bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional anesthesia techniques for cardiac surgery: where are we?
Authors: Kim Rosa S. , Gonzalez-Ciccarelli Luis F. , Brovman Ethan Y. 
Published: July 2022

Purpose of review
Inadequate pain relief after cardiac surgery results in decreased patient experience and satisfaction, increased opioid consumption with its associated adverse consequences, and reduced efficiency metrics. To mitigate this, regional analgesic techniques are an increasingly important part of the perioperative cardiac anesthesia care plan. The purpose of this review is to compare current regional anesthesia techniques, and the relative evidence supporting their efficacy and safety in cardiac surgery.

Recent findings
Numerous novel plane blocks have been developed in recent years, with evidence of improved pain control after cardiac surgery.

Summary
The current data supports the use of a variety of different regional anesthesia techniques to reduce acute pain after cardiac surgery. However, future randomized trials are needed to quantify and compare the efficacy and safety of different regional techniques for pain control after cardiac surgery.
Biologic disease-modifying antirheumatic drugs to treat multisystem inflammatory syndrome in children
Authors: Cron Randy Q. 
Published: July 2022

Purpose of review
Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affecting children. MIS-C shares features with Kawasaki disease (KD) and cytokine storm syndrome (CSS) frequently requiring intensive care support. Although intravenous immunoglobulin (IVIg) and glucocorticoids (GCs) are effective therapeutics for most, refractory MIS-C is treated with various biologic disease-modifying antirheumatic drugs (bDMARDs). Understanding the clinical features, inflammatory cytokines, and genetic associations provides rationale for bDMARD in treating severe MIS-C.

Recent findings
Children with MIS-C have clinical KD features and often present in hypovolemic and cardiogenic shock requiring volume repletion (gastrointestinaI losses) and cardiac pressor support (epinephrine). Investigation of MIS-C serum reveals elevated pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-18, interferon gamma (IFNγ), tumor necrosis factor (TNF)], but to a lesser extent than other established CSS. Gene sequencing of MIS-C children identifies heterozygous mutations in CSS associated genes. Treatment of refractory (IVIg and GC) MIS-C with bDMARDs to IL-1, IL-6, and TNF is efficacious for survival as well as resolving cardiac and coronary artery inflammation.

Summary
MIS-C is a postinfectious complication of SARS-CoV-2 resembling KD and CSS, both genetically and by pro-inflammatory cytokines. MIS-C that is refractory to IVIg and GC is routinely responsive to bDMARDs targeting IL-1, IL-6, and TNF.
Challenges of caring for transgender and gender diverse patients with rheumatic disease: presentation of seven patients and review of the literature
Authors: Mathias Kristen , Mathias Lauren , Amarnani Abhimanyu , Samko Tracey , Lahita Robert G. , Panush Richard S. 
Published: July 2022

Purpose of review
As perspectives on sex and gender identity have evolved, there has been an increase in the practice of transgender medicine. Within rheumatology, however, there is a dearth of information about rheumatic disease in transgender and gender diverse (TGGD) individuals. This is important, as sex hormones affect the etiopathogenesis and expression of autoimmune diseases. We therefore sought to identify TGGD patients with rheumatic disease, review their clinical courses, and appraise existing literature about this population.

Recent findings
Of 1053 patients seen at the Los Angeles County and University of Southern California Medical Center from 2019 through 2021, five transgender men and two transgender women with rheumatic disease were identified. Most patients’ disease courses were not overtly impacted by gender affirming hormone therapy (GAHT). Six of seven patients had psychosocial barriers to care. Our systematic review found 11 studies with 11 transgender women and two transgender men. In 12 of 13 patients, GAHT possibly modulated the patients’ rheumatic disease.

Summary
Our observations suggest GAHT need not be a strict contraindication in TGGD patients with rheumatic disease. TGGD patients often face significant psychosocial barriers. Additional information about this population and empathy toward their health disparities are needed.
A Complement Type to SRS-Schwab Adult Spinal Deformity Classification: The Failure of Pelvic Compensation
Authors: Kwon Ohsang , Lee Sanghoon , Park Sang-Min , Yeom Jin S. , Kim Ho-Joong 
Published: July 2022

Study Design.
Retrospective review.

Objective.
To determine characteristics of patients with adult spinal deformity (ASD) who showed failed pelvic compensation even with significant sagittal imbalance.

Background.
Patients who show failed pelvic compensation despite significant sagittal imbalance reportedly present distinct clinical outcomes. However, to our knowledge, no study has clearly defined or characterized this subgroup of patients with ASD.

Materials and Methods.
We examined 126 patients who underwent reconstructive spinal surgery for ASD between September 2016 and September 2020. Radiographic spinopelvic parameters were assessed. The patients were divided into four quadrant groups based on the two axes of pelvic tilt/pelvic incidence (PT/PI) and the sagittal vertical axis (SVA) with reference to the population median values (0.68 and 147.5 mm, respectively). Patients with low PT/PI and high SVA were considered to have failed pelvic compensation, and they were compared with other patient groups.

Results.
Patients with failed pelvic compensation (low PT/PI and high SVA) had worse clinical outcomes than those with successful pelvic compensation (high PT/PI and high SVA) at one year after surgery. Regarding radiographic outcomes, patients with failed pelvic compensation showed a significantly larger postoperative SVA even after correcting the PI−lumbar lordosis mismatch was corrected to a comparable range with the group of successful pelvic compensation. Notably, patients with failed pelvic compensation showed larger cross-sectional areas of the psoas and back extensor muscles than those with successful pelvic compensation. This suggests that failure of pelvic compensation did not occur because of back muscle weakness, which implies another underlying pathophysiology, including neurological origin.

Conclusion.
Compared with patients with successful pelvic compensation, those with failed pelvic compensation showed lower postoperative improvements in clinical and radiographic outcomes. Therefore, it is important to consider pelvic compensation when planning surgical correction of deformities. Distinct surgical approaches, including overcorrection of the PI−lumbar lordosis mismatch or global sagittal alignment, should be attempted to ensure postoperative symptom improvement.
Chemokines in ICU Delirium: An Exploratory Study
Authors: Smith Ryan J. , Rabinstein Alejandro A. , Cartin-Ceba Rodrigo , Singh Vijay P. , Lachner Christian , Khatua Biswajit , Trivedi Shubham , Gajic Ognjen 
Published: July 2022

OBJECTIVES:
The pathophysiology of delirium is complex and incompletely understood. Inflammation is hypothesized to be integral to its development due to effects on blood brain barrier integrity, facilitation of leukocyte extravasation into brain parenchyma, and propagation of neuroinflammation. Septic shock is the prototypical condition associated with ICU delirium; however, the relative contribution of resultant hypotension and systemic inflammation to the development of delirium is unknown.

DESIGN:
This was a prospective exploratory study.

SETTING:
A multidisciplinary ICU at an academic medical center in Phoenix, AZ.

PATIENTS:
Critically ill patients older than or equal to 18 years old admitted to the ICU.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Screening for delirium was performed using the Confusion Assessment Method for the ICU tool. The levels of C-C motif ligand 2 (CCL2), C-C motif ligand 3, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 10, and interleukin-8 were measured in serum samples obtained within 12 hours of ICU admission. Univariate and multivariate analyses were performed to assess the association of delirium with patient data pertaining to hospital course, laboratory values, vital signs, medication administration, and levels of the aforementioned chemokines. Forty-one of 119 patients (34.5%) in the study cohort developed ICU delirium. Each chemokine studied was associated with delirium on univariate analyses; however, CCL2 was the only chemokine found to be independently associated with the development of delirium on multivariable analysis. The association of increased CCL2 levels with delirium remained robust in various models controlling for age, presence of shock, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation IV score, mean arterial pressure at presentation, lowest mean arterial pressure, and total opioid, midazolam, propofol, and dexmedetomidine exposure.

CONCLUSIONS:
The demonstrated relationship between CCL2 and delirium suggests this chemokine may play a role in the development of delirium and warrants further investigation.
Targeting the DNA damage response beyond poly(ADP-ribose) polymerase inhibitors: novel agents and rational combinations
Authors: Ngoi Natalie Y.L. , Westin Shannon N. , Yap Timothy A. 
Published: July 2022

Purpose of review
Poly(ADP-ribose) polymerase (PARP) inhibitors have transformed treatment paradigms in multiple cancer types defined by homologous recombination deficiency (HRD) and have become the archetypal example of synthetic lethal targeting within the DNA damage response (DDR). Despite this success, primary and acquired resistance to PARP inhibition inevitability threaten the efficacy and durability of response to these drugs. Beyond PARP inhibitors, recent advances in large-scale functional genomic screens have led to the identification of a steadily growing list of genetic dependencies across the DDR landscape. This has led to a wide array of novel synthetic lethal targets and corresponding inhibitors, which hold promise to widen the application of DDR inhibitors beyond HRD and potentially address PARP inhibitor resistance.

Recent findings
In this review, we describe key synthetic lethal interactions that have been identified across the DDR landscape, summarize the early phase clinical development of the most promising DDR inhibitors, and highlight relevant combinations of DDR inhibitors with chemotherapy and other novel cancer therapies, which are anticipated to make an impact in rationally selected patient populations.

Summary
The DDR landscape holds multiple opportunities for synthetic lethal targeting with multiple novel DDR inhibitors being evaluated on early phase clinical trials. Key challenges remain in optimizing the therapeutic window of ATR and WEE1 inhibitors as monotherapy and in combination approaches.
Targeting the methionine−methionine adenosyl transferase 2A−S-adenosyl methionine axis for cancer therapy
Authors: Guo Jiamin , Yang Yanzhong , Buettner Ralf , Rosen Steven T. 
Published: July 2022

Purpose of review
In this review, we summarize the biological roles of methionine, methionine adenosyl transferase 2A (MAT2A) and S-adenosyl methionine (SAM) in methylation reactions during tumorigenesis. Newly emerged inhibitors targeting the methionine−MAT2A−SAM axis will be discussed.

Recent findings
SAM is the critical and global methyl-donor for methylation reactions regulating gene expression, and in mammalian cells, it is synthesized by MAT2A using methionine. Recent studies have validated methionine and MAT2A as metabolic dependencies of cancer cells because of their essential roles in SAM biosynthesis. MAT2A inhibition leads to synthetic lethality in methylthioadenosine-phosphorylase (MTAP)-deleted cancers, which accounts for 15% of all cancer types. Of note, remarkable progress has been made in developing inhibitors targeting the methionine−MAT2A−SAM axis, as the first-in-class MAT2A inhibitors AG-270 and IDE397 enter clinical trials to treat cancer.

Summary
The methionine−MAT2A−SAM axis plays an important role in tumorigenesis by providing SAM as a critical substrate for abnormal protein as well as DNA and RNA methylation in cancer cells. Targeting SAM biosynthesis through MAT2A inhibition has emerged as a novel and promising strategy for cancer therapy.
Actual impact of angiotensin II receptor blocker or calcium channel blocker monotherapy on renal function in real-world patients
Authors: Satoh Michihiro , Hirose Takuo , Satoh Hironori , Nakayama Shingo , Obara Taku , Murakami Takahisa , Muroya Tomoko , Asayama Kei , Kikuya Masahiro , Mori Takefumi , Imai Yutaka , Ohkubo Takayoshi , Metoki Hirohito 
Published: July 2022

Objective:
This observational retrospective cohort study investigates the effect of antihypertensive therapy with angiotensin II receptor blockers (ARBs) or dihydropyridine calcium channel blockers (dCCBs) monotherapy on renal function using longitudinal real-world health data of a drug-naive, hypertensive population without kidney disease.

Methods:
Using propensity score matching, we selected untreated hypertensive participants (n = 10 151) and dCCB (n = 5078) or ARB (n = 5073) new-users based on annual health check-ups and claims between 2008 and 2020. Participants were divided by the first prescribed drug.

Results:
The mean age was 51 years, 79% were men and the mean estimated glomerular filtration rate (eGFR) was 78 ml/min per 1.73 m2. Blood pressure rapidly decreased by approximately 10% in both treatment groups. At the 1-year visit, eGFR levels decreased in the ARB group by nearly 2% but increased in the dCCB group by less than 1%. However, no significant difference was apparent in the annual eGFR change after the 1-year visit. The risk for composite kidney outcome (new-onset proteinuria or eGFR decline ≥30%) was lowest in the ARB group owing to their robust effect on preventing proteinuria: hazard ratio (95% confidence interval) for proteinuria was 0.91 (0.78–1.05) for the dCCB group and 0.54 (0.44–0.65) for the ARB group, compared with that for the untreated group after ending follow-up at the last visit before changing antihypertensive treatment.

Conclusion:
From the present findings based on the real-world data, ARBs can be recommended for kidney protection even in a primary care setting. Meanwhile, dCCB treatment initially increases eGFR with no adverse effects on proteinuria.
Elevated blood pressure in pregnant women with gestational diabetes according to the WHO criteria: importance of overweight
Authors: Birukov Anna , Glintborg Dorte , Schulze Matthias B. , Jensen Tina K. , Kuxhaus Olga , Andersen Louise B. , Kräker Kristin , Polemiti Elli , Jensen Boye L. , Jørgensen Jan S. , Dechend Ralf , Andersen Marianne S. 
Published: July 2022

Objective:
Hypertension before and during early pregnancy has been associated with an increased risk of gestational diabetes mellitus (GDM) in retrospective analyses. We aimed to investigate the prospective blood pressure trackings in a population-based cohort of pregnant women, who were stratified according to their metabolic status in early third trimester.

Methods:
We recorded blood pressure longitudinally during pregnancy in 1230 women from the Odense Child Cohort, Denmark. Fasting glucose and insulin were measured at gestational weeks 28–30. Metabolic status was evaluated according to the WHO 2013 threshold for GDM (GDM-WHO: fasting plasma glucose ≥5.1 mmol/l), insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Relationships between metabolic status in third trimester and blood pressure trajectories were evaluated with adjusted linear mixed models. Trajectory was defined as blood pressure records in pregnancy per 4 weeks interval.

Results:
Prevalence of GDM-WHO was 40% (498/1230). GDM-WHO was associated with 1.46 (0.22–2.70) mmHg higher SBP and 1.04 (0.07–2.01) mmHg higher DBP trajectories in the overall cohort. The associations were driven by differences in the overweight group, with 3.14 (1.05–5.25) mmHg higher SBP and 1.94 (0.42–3.47) mmHg higher DBP per 4 weeks in women with GDM-WHO compared with women without GDM-WHO. GDM-WHO was not associated with blood pressure in women with normal weight. Blood pressure trajectories were elevated across quartiles of insulin resistance.

Conclusion:
GDM-WHO is associated with higher blood pressure in pregnancy, and there appears to be a stronger effect in overweight women.
In Vitro Expansion of Corneal Endothelial Cells for Clinical Application: Current Update
Authors: Hazra Swatilekha , Sneha Iskala V. , Chaurasia Sunita , Ramachandran Charanya 
Published: July 2022

Abstract:
Endothelial dysfunction is one of the leading causes of corneal blindness and one of the common indications for keratoplasty. At present, the standard of treatment involves the replacement of the dysfunctional endothelium with healthy tissue taken from a donor. Because there is a paucity of healthy donor tissues, research on the corneal endothelium has focused primarily on expanding these cells in the laboratory for transplantation in an attempt to reduce the gap between the demand and supply of donor tissues for transplantation. To expand these cells, which are nonmitotic in vivo, various mitogens, substrates, culture systems, and alternate strategies have been tested with varying success. The biggest challenge has been the limited proliferative capacity of these cells compounded with endothelial to mesenchymal transition that alters the functioning of these cells and renders them unsuitable for human transplantation. This review aims to give a comprehensive overview of the most common and successful techniques used in the culture of the cells, the current available evidence in support of epithelial to mesenchymal transition (EMT), alternate sources for deriving the corneal endothelial cells, and advances made in transplantation of these cells.
Increased expression of serum MCP-1, CCL3, IL-6, and IL-17 in patients with vitiligo and IL-17 as a potential clinical marker for active vitiligo
Authors: Zhao Xiaoling , Li Yalan , Li Zihan , Zhang Xiaochong , An Lihui , Sun Yujiao , Liu Dengxiang , Cheng Fang 
Published: July 2022

Objective:
The purpose of this study was to find potential active markers in the progression of vitiligo.

Methods:
We compared 30 healthy controls to 60 patients with vitiligo (30 with active disease and 30 with stable disease) regarding the expression of serum MCP-1, CCL3, CCL5, CCL21, IL-6, and IL-17. Specimens were collected from May 2017 to December 2018. Serological detection was carried out by enzyme-linked immunosorbent assay.

Results:
We found that the serum levels of MCP-1, CCL3, IL-6, and IL-17 were significantly higher in patients with vitiligo than in healthy controls (P < 0.01) and that IL-17 was higher in patients with active vitiligo than in those with stable vitiligo (P < 0.01). After 3 months of treatment, the serum IL-17 level of patients with active vitiligo was not significantly different from that before treatment (P > 0.05); after 6 months of treatment, however, the serum IL-17 level had significantly decreased (P < 0.01).

Conclusions:
These findings suggest that the serum IL-17 level can be used as a marker of vitiligo disease activity, giving it certain guiding significance for clinical treatment.
A novel frameshift CYLD mutation in a family with multiple familial trichoepithelioma
Authors: Yang He-Dan , Wang Xiao-Po 
Published: July 2022

Introduction:
Multiple familial trichoepithelioma is a rare autosomal dominant genodermatosis caused by a mutation in the CYLD gene. This disease is characterized by the development of multiple skin-colored papules and nodules mainly on the central face. We herein describe a family with multiple familial trichoepithelioma with a novel frameshift mutation in CYLD.

Case presentation:
The proband was an 8-year-old girl who presented with a 2-year history of numerous progressive, asymptomatic, firm skin-colored papules on her nasal dorsum, nasolabial folds, and eyelids. Histopathological examination was compatible with the typical findings of trichoepithelioma. Her father displayed similar but inconspicuous smaller lesions on the face. Mutation analysis of the proband identified a heterozygous frameshift mutation c.1181_1182insCTTTGAC (p.D394fs) in exon 10 of CYLD. This mutation was also detected in the proband’s father, but not in either her mother or 100 unrelated control individuals

Discussion:
There is no obvious genotype–phenotype correlation in patients with multiple familial trichoepithelioma. In our study, the girl had a severe clinical appearance characterized by facial disfiguration, whereas her father had inconspicuous smaller lesions despite having the same mutation. We also identified a novel frameshift mutation c.1181_1182insCTTTGAC (p.D394fs) in exon 10 of the CYLD gene. The presence of this mutation leads to premature translation termination and thus to the synthesis of a truncated protein.

Conclusion:
We found a novel frameshift mutation of the CYLD gene in a Chinese family, thus expanding the database of CYLD gene mutations in multiple familial trichoepithelioma.
Lipidomics in nutrition research
Authors: Castro-Alves Victor , Orešič Matej , Hyötyläinen Tuulia 
Published: July 2022

Purpose of review
This review focuses on the recent findings from lipidomics studies as related to nutrition and health research.

Recent findings
Several lipidomics studies have investigated malnutrition, including both under- and overnutrition. Focus has been both on the early-life nutrition as well as on the impact of overfeeding later in life. Multiple studies have investigated the impact of different macronutrients in lipidome on human health, demonstrating that overfeeding with saturated fat is metabolically more harmful than overfeeding with polyunsaturated fat or carbohydrate-rich food. Diet rich in saturated fat increases the lipotoxic lipids, such as ceramides and saturated fatty-acyl-containing triacylglycerols, increasing also the low-density lipoprotein aggregation rate. In contrast, diet rich in polyunsaturated fatty acids, such as n-3 fatty acids, decreases the triacylglycerol levels, although some individuals are poor responders to n-3 supplementation.

Summary
The results highlight the benefits of lipidomics in clinical nutrition research, also providing an opportunity for personalized nutrition. An area of increasing interest is the interplay of diet, gut microbiome, and metabolome, and how they together impact individuals’ responses to nutritional challenges.