scaling with variable erythema. The highly visible scaling and frequent itch contribute to decreased quality of life. Management for ichthyosis focuses on symptomatic relief and scale reduction with emollients, keratolytics, and retinoids. Recent advances in immune profiling and genotype-phenotype mapping have increased understanding of ichthyosis and shifted focus to pathogenesis-based targeted therapies with emerging biologics, small molecular inhibitors, and gene therapy.

This article discusses clinical assessment and genotyping to make the diagnosis of specific forms of ichthyosis, provides guidance for management, and reviews new treatment options with systemic agents.
Stroke and kidney transplantation
Authors: Abreo Adrian P. , Kataria Deepak , Amrutkar Chaitanya , Singh Ayush , Samaniego Millie , Singh Neeraj
Published: June 2023

Purpose of review

This review will focus on the epidemiological data, risk factors, and management of stroke before and after kidney transplant. Stroke is highly prevalent in waitlisted patients as well as kidney transplant recipients and is associated with impaired transplant outcomes. Multiple traditional, nontraditional, and transplanted risk factors increase the risk of stroke.

Recent findings

Although the risk of stroke is reduced after kidney transplantation compared with remaining on dialysis, the morbidity and mortality from stroke after transplantation remain significant.

Early screening for risk factors before and after a kidney transplant and following the Kidney Disease Improving Global Outcomes (KDIGO) management guidelines could minimize the incidence of stroke and transplant outcomes.
Exome Sequencing Implicates DGKZ, ESRRA, and GXYLT1 for Modulating Granuloma Formation in Crohn Disease
Authors: Harris R. Alan , Bush Allyson H. , Eagar Todd N. , Qian Justin , Greenwood Michael P. , Opekun Antone R. , Baldassano Robert , Guthery Stephen L. , Noe Joshua D. , Otley Anthony , Rosh Joel R. , Kugathasan Subra , Kellermayer Richard
Published: June 2023

Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases. PLINK (a tool set for whole-genome association and population-based linkage analyses) analysis was used to identify single nucleotide polymorphisms (SNPs) differentiating between groups, and subgroup allele frequencies were also compared to a public genomic database (gnomAD). The Combined Annotation Dependent Depletion scoring tool was used to predict deleteriousness of SNPs. Human leukocyte antigen (HLA) haplotype findings were compared to a control group (n = 8496). PLINK-based analysis between GCD and NGCD groups did not find consistently significant hits. gnomAD control comparisons, however, showed consistent subgroup associations with DGKZ, ESRRA, and GXYLT1, genes that have been implicated in mammalian granulomatous inflammation. Our findings may guide future research and precision medicine.
Exploring Audio Recording in Terminally Ill Patients Receiving Hospice Care
Authors: Halton-Hernandez Emilia , Abrams Robert , Cooney Geraldine , Ali Khalid
Published: June 2023

Stories for Life is a UK charity that provides a free and confidential service for terminally ill patients to audio record their “life story.” Patients are given a copy of the recording and, if they wish, can then pass a copy on to their family/friends. This study explored how a group of terminally ill patients, receiving hospice care, experienced the process of making a voice recording of their biographies. Interviews were conducted with 5 terminally ill patients and 1 family member. Study participants found that talking to a trained volunteer provided a neutral, nonjudgmental interviewer. Patients reported a feeling of catharsis while telling their story as well as being able to reflect on significant life events. However, it was challenging to convey difficult emotions while also being mindful of protecting family who may listen to the recording. Although there was some uncertainty about how the recording would be perceived by listeners, leaving a voice-recorded life account was felt to be beneficial for immediate family members, as well as maintaining a meaningful connection with future generations. Overall, recording an audio biography in terminal illness can allow patients a space for reflection and a meaningful connection with their families.
Longitudinal Effects of Sex, Aging, and Multiple Sclerosis Diagnosis on Function
Authors: Harrison Tracie C. , Blozis Shelley A. , Stuifbergen Alexa K. , Becker Heather
Published: June 2023

Background

A gap in research about the trajectories of function among men and women aging with functional limitations because of multiple sclerosis (MS) hinders ability to plan for future needs.

Objectives

Using a biopsychosocial model, we characterize how men and women with MS report changes over time in their function and test how person-level differences in age, diagnosis duration, and sex influence perceived function.

Methods

A longitudinal study with multiple waves of surveys was used to collect data on participant perceptions of function, as well as demographic and contextual variables. Self-reported functional limitation was measured over a decade. The study participants were community residing with physician-diagnosed MS.

Results

The people with MS had a diagnosis duration of about 13 years and were around 51 years of age, on average, at the start of the study. They were primarily women and non-Hispanic White. We analyzed the data using mixed-effects models. Subject-specific, functional limitation trajectories were described best with a quadratic growth model. Relative to men, women reported lower functional limitation and greater between-person variation and rates of acceleration in functional limitation scores.

Discussion

Results suggest function progressed through two pathways for over a decade, particularly closer to diagnoses. Variability in trajectories between individuals based on sex and years since diagnosis of disease indicates that men and women with MS may experience perceptions of their function with age differently. This has implications for clinician advice to men and women with MS.
Case Comparison of Preterm Infant Stability During Packed Red Blood Cell Transfusions
Authors: Everhart Kayla C. , Donevant Sarah B. , Iskersky Victor N. , Wirth Michael D. , Dail Robin B.
Published: June 2023

Background

Very preterm infants (less than 32 weeks gestational age) experience acute morbidity during their stay in a neonatal intensive care unit. Because of their prematurity and frequent laboratory testing, they experience anemia, requiring correction with packed red blood cell (PRBC) transfusion(s). PRBC transfusions have been linked to neonatal morbidity, such as necrotizing enterocolitis, but never signs and symptoms of physiological stability.

Objective

The secondary data analysis aimed to examine very preterm infants’ physiological stability before, during, and after PRBC transfusions.

Methods

A within-case, mixed-methods design was used in a secondary data analysis for 16 transfusion cases from 13 very preterm infants.

Results

The findings showed very preterm infants with physiological variables falling within defined limits based on gestational age during the transfusion. Two contrasting case exemplars will be presented.

Discussion

PRBC transfusions are necessary and prevent morbidity in very preterm infants. Observing instability during transfusions and prospectively studying hypothermia, cardiac instability, and thermal gradients is essential to design interventions to decrease morbidity associated with PRBC transfusions.
Center Volume and Survival Relationship for Neonates With Congenital Diaphragmatic Hernia Treated With Extracorporeal Life Support
Authors: Martino Alice M. , Nguyen Danh V. , Delaplain Patrick T. , Dinh Peter , Jancelewicz Tim , Harting Matthew T. , Yu Peter T. , Di Nardo Matteo , Gowda Sharada , Goodman Laura F. , Yu Yangyang , Guner Yigit S.
Published: June 2023

OBJECTIVES:

Literature is emerging regarding the role of center volume as an independent variable contributing to improved outcomes. A higher volume of index procedures may be associated with decreased morbidity and mortality. This association has not been examined for the subgroup of infants with congenital diaphragmatic hernia (CDH) receiving extracorporeal life support (ECLS). Our study aims to examine the risk-adjusted association between center volume and outcomes in CDH-ECLS neonates, hypothesizing that higher center volume confers a survival advantage.

DESIGN:

Multicenter, retrospective comparative study using the Extracorporeal Life Support Organization database.

SETTING:

One hundred twenty international pediatric centers.

PATIENTS:

Neonates with CDH managed with ECLS from 2000 to 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The cohort included 4,985 neonates with a mortality rate of 50.6%. For the 120 centers studied, mean center volume was 42.4 ± 34.6 CDH ECLS cases over the 20-year study period. In an adjusted model, higher ECLS volume was associated with lower odds of mortality: odds ratio (OR) 0.995 (95% CI, 0.992–0.999; p = 0.014). For an increase in one sd in volume, that is, 1.75 cases annually, the OR for mortality was lower by 16.7%. Volume was examined as a categorical exposure variable where low-volume centers (fewer than 2 cases/yr) were associated with 54% higher odds of mortality (OR, 1.54; 95% CI, 1.03–2.29) compared with high-volume centers. On-ECLS complications (mechanical, neurologic, cardiac, hematologic metabolic, and renal) were not associated with volume. The likelihood of infectious complications was higher for low- (OR, 1.90; 95% CI, 1.06–3.40) and medium-volume (OR, 1.87; 95% CI, 1.03–3.39) compared with high-volume centers.

CONCLUSIONS:

In this study, a survival advantage directly proportional to center volume was observed for CDH patients managed with ECLS. There was no significant difference in most complication rates. Future studies should aim to identify factors contributing to the higher mortality and morbidity observed at low-volume centers.
Association of marijuana, tobacco and alcohol use with estimated glomerular filtration rate in women living with HIV and women without HIV
Authors: Fisher Molly C. , Hoover Donald R. , Shi Qiuhu , Sharma Anjali , Estrella Michelle M. , Adimora Adaora , Alcaide Maria , Collins Lauren F. , French Audrey , Gao Wei , Koletar Susan L. , Mcfarlane Samy I. , Mckay Heather , Dionne Jodie A. , Palella Frank , Sarkar Sudipa , Spence Amanda , Witt Mallory D. , Ross Michael J.
Published: June 2023

Objective:

Marijuana, tobacco and alcohol use are prevalent among people living with HIV and may adversely affect kidney function in this population. We determined the association of use of these substances with estimated glomerular filtration rate (eGFR) among women living with HIV (WLWH) and women without HIV.

Design:

We undertook a repeated measures study of 1043 WLWH and 469 women without HIV within the United States Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-seropositive and HIV-seronegative women.

Methods:

We quantified substance exposures using semi-annual questionnaires. Using pooled eGFR data from 2009–2019, we used linear regression models with multivariable generalized estimating equations to ascertain associations between current and cumulative substance use exposures with eGFR, adjusting for sociodemographics, chronic kidney disease risk factors and HIV-related factors.

Results:

Marijuana use of 1–14 days/month versus 0 days/month was associated with 3.34 mL/min/1.73m2 (95% CI -6.63, -0.06) lower eGFR and marijuana use of >0.02–1.6 marijuana-years versus 0–0.2 marijuana-years was associated with 3.61 mL/min/1.73m2 (95% CI -5.97, -1.24) lower eGFR. Tobacco use was not independently associated with eGFR. Alcohol use of >7 drinks/week versus 0 drinks/week was associated with 5.41 mL/min/1.73m2 (95% CI 2.34, 8.48) higher eGFR and alcohol use of >0.7–4.27 drink-years and >4.27 drink-years versus 0–0.7 drink-years were associated with 2.85 mL/min/1.73m2 (95% CI 0.55, 5.15) and 2.26 mL/min/1.73m2 (95% CI 0.33, 4.20) higher eGFR, respectively.

Conclusion:

Among a large cohort of WLWH and women without HIV, marijuana use was associated with a lower eGFR while alcohol use was associated with a higher eGFR.
Sex modifies the risk of HIV-associated obstructive lung disease in ugandans post-pneumonia
Authors: Abelman Rebecca A. , Fitzpatrick Jessica , Zawedde Josephine , Sanyu Ingvar , Byanyima Patrick , Kaswabuli Sylvia , Musisi Emmanuel , Hsieh Jenny , Gardner Kendall , Zhang Michelle , Byanova Katerina L. , Sessolo Abdul , Hunt Peter W. , Lalitha Rejani , Davis J. Lucian , Crothers Kristina , Worodria William , Huang Laurence
Published: June 2023

Objectives:

Spirometric abnormalities are frequent and obstructive lung disease (OLD) is a common comorbidity among people with HIV (PWH). HIV increases the risk of many comorbidities to a greater degree in women than in men. Few studies have evaluated whether sex modifies the HIV-associated risk of OLD.

Design and Methods:

To evaluate the associations between sex and HIV with abnormal lung function, women and men with and without HIV underwent spirometric testing after completing therapy for pneumonia, including tuberculosis (TB), in Kampala, Uganda. OLD was defined as a post-bronchodilator forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) ratio <0.70. Associations between sex, HIV, and lung function were evaluated using multivariable regression models including sex-by-HIV interaction terms after adjusting for age, body mass index (BMI), smoking status, and TB status.

Results:

Among 348 participants, 147 (42%) were women and 135 (39%) were HIV positive. Sixteen (11%) women and 23 men (11%) had OLD. The HIV-sex interaction was significant for obstructive lung disease (p = 0.04). In the adjusted stratified analysis, women with HIV had 3.44 (95% CI 1.11, 12.0; p = 0.04) increased odds of having OLD compared to men with HIV. Women without HIV did not have increased odds of having OLD compared to men without HIV.

Conclusions:

HIV appears to increase the risk of OLD to a greater degree in women than in men in an urban Ugandan setting. The mechanistic explanation for this interaction by sex remains unclear and warrants further study.
HIV-positive Ukrainian refugees in the Czech Republic: a retrospective, observational study
Authors: Massmann Ricardo , Groh Tomáš , Jilich David , Bartková Daniela , Bartovská Zofia , Chmelař Josef , Chrdle Aleš , Dlouhý Pavel , Cimrman Štěpán , da Silva Simona Guimaraes , Kapla Jaroslav , Kubiska Miroslav , Snopková Svatava , Svačinka Radek , Zlámal Milan , Samsonová Olena , Sedláček Dalibor
Published: June 2023

Objective:

Over 480 000 Ukrainian refugees have arrived in the Czech Republic since the Russian invasion of Ukraine in 2022, including over 500 people with HIV. This study describes the demographics, characteristics, and management of Ukrainian refugees with HIV in the Czech Republic.

Design:

Retrospective, observational, non-interventional study.

Methods:

Ukrainian nationals registering at HIV centers in the Czech Republic with war refugee status were included. Data were collected from medical records between 1 March and 31 July 2022. The study was registered with the Czech State Institute for Drug Control, ID number 2301200000.

Results:

482 patients were included in the study. Most patients were female (69.5%; n = 335/482) with well-controlled HIV. The median [interquartile range] CD4+ cell count was 597 [397] cells/mm3 of blood, and 79.3% (n = 361/455) of patients had HIV RNA <40 copies/ml. Coinfections of hepatitis C virus, hepatitis B virus, and/or tuberculosis were reported for 17.4% (n = 78/449), 9% (n = 40/446) and 1.3% (n = 6/446) of patients, respectively. In Ukraine, 85.7% (n = 384/448) of patients had been receiving an integrase strand transfer inhibitor-based regimen and most (69.7%; n = 310/445) did not switch therapy upon arrival in the Czech Republic.

Conclusion:

Migration from Ukraine is changing the characteristics of HIV epidemiology in the Czech Republic. Ukrainian refugees with HIV have been provided with a high standard of medical care in the Czech Republic. Improved coordination between medical services within the Czech Republic and between countries in the European Union is necessary to optimize patient care.
68Ga-FAPI-04 PET/CT in Selected Breast Cancer Patients With Low FDG Affinity
Authors: Alçın Göksel , Arslan Esra , Aksoy Tamer , Cin Merve , Erol Fenercioğlu Özge , Beyhan Ediz , Ergül Nurhan , Çermik Tevfik Fikret
Published: June 2023

Purpose

In this prospective study, PET findings of18F-FDG PET/CT in breast cancer staging were compared with68Ga–FAP inhibitor (FAPI) 04 PET/CT findings in selected cases with relatively low18F-FDG uptake in the primary tumor or with suspected nodal or distant metastases.

Patients and Methods

Twenty-four women with a median age of 45 years (range, 36–67 years) who underwent initial staging18F-FDG PET/CT for breast cancer underwent68Ga-FAPI-04 PET/CT imaging within the same week. SUVmaxand quantities of primary tumors and locoregional and distant metastatic lesions were recorded from both images, and these data were compared statistically.

Results

The histological subtypes of primary tumors were 11 invasive lobular, 8 invasive ductal, and 5 mucinous subtypes. More intense68Ga-FAPI-04 uptake (mean, 17.1 ± 7.9; 7.4–38.5) was detected in all primary tumoral lesions compared with18F-FDG (mean, 6.3 ± 3.9; 1.5–20.5) (P= <0.001,Z= 4.107). Additional lesions showing68Ga-FAPI-04 uptake in the breast were detected in 29.2% (n = 7) of patients. In 8.3% (n = 2) of the patients, the primary lesion showed only68Ga-FAPI-04 uptake. In68Ga-FAPI-04 PET/CT, 25% (n = 6) of the patients showed more lymph node involvement and more intense uptake in the ipsilateral axilla. In addition, infraclavicular (level 3) lymph nodes in 4 patients (16.7%), supraclavicular lymph nodes in 1 patient, and internal mammary lymph nodes in 1 patient were detected only on68Ga-FAPI-04 PET/CT. In a patient with lung and bone metastases,68Ga-FAPI-04 uptake was higher, and the lung nodule showed only68Ga-FAPI-04 uptake.

Conclusions

In selected low-FDG-affinity breast cancer patients,68Ga-FAPI-04 PET/CT showed the primary tumor with higher sensitivity and higher SUVmaxvalues compared with18F-FDG PET/CT. In addition, it is believed that this method may contribute to the management of patients' treatment by increasing the nodal stage.
Omental Hibernoma Revealed by 18F-FDG PET/CT
Authors: Qi Jin , Kurian Elizabeth , Öz Orhan K.
Published: June 2023

Hibernomas are “pseudolipomas” originating from remnants of fetal brown adipose tissue. These rare benign tumors may occur throughout the body but most commonly in the thigh, shoulder, back, and neck, and are rarely found in the abdominal cavity, retroperitoneum, breast, bones, scrotum, and perirectum. We present a case of a 58-year-old woman with a known mediastinal mass, who was incidentally found to have a very FDG-avid fat-containing lesion in the omentum abutting the stomach. Subsequent endoscopic ultrasound-guided fine-needle aspiration confirmed hibernoma. The review of the literature shows the location is very unusual.
Evaluation of Microvascular Autologous Breast Reconstruction in Patients Older Than 60 Years
Authors: Parmeshwar Nisha , Barnes Laura L. , Dugan Catherine L. , Patterson Anne K. , Lem Melinda , Piper Merisa
Published: June 2023

Background

While free-flap breast reconstruction becomes more common, it is still approached with caution in older patients. Outcomes in the elderly population have not been well characterized, especially with regard to donor-site sequalae. This study compares microvascular autologous breast reconstruction outcomes in patients older and younger 60 years.

Methods

A single-institution retrospective review was performed for microvascular autologous breast reconstruction from January 2004 through January 2021. Demographic, intraoperative, and postoperative variables, including breast flap and donor-site complications, were evaluated.

Results

Five hundred forty-five breast free flaps were identified, of which 478 (87.8%) were performed on patients younger than 60 years (mean, 46.2 years) and 67 (12.2%) older than 60 years (mean, 64.8 years; P = 0.000). Hyperlipidemia was significantly higher in older patients (19.4% vs 9.6%, P = 0.016). Mean operative time was 46.3 minutes faster in the older cohort (P = 0.030). There were no significant differences in free-flap loss, venous congestion, takeback, hematoma, seroma, wound healing, or infection. Interestingly, there were significantly more total breast flap complications (28.5% vs 16.4%, P = 0.038) and higher rates of fat necrosis (9.6% vs 1.5%, P = 0.026) in the younger cohort. Significantly more abdominal donor-site complications (43.3% vs 21.3%, P = 0.000) were seen in the older people, with increased wound breakdown (P = 0.000) and any return to the operating room (20.9% vs 9.8%, P = 0.007). Older patients were also significantly more likely to require surgical correction of an abdominal bulge or hernia (10.4% vs 4%, P = 0.020). The mean follow-up was 1.8 years.

Conclusions

Our data showed no worsening of individual breast flap outcomes in the older people. However, there were significantly more abdominal complications including surgical correction of abdominal bulge and hernia. This may be related to the inherent qualities of tissue aging and should be taken into consideration for flap selection. These results support autologous breast reconstruction in patients older than 60 years, but patients should be counseled regarding potentially increased abdominal donor-site sequelae.
Association between right heart catheterization hemodynamics and glycosylated hemoglobin levels in adults with heart failure with reduced ejection fraction
Authors: Del Rio-Pertuz Gaspar , Morataya Cristina , Parmar Kanak , Elharabi Zeyad , Davis Daniel , Abohelwa Mostafa , Ochoa Ozman , Tran Alison , Nugent Kenneth , Paniagua David , Argueta-Sosa Erwin
Published: June 2023

Background

This study hypothesized that elevated glycosylated hemoglobin (HbA1c) levels are associated with abnormal right heart catheterization (RHC) hemodynamic parameters in patients with heart failure with reduced ejection fraction (HFrEF) and no prior diagnosis of diabetes.

Methods

Retrospective cohort study of adult patients with HFrEF and no prior diagnosis of diabetes who underwent RHC and had HbA1c levels measured 30 days before or after the RHC. This study excluded patients who had received blood transfusions within 90 days prior to HbA1c measurement and patients with known diabetes. Univariate and multivariate regression analyses adjusted for age, sex, and BMI were used to test for an association between RHC hemodynamic parameters and HbA1c levels.

Results

A total of 136 patients were included with a mean age of 55 ± 15 years and mean HbA1c was 5.99 ± 0.64%. Unadjusted univariate models showed that HbA1c is significantly associated with cardiac index (CI) by the Fick method and thermodilution, right atrial pressure (RAP), and mean pulmonary arterial pressure (MPAP). After multivariate analysis, for every one unit increase in HbA1c, there was a 0.19 and 0.26 L/min/m2 decrease in expected CI by thermodilution and by the Fick method (P = 0.03 and P < 0.01), respectively. For every one unit increase in HbA1c, there was a 2.39 mmHg increase in expected RAP (P = 0.01).

Conclusion

Elevated HbA1c levels measured within 30 days before or after the index RHC in patients with a left ventricular ejection fraction <40% were associated with congestive hemodynamic parameters.
First episode psychosis and weight gain a longitudinal perspective in Cheshire UK: a comparison between individuals with nonaffective versus affective psychosis
Authors: Heald Adrian H. , Stedman Mike , Daly Chris , Warner-Levy John Julian , Livingston Mark , Hussain Lamiece , Anderson Simon
Published: June 2023

Introduction

Early weight gain following initiation of antipsychotic treatment predicts longer-term weight gain, with attendant long-term consequences including premature cardiovascular events/death. An important question is whether there is a difference in weight change over time between people with affective versus nonaffective psychosis. Here we describe the results of a real-world analysis of the BMI change in the months postdiagnosis with affective versus nonaffective psychosis.

Methods

We undertook an anonymised search across one Primary Care Network in Cheshire, UK with a total population of 32 301 individuals. We reviewed the health records of anyone who had been diagnosed over a 10-year period between June 2012 and June 2022 for the first time with first episode nonaffective psychosis versus psychosis associated with depression or bipolar affective disorder (affective psychosis).

Results

The overall % change in BMI was +8% in nonaffective psychosis individuals and +4% in those with a diagnosis of affective psychosis – however, the distribution was markedly skewed for nonaffective psychosis patients. Using caseness as >30% increase in BMI; affective = 4% cases and nonaffective = 13% cases, there was a three-fold difference in terms of increase in BMI. In regression analysis, the r
2 linking the initial BMI to % change in BMI was 0.13 for nonaffective psychosis and 0.14 for affective psychosis.

Conclusion

The differences observed here in the distribution of weight change over time between individuals with affective versus nonaffective psychosis may relate to underlying constitutional differences. The phenotypic and genetic factors underlying this difference remain to be defined.
Leadership and Impostor Syndrome in Surgery
Authors: Iwai Yoshiko , Yu Alice Yunzi L , Thomas Samantha M , Fayanju Oluseyi A , Sudan Ranjan , Bynum Debra L , Fayanju Oluwadamilola M
Published: June 2023

Background:

Impostor syndrome is an internalized sense of incompetence and not belonging. We examined associations between impostor syndrome and holding leadership positions in medicine.

Study Design:

A cross-sectional survey was distributed to US physicians from 6/2021-12/2021 through medical schools and professional organizations. Differences were tested with the chi-square test and t-test for categorical and continuous variables, respectively. Logistic regression was used to identify factors associated with holding leadership positions and experiencing impostor syndrome.

Results:

2183 attending and retired physicians were included in the analytic cohort; 1471 (67.4%) were in leadership roles and 712 (32.6%) were not. After adjustment, male physicians were more likely than women to hold leadership positions (OR=1.4, 95% CI 1.16-1.69; p<0.001). Non-US citizens (permanent resident or visa holder) were less likely to hold leadership positions than US citizens (OR=0.3, 95% CI 0.16-0.55; p<0.001). Having a leadership position was associated with lower odds of impostor syndrome (OR=0.54, 95% CI 0.43-0.68; p<0.001). Female surgeons were more likely to report impostor syndrome compared to male surgeons (90.0% vs 67.7%; p<0.001), an association that persisted even when female surgeons held leadership roles. Similar trends were appreciated for female and male non-surgeons. Impostor syndrome rates did not differ by race/ethnicity, including among those underrepresented in medicine, even after adjustment for gender and leadership role.

Conclusions:

Female physicians were more likely to experience impostor syndrome than men, regardless of specialty or leadership role. While several identity-based gaps persist in leadership, impostor syndrome among racially minoritized groups may not be a significant contributor.
Target temperature management and post-extracorporeal cardiopulmonary resuscitation outcome: A post hoc analysis of the SAVE-J II Study
Authors: Kanda Jun , Nakahara Shinji , Inoue Akihiko , Hifumi Toru , Okazaki Tomoya , Kikuchi Migaku , Yokobori Shoji , Miyake Yasufumi , Morimura Naoto , Sakamoto Tetsuya , Kuroda Yasuhiro
Published: June 2023

Background

The conflicting results of previous analyses about hypothermia management in patients with out-of-hospital cardiopulmonary arrest have hindered the establishment of a uniform standard temperature setting for temperature control. This study investigated and compared the clinical outcomes of hypothermic (target temperature: 32–34°C) and normothermic (35–36°C) management of out-of-hospital cardiac arrest (OHCA) patients, treated with extracorporeal cardiopulmonary resuscitation (ECPR).

Methods

This secondary analysis of the SAVE-J II study, a retrospective, multicenter, registry study involving 36 participating institutions in Japan, was undertaken, and ECPR patients with a suspected cardiac etiology were included in this cohort. The primary outcome was survival at hospital discharge. Favorable neurological outcomes (5-point Glasgow-Pittsburgh Cerebral Performance Categories 1–2) constituted the secondary outcome. Multivariable logistic analysis, which was adjusted for potential confounders, was performed for the primary and secondary outcomes.

Results

Of the 949 participants of this study, 57% underwent hypothermic management. A total favorable neurological outcome at hospital discharge was identified in 164 patients (17%), and the survival rate was 35%. In multivariable analysis, with the primary and secondary endpoints as each dependent variable, and gender, age, witness, bystander CPR, electrocardiogram, low flow time, and causative disease as categorical covariates, hypothermic management compared to normothermic management in OHCA patients treated with ECPR, was not significantly associated with a favorable neurological outcome (adjusted odds ratio (aOR): 1.22: 95% CI: 0.85–1.74), but was associated with survival (aOR: 1.74: 95% CI: 1.31–2.32).

Conclusions

Compared to normothermic management, hypothermic management of OHCA patients treated with ECPR was not significantly associated with a favorable neurological outcome, but was associated with survival at hospital discharge.
Patterns and outcomes of cardiovascular complications among adult patients with chronic kidney diseases attending Benjamin Mkapa Hospital in Dodoma, Tanzania A protocol of a prospective longitudinal study
Authors: Mbalazi Mohamed , Baraka Alphonce , Meremo Alfred , Meda John
Published: June 2023

Introduction

Chronic Kidney Disease (CKD) affects more than 800 million people globally, the high cardiovascular mortality and morbidity related to CKD result from unique CKD-related risk factors such as anemia and mineral metabolism disturbances and underlying CKD risk factors such as hypertension, diabetes mellitus, and dyslipidemia. The presence of CKD-related structural and functional alterations in the heart and blood vessels increases the risk of hypertension, left ventricular hypertrophy, and heart failure. In advanced CKD stages, the increased risk of hospitalization, heart failure worsening, stroke and death are commonly seen due to increased risk of ischemic heart disease, arrhythmias, and pericarditis.

Methodology

The study will follow a prospective longitudinal design recruiting patients 18 and above years with CKD stage 3 confirmed by estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m2 for the past 3 months, or proteinuria of greater than 200mg/g attending Benjamin Mkapa nephrology and cardiology clinics. Cardiovascular complications will be identified following screening .as per operational definition and a comprehensive baseline assessment. A monthly assessment of cardiovascular complications will be done for a period of 6 months through clinical examinations, imaging and laboratory tests. Cornell and Sokolow-Lyon’s ECG criteria will detect LVH, but ECHO will rule it out. The Framingham criteria will be used to diagnose heart failure. A 12-lead ECG will detect arrhythmias, and an ECG plus cardiac markers will be used to diagnose ischemic heart disease. ECG and ECHO findings of pericardial sac thickening or fluid presence will indicate pericarditis. Continuous and discrete variables will be summarized as mean ±standard deviation (SD), medians, and interquartile ranges, while categorical data will be summarized as frequency and proportion. A binomial logistic regression model will be used to assess the association between independent variables and CVD outcomes
Towards precision well-being in medical education
Authors: Thesen Thomas , Marrero Wesley , Konopasky Abigail , Duncan Matthew , Blackmon Karen
Published: June 2023

Problem

The escalating mental health crisis among medical students is often met with generalized solutions that overlook substantial individual variations. Furthermore, an exclusive focus on mental illness tends to overshadow the necessity of fostering the positive aspects of medical trainee well-being. This Innovation Report introduces a novel, data-driven precision well-being approach for medical education that is built on a more comprehensive and individualized view of mental health.

Approach

Our approach to precision well-being centers on categorizing medical students into distinct and meaningful groups based on their holistic mental health, enabling the future development of tailored wellness support and interventions. We applied k-means clustering, an unsupervised machine learning technique commonly used in precision medicine, to uncover patterns within multidimensional mental health data of medical students. Using data from 3,632 medical students, we formulated our clusters based on recognized metrics for depression, anxiety, and flourishing.

Outcomes

Our analysis identified three distinct clusters, each demonstrating unique patterns along the mental health spectrum. Students in the “Healthy Flourishers” cluster expressed no signs of anxiety or depression and simultaneously reported high levels of flourishing, while students in the “Getting By” cluster reported mild anxiety and depression and diminished flourishing. Students in the “At-Risk” cluster expressed high anxiety and depression, minimal flourishing, and increased suicidality. These results represent an integrated, comprehensive empirical model that classifies individual medical students into distinct well-being categories, creating a way for more personalized mental health support strategies.

Next Steps

The three-cluster model’s generalizability needs to be improved by incorporating longitudinal data from diverse medical student populations. Integrating physiological markers from wearable devices may improve individualized insights. The model can be used to monitor students’ transitions between clusters, determine influencing factors, form individual risk profiles, and evaluate the effectiveness of personalized intervention strategies stratified by cluster membership.
Infection by the lungwormRhabdias pseudosphaerocephalaaffects the expression of immune-related microRNAs by its co-evolved host, the cane toadRhinella marina
Authors: Chan Tsering C. L. , Yagound Boris , Brown Gregory P. , Eyck Harrison J. F. , Shine Richard , Rollins Lee A.
Published: June 2023

Parasites may suppress the immune function of an infected host using microRNAs (miRNAs) to prevent protein production. Nonetheless, little is known about the diversity of miRNAs and their mode(s) of action. In this study, we investigated the effects of infection by a parasitic lungworm (Rhabdias pseudosphaerocephala) on miRNA and mRNA expression of its host, the invasive cane toad (Rhinella marina). We compared miRNA and mRNA expression in naïve toads that had never been infected by lungworms to toads that were infected with lungworms for the first time in their lives, and to toads that were infected the second time in their lives (i.e., had two consecutive infections). In total, we identified 434 known miRNAs and 106 potential novel miRNAs. Compared to uninfected toads, infected animals upregulated five (single-infection treatment) or four (multiple-infection treatment) miRNAs. Seven of these differentially expressed miRNAs were associated with gene pathways related to the immune response, potentially reflecting immunosuppression of cane toads by their parasites. Infected hosts did not respond with substantial mRNA transcription, with only one differentially expressed gene between control and single-infection hosts. Our study suggests that miRNA-mediated interactions may play a role in mediating the interaction between the parasite and its host. Our findings clarify the role of miRNAs in host-parasite interactions, in a system in which an ongoing range expansion by the host has generated substantial divergence in host-parasite interactions.
Prolonging lung cancer response to EGFR inhibition by targeting the selective advantage of resistant cells
Authors: Brunet Lisa , Alexandre David , Lee Jiyoung , Blanquer-Rosselló Maria del Mar , Guernet Alexis , Chhouri Houssein , Kherrouche Zoulika , Arabo Arnaud , Yao Shen , Godefroy David , Dehedin Julie , Li Jian-Rong , Duparc Céline , Jamme Philippe , Vinchent Audrey , Bérard Caroline , Tulasne David , Arena Sabrina , Bardelli Alberto , Cheng Chao , Cho Byoung Chul , Coulouarn Cédric , Aaronson Stuart A. , Cortot Alexis B. , Anouar Youssef , Grumolato Luca
Published: June 2023

Non-small cell lung cancers (NSCLCs) treated with tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) almost invariably relapse in the long term, due to the emergence of subpopulations of resistant cells. Here we show that the lack of sensitivity of these cells to EGFR-TKIs constitutes a vulnerability that can be potentially targeted. Through a DNA barcoding approach, we demonstrate that the clinically approved drug sorafenib specifically abolishes the selective advantage of EGFR-TKI-resistant cells, while preserving the response of EGFR-TKI-sensitive cells, thus resulting in overall inhibition of clonal evolution within the tumor cell mass population. Sorafenib is active against multiple mechanisms of resistance/tolerance to EGFR-TKIs and its effects depend on early inhibition of MAPK interacting kinase (MNK) activity and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and later down-regulation of MCL1 and EGFR. Using several xenograft and allograft models to recapitulate different mechanisms and kinetics of acquired resistance, we show that the sorafenib-EGFR-TKI combination can substantially delay tumor growth and promote the recruitment of inflammatory cells. Together, our findings indicate that sorafenib can substantially prolong the response to EGFR-TKIs by targeting NSCLC capacity to adapt to treatment through the emergence of resistant cells.
Centriole elimination duringC. elegansoogenesis initiates with loss of the central tube protein SAS-1
Authors: Pierron Marie , Woglar Alexander , Busso Coralie , Jha Keshav , Mikeladze-Dvali Tamara , Croisier Marie , Gönczy Pierre
Published: June 2023

Centrioles are lost during oogenesis in most metazoans, ensuring that the zygote is endowed with the correct number of two centrioles, which are paternally contributed. How centriole architecture is dismantled during oogenesis is not understood. Here, we analyze with unprecedent detail the ultrastructural and molecular changes during oogenesis centriole elimination inC. elegans. Centriole elimination begins with loss of the so-called central tube and organelle widening, followed by microtubule disassembly. The resulting cluster of centriolar proteins then disappears gradually, usually moving in a microtubule- and dynein-dependent manner to the plasma membrane. Moreover, we find that neither Polo-like kinases nor the PCM, which modulate oogenesis centriole elimination inDrosophila, do so inC. elegans. Furthermore, we demonstrate that the central tube protein SAS-1 normally departs first from the organelle, which loses integrity earlier insas-1mutants. Overall, our work provides novel mechanistic insights regarding the fundamental process of oogenesis centriole elimination.
Spatiotemporal dynamics of hippocampal-cortical networks underlying the unique phenomenological properties of trauma-related intrusive memories
Authors: Clancy Kevin J. , Devignes Quentin , Ren Boyu , Pollmann Yara , Nielsen Sienna R. , Howell Kristin , Kumar Poornima , Belleau Emily L. , Rosso Isabelle M.
Published: June 2023

Trauma-related intrusive memories (TR-IMs) possess unique phenomenological properties that contribute to adverse post-traumatic outcomes, positioning them as critical intervention targets. However, transdiagnostic treatments for TR-IMs are scarce, as their underlying mechanisms have been investigated separate from their unique phenomenological properties. Extant models of more general episodic memory highlight dynamic hippocampal-cortical interactions that vary along the anterior-posterior axis of the hippocampus (HPC) to support different cognitive-affective and sensory-perceptual features of memory. Extending this work into the unique properties of TR-IMs, we conducted a study of eighty-four trauma-exposed adults who completed daily ecological momentary assessments of TR-IM properties followed by resting-state functional magnetic resonance imaging (rs-fMRI). Spatiotemporal dynamics of anterior and posterior hippocampal (a/pHPC)-cortical networks were assessed using co-activation pattern analysis to investigate their associations with different properties of TR-IMs. Emotional intensity of TR-IMs was inversely associated with the frequency and persistence of an aHPC-default mode network co-activation pattern. Conversely, sensory features of TR-IMs were associated with more frequent co-activation of the HPC with sensory cortices and the ventral attention network, and the reliving of TR-IMs in the “here-and-now” was associated with more persistent co-activation of the pHPC and the visual cortex. Notably, no associations were found between HPC-cortical network dynamics and conventional symptom measures, including TR-IM frequency or retrospective recall, underscoring the utility of ecological assessments of memory properties in identifying the neural substrates of memory properties. These findings provide novel mechanistic insights into the unique features of TR-IMs that are critical for the development of individualized, transdiagnostic treatments for this pervasive, difficult-to-treat symptom.
Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils
Authors: Jeppsson Kristian , Pradhan Biswajit , Sutani Takashi , Sakata Toyonori , Igarashi Miki Umeda , Berta Davide Giorgio , Kanno Takaharu , Nakato Ryuichiro , Shirahige Katsuhiko , Kim Eugene , Björkegren Camilla
Published: June 2023

The Structural Maintenance of Chromosome (SMC) protein complexes cohesin, condensin and the Smc5/6 complex (Smc5/6) are essential for chromosome function. At the molecular level, these complexes fold DNA by loop extrusion. Accordingly, cohesin creates chromosome loops in interphase, and condensin compacts mitotic chromosomes. However, the role of Smc5/6’s recently discovered DNA loop extrusion activity is unknown. Here, we uncover that Smc5/6 associates with transcription-induced positively supercoiled chromosomal DNA at cohesin-dependent chromosome loop boundaries. Mechanistically, single-molecule imaging reveals that dimers of Smc5/6 specifically recognize the tip of positively supercoiled DNA plectonemes, and efficiently initiates loop extrusion to gather the supercoiled DNA into a large plectonemic loop. Finally, Hi-C analysis shows that Smc5/6 links chromosomal regions containing transcription-induced positive supercoiling incis. Altogether, our findings indicate that Smc5/6 controls the three-dimensional organization of chromosomes by recognizing and initiating loop extrusion on positively supercoiled DNA.